Hi Elaine, my name is Claire and I am 26 yrs old and also from Ireland.  I have
had Miyoshi for 7-8 years now but it was only in the past 3-4 yrs were it has
really affected me as i showed no signs when i was dignosed.  I only have it in
my legs and am sorry to hear it is in your back and arms as i think my arms are
getting weaker especially my wrists. I have visit my Neurologist at belfast City
Hospital once a year but if dont give me any advice or support apart from naggin
me about my weight which over the past 2 years just seems to be increasing
beyond my control.

I resorted to using a wheelchair firstly about 3 years ago just on holidays and
shopping trips but have now been using it full time for just over 2 years due to
falling and breaking my right foot more than 8 times on seperate occassions as i
used to use a stick just before that.  I have discovered that this site is a
good support network as we are all going through the same in one way or another
and its good to chat with people who actually understand what your talking about
instead of continually having to explain to them.

Also regarding kids (which i dont have yet!!) they would only get it if both you
and your husband were carriers.

All the best, Claire xx

--- In dysferlin@yahoogroups.com, Elaine Byrne <ebd197@...> wrote:
>
> Hi Folks,
>
> My name is Elaine and I'm 35 years old from Ireland.  I wrote on this website
months ago and it totally knocked me for six the stories i was reading about
people.  I am currently awaiting genetic testing results from Newcastle,
England.  Tests so far have shown the Dysferlin but i am waiting for a 100%
diagnosis.  I come from a family of 4.  I have 2 brothers and one sister and
all them are fit as fiddles.  I myself was a very fit, active girl until I
first noticed muscle weakness in the legs at the age of 24 and have slowly been
getting worse.  It has now spead to my arms and back.  My Neurologist in
Dublin has told me that there is no-one else in Ireland that he knows of with
this dysferlinopathy.  So i'm a guenipig for them now.  One part of the
Genetic Testing came back saying that the FKRP Gene Mutation was negative.  Can
anyone tell me what this means, is it a good thing or a bad thing???.  I don't
want to look up anything because it
>  only gets me down what i have been reading. My Neurologist wants me to wait
until all genetic testing is done and then he will meet with myself and my
hubby. 
> I am working fulltime at the moment in a clinic for disabled children.  I
notice alot of peple cannot go up on tip toe.  I can for now.  This disease
really gets to me at times and my biggest fear is ending up in a wheelchair. 
That's what knocked me for six when i started reading people's stories.  i had
to turn off the computer for weeks.
> Myself and my hubby currently have no kids and am terrified to have one in
case they end up like me.  Can anyone ease my mind about this. 
> I think you are all so brave with coping with this terrible illness, i have
good days and bad days but the fear is of getting worse.......
>
> take care for now.
> Elaine.
>
>
>
>
> ________________________________
> From: baw1064 <bwilliams163@...>
> To: dysferlin@yahoogroups.com
> Sent: Thu, November 12, 2009 6:51:23 PM
> Subject: [dysferlin] Re: A reintroduction and a question...
>
>  
> Hi Bryan,
>
> Just a quick comment on your diagnosis. It is possible for Miyoshi to be
caused by mutations in other genes besides dysferlin, there are at least two
other genes that have been reported in the literature (one identified, the other
not yet identified, but its location in the genome is known pretty accurately).
It's also possible that dysferlin might show up on a blood tests (a mutation
doesn't necessarily mean a person won't have any of the protein) but isn't able
to function properly in muscle.
>
> Did your doctor have any thoughts on what the next step in a diagnosis should
be?
>
> Best wishes,
> Brad
>
> --- In dysferlin@yahoogrou ps.com, "b5sense" <b5sense@ > wrote:
> >
> > Hello everybody,
> > It's been a while since I posted anything so I figured I'd reintroduce
myself. I'm Bryan Nickell. I just turned thirty and was diagnosed with Miyoshi
Myopathy about six years ago. It is doing a pretty good number on my calf
muscles, my left being smaller than my right. I wear Blue Rocker Toe Off braces
which are pretty uncomfortable but give me enough support that I can be somewhat
active. I was an athlete my whole life so I'm having to get used to this new
body that I have. I just got married about two months ago and my wife and I own
our own business which is an old fashioned soda fountain and retail store in
North Carolina.
> >
> > I was writing because I had a question for people in the group. My doctor is
confident (with what they know now) with my Miyoshi diagnosis, but a blood test
that was done at the Mayo Clinic found that I do have the dysferlin protein. I
was wondering if this was true for anybody else in the group? My doctor said it
was rare to have Miyoshi that presented itself like this, but I was hoping maybe
somebody else out there has had the same experience as me. It can be pretty
lonely trying to cope with a disease like this that many people don't seem to
understand.
> >
> > Thanks for responding if you do, and if not I just want everyone to know
that it is a great comfort knowing y'all are out there. I am not happy that any
of us have these diseases, but I feel grateful that we all have each other. I
hope everyone is doing well and I look forward to hearing from you.
> >
> > Thanks again,
> > Bryan Nickell
> >
>

Hi Elain

--- In dysferlin@yahoogroups.com, Elaine Byrne <ebd197@...> wrote:
>
> Hi Folks,
>
> My name is Elaine and I'm 35 years old from Ireland.  I wrote on this website
months ago and it totally knocked me for six the stories i was reading about
people.  I am currently awaiting genetic testing results from Newcastle,
England.  Tests so far have shown the Dysferlin but i am waiting for a 100%
diagnosis.  I come from a family of 4.  I have 2 brothers and one sister and
all them are fit as fiddles.  I myself was a very fit, active girl until I
first noticed muscle weakness in the legs at the age of 24 and have slowly been
getting worse.  It has now spead to my arms and back.  My Neurologist in
Dublin has told me that there is no-one else in Ireland that he knows of with
this dysferlinopathy.  So i'm a guenipig for them now.  One part of the
Genetic Testing came back saying that the FKRP Gene Mutation was negative.  Can
anyone tell me what this means, is it a good thing or a bad thing???.  I don't
want to look up anything because it
>  only gets me down what i have been reading. My Neurologist wants me to wait
until all genetic testing is done and then he will meet with myself and my
hubby. 
> I am working fulltime at the moment in a clinic for disabled children.  I
notice alot of peple cannot go up on tip toe.  I can for now.  This disease
really gets to me at times and my biggest fear is ending up in a wheelchair. 
That's what knocked me for six when i started reading people's stories.  i had
to turn off the computer for weeks.
> Myself and my hubby currently have no kids and am terrified to have one in
case they end up like me.  Can anyone ease my mind about this. 
> I think you are all so brave with coping with this terrible illness, i have
good days and bad days but the fear is of getting worse.......
>
> take care for now.
> Elaine.
>
>
>
>
> ________________________________
> From: baw1064 <bwilliams163@...>
> To: dysferlin@yahoogroups.com
> Sent: Thu, November 12, 2009 6:51:23 PM
> Subject: [dysferlin] Re: A reintroduction and a question...
>
>  
> Hi Bryan,
>
> Just a quick comment on your diagnosis. It is possible for Miyoshi to be
caused by mutations in other genes besides dysferlin, there are at least two
other genes that have been reported in the literature (one identified, the other
not yet identified, but its location in the genome is known pretty accurately).
It's also possible that dysferlin might show up on a blood tests (a mutation
doesn't necessarily mean a person won't have any of the protein) but isn't able
to function properly in muscle.
>
> Did your doctor have any thoughts on what the next step in a diagnosis should
be?
>
> Best wishes,
> Brad
>
> --- In dysferlin@yahoogrou ps.com, "b5sense" <b5sense@ > wrote:
> >
> > Hello everybody,
> > It's been a while since I posted anything so I figured I'd reintroduce
myself. I'm Bryan Nickell. I just turned thirty and was diagnosed with Miyoshi
Myopathy about six years ago. It is doing a pretty good number on my calf
muscles, my left being smaller than my right. I wear Blue Rocker Toe Off braces
which are pretty uncomfortable but give me enough support that I can be somewhat
active. I was an athlete my whole life so I'm having to get used to this new
body that I have. I just got married about two months ago and my wife and I own
our own business which is an old fashioned soda fountain and retail store in
North Carolina.
> >
> > I was writing because I had a question for people in the group. My doctor is
confident (with what they know now) with my Miyoshi diagnosis, but a blood test
that was done at the Mayo Clinic found that I do have the dysferlin protein. I
was wondering if this was true for anybody else in the group? My doctor said it
was rare to have Miyoshi that presented itself like this, but I was hoping maybe
somebody else out there has had the same experience as me. It can be pretty
lonely trying to cope with a disease like this that many people don't seem to
understand.
> >
> > Thanks for responding if you do, and if not I just want everyone to know
that it is a great comfort knowing y'all are out there. I am not happy that any
of us have these diseases, but I feel grateful that we all have each other. I
hope everyone is doing well and I look forward to hearing from you.
> >
> > Thanks again,
> > Bryan Nickell
> >
>

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Tuesday, November 17, 2009 12:00 PM
To: dysferlin@yahoogroups.com
Subject: RE: [dysferlin] reinventing the wheel?

 

hey Josh.
dont now if you know that accelleron already compleeted phase 1 study for the same or maybe beefed up compounds, as the mda grantees do. that's in healthy humans in montreal.

http://www.acceleronpharma.com/content/news/press-releases/detail.jsp/q/news-id/122
you participate in the early studies dint you?
maybe i am wrong.

i posted the links here a few months ago.
another  company has something simmilar but for animals.

http://www.metamorphixinc.com/research1.html

http://www.albertapork.com/news.aspx?NavigationID=1477

if you search enough you can find myostatin antibodys for sale only to qualified people.
and you think the elite athletes they get there with meat and potatoes and lifting dumbbells?
do you remember  the Balco case?
http://www.ergogenics.org/120.html#7b
there probably a multiple of them. 

now to the point.
why they are doing experiments that they are already done to prove something that's proven?
and that's my tow drachmas...
 

---

To: dysferlin@yahoogroups.com
From: jthayer@eapdlaw.com
Date: Tue, 17 Nov 2009 11:12:15 -0500
Subject: RE: [dysferlin] reinventing the wheel?

 

Matt,

 

Thank you for the Science Daily link.  That is very interesting and encouraging in my opinion.

 

Could you explain why you consider what Dr. Mendell is doing to be a waste of money and duplicative of other research?  Is it because it is only one of several potential ways to inhibit myostatin, such as gene therapy, antibodies and small compounds?  Since no single method of inhibiting myostatin has yet to show efficacy in human patients with neuromuscular disorders, why do you think pursuing muliple approaches is duplicative?

 

That's not a rhetorical question.  There may be some other point you are trying to make, but it's hard to read minds.  :-)

 

Josh

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Tuesday, November 17, 2009 9:57 AM
To: dysferlin@yahoogroups.com
Subject: [dysferlin] reinventing the wheel?

 

don't want to discount the abilities and the efforts of dr Campbells lab, but it seems to me like reinventing the wheel here? maybe waste of money?

http://www.sciencedaily.com/releases/2009/11/091113132251.htm

there is probably underground labs  that they do full production of these compounds for extreme
athletes by now...

in another note tell me if you are still complaining after you see this:

http://www.youtube.com/watch?v=pcctg0esEQE&feature=related

_______________________
Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ, New York NY, Newport Beach CA, Providence RI, Stamford CT, Washington DC, West Palm Beach FL, Wilmington DE, London UK, Hong Kong (associated office)
CONFIDENTIALITY NOTICE
This e-mail message from Edwards Angell Palmer & Dodge LLP and Edwards Angell Palmer & Dodge UK LLP is intended only for the individual or entity to which it is addressed. This e-mail may contain information that is privileged, confidential and exempt from disclosure under applicable law. If you are not the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you received this e-mail by accident, please notify the sender immediately and destroy this e-mail and all copies of it. We take steps to protect against viruses but advise you to carry out your own checks and precautions as we accept no liability for any which remain. We may monitor emails sent to and from our server(s) to ensure regulatory compliance to protect our clients and business.
Edwards Angell Palmer & Dodge UK LLP is a limited liability partnership registered in England (registered number OC333092) and is regulated by the Solicitors Regulation Authority. A list of members' names and their professional qualifications may be inspected at our registered office, One Fetter Lane, London EC4A 1JB, UK, telephone +44 207 583 4055.
Disclosure Under U.S. IRS Circular 230: Edwards Angell Palmer & Dodge LLP informs you that any tax advice contained in this communication, including any attachments, was not intended or written to be used, and cannot be used, for the purpose of avoiding federal tax related penalties or promoting, marketing or recommending to another party any transaction or matter addressed herein.
 

A brief description on myostatin, etc. to try to make the discussion
understandable to everyone.

Myostatin is a protein that is a negative regulator of muscle growth, which
basically means less myostatin -> more muscle.  Why would the body have a
protein that does this?  Basically having more muscle means you have to eat more
food, so for critters out in the wild having more muscle isn't necessarily
advantageous if food is in limited supply.

There are animals known that lack myostatin (cattle, mice, and one human) that
have LOTS of muscle and don't seem to have any health problems.

It turns out there are many proteins involved in regulating muscle growth.  It's
very complicated and not yet thoroughly understood.  Follistatin is a negative
regulator of myostatin (more follistatin -> less myostatin -> more muscle),
which is why Dr. Mendell's lab tried to put extra copies of the follistatin gene
into the mouse model.

The Jain Foundation is funding a project by Se-jin Lee (Johns Hopkins), whose
lab discovered myostatin.  A brief write-up of his presentation is given on page
20 of the conference summary document.

It appears that the exact way that muscle growth is regulated in mice is
somewhat different than in humans. The same genes/proteins are involved, but the
quantitative effects are somewhat different.  For instance, mice have a lot more
myostatin than humans, so testing a drug on mice to see how much muscle growth
is increased and then trying that same amount on humans doesn't quite work.

If you google "myostatin inhibitor" there will be a lot of hits for things that
claim to do this--I'm very skeptical until I see some evidence from a controlled
study.

There was a clinical trial on myostatin inhibition conducted by Wyeth a few
years ago.  No effect of the compound was found, but there are a couple of
reasons for that.  The study gradually tried patients on increasing doses, to
verify safety, then to look for a therapeutic effect.  One of the patients had a
side effect (a stomach ache, if I remember correctly) which was an "adverse
event" and halted the trial, before a dosage that was liable to have an
observable effect was ever reached.  Also, because humans have much lower levels
of myostatin than mice, it wasn't possible to actually monitor myostatin levels
to see if the drug was reducing them, as could be done in mice.

Brad

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Tuesday, November 17, 2009 9:57 AM
To: dysferlin@yahoogroups.com
Subject: [dysferlin] reinventing the wheel?

 

don't want to discount the abilities and the efforts of dr Campbells lab, but it seems to me like reinventing the wheel here? maybe waste of money?

http://www.sciencedaily.com/releases/2009/11/091113132251.htm

there is probably underground labs  that they do full production of these compounds for extreme
athletes by now...

in another note tell me if you are still complaining after you see this:

http://www.youtube.com/watch?v=pcctg0esEQE&feature=related

_______________________
Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ, New York NY, Newport Beach CA, Providence RI, Stamford CT, Washington DC, West Palm Beach FL, Wilmington DE, London UK, Hong Kong (associated office)

CONFIDENTIALITY NOTICE
This e-mail message from Edwards Angell Palmer & Dodge LLP and Edwards Angell Palmer & Dodge UK LLP is intended only for the individual or entity to which it is addressed. This e-mail may contain information that is privileged, confidential and exempt from disclosure under applicable law. If you are not the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you received this e-mail by accident, please notify the sender immediately and destroy this e-mail and all copies of it. We take steps to protect against viruses but advise you to carry out your own checks and precautions as we accept no liability for any which remain. We may monitor emails sent to and from our server(s) to ensure regulatory compliance to protect our clients and business.

Edwards Angell Palmer & Dodge UK LLP is a limited liability partnership registered in England (registered number OC333092) and is regulated by the Solicitors Regulation Authority. A list of members' names and their professional qualifications may be inspected at our registered office, One Fetter Lane, London EC4A 1JB, UK, telephone +44 207 583 4055.

Disclosure Under U.S. IRS Circular 230: Edwards Angell Palmer & Dodge LLP informs you that any tax advice contained in this communication, including any attachments, was not intended or written to be used, and cannot be used, for the purpose of avoiding federal tax related penalties or promoting, marketing or recommending to another party any transaction or matter addressed herein.

 

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Tuesday, November 17, 2009 10:56 AM
To: dysferlin@yahoogroups.com
Subject: RE: [dysferlin] reinventing the wheel?

 

to whom it may concern..
and its Dr. Mendell
not cambell. my mistake

---

To: dysferlin@yahoogroups.com
From: jthayer@eapdlaw.com
Date: Tue, 17 Nov 2009 10:44:48 -0500
Subject: RE: [dysferlin] reinventing the wheel?

 

Matt,

 

Whom exactly are you addressing?  Me?  Brad?  The group?

 

Who is complaining?  About what?

 

I'll email you off line once I look at the links.

 

Josh

 

 

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Tuesday, November 17, 2009 9:57 AM
To: dysferlin@yahoogroups.com
Subject: [dysferlin] reinventing the wheel?

 

don't want to discount the abilities and the efforts of dr Campbells lab, but it seems to me like reinventing the wheel here? maybe waste of money?

http://www.sciencedaily.com/releases/2009/11/091113132251.htm

there is probably underground labs  that they do full production of these compounds for extreme
athletes by now...

in another note tell me if you are still complaining after you see this:

http://www.youtube.com/watch?v=pcctg0esEQE&feature=related

_______________________
Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ, New York NY, Newport Beach CA, Providence RI, Stamford CT, Washington DC, West Palm Beach FL, Wilmington DE, London UK, Hong Kong (associated office)
CONFIDENTIALITY NOTICE
This e-mail message from Edwards Angell Palmer & Dodge LLP and Edwards Angell Palmer & Dodge UK LLP is intended only for the individual or entity to which it is addressed. This e-mail may contain information that is privileged, confidential and exempt from disclosure under applicable law. If you are not the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you received this e-mail by accident, please notify the sender immediately and destroy this e-mail and all copies of it. We take steps to protect against viruses but advise you to carry out your own checks and precautions as we accept no liability for any which remain. We may monitor emails sent to and from our server(s) to ensure regulatory compliance to protect our clients and business.
Edwards Angell Palmer & Dodge UK LLP is a limited liability partnership registered in England (registered number OC333092) and is regulated by the Solicitors Regulation Authority. A list of members' names and their professional qualifications may be inspected at our registered office, One Fetter Lane, London EC4A 1JB, UK, telephone +44 207 583 4055.
Disclosure Under U.S. IRS Circular 230: Edwards Angell Palmer & Dodge LLP informs you that any tax advice contained in this communication, including any attachments, was not intended or written to be used, and cannot be used, for the purpose of avoiding federal tax related penalties or promoting, marketing or recommending to another party any transaction or matter addressed herein.
 

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Tuesday, November 17, 2009 9:57 AM
To: dysferlin@yahoogroups.com
Subject: [dysferlin] reinventing the wheel?

 

don't want to discount the abilities and the efforts of dr Campbells lab, but it seems to me like reinventing the wheel here? maybe waste of money?

http://www.sciencedaily.com/releases/2009/11/091113132251.htm

there is probably underground labs  that they do full production of these compounds for extreme
athletes by now...

in another note tell me if you are still complaining after you see this:

http://www.youtube.com/watch?v=pcctg0esEQE&feature=related

_______________________
Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ, New York NY, Newport Beach CA, Providence RI, Stamford CT, Washington DC, West Palm Beach FL, Wilmington DE, London UK, Hong Kong (associated office)

CONFIDENTIALITY NOTICE
This e-mail message from Edwards Angell Palmer & Dodge LLP and Edwards Angell Palmer & Dodge UK LLP is intended only for the individual or entity to which it is addressed. This e-mail may contain information that is privileged, confidential and exempt from disclosure under applicable law. If you are not the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you received this e-mail by accident, please notify the sender immediately and destroy this e-mail and all copies of it. We take steps to protect against viruses but advise you to carry out your own checks and precautions as we accept no liability for any which remain. We may monitor emails sent to and from our server(s) to ensure regulatory compliance to protect our clients and business.

Edwards Angell Palmer & Dodge UK LLP is a limited liability partnership registered in England (registered number OC333092) and is regulated by the Solicitors Regulation Authority. A list of members' names and their professional qualifications may be inspected at our registered office, One Fetter Lane, London EC4A 1JB, UK, telephone +44 207 583 4055.

Disclosure Under U.S. IRS Circular 230: Edwards Angell Palmer & Dodge LLP informs you that any tax advice contained in this communication, including any attachments, was not intended or written to be used, and cannot be used, for the purpose of avoiding federal tax related penalties or promoting, marketing or recommending to another party any transaction or matter addressed herein.

 

The publication reference is

Stem Cells. 2004;22(6):981-93.

Human umbilical cord blood cells differentiate into muscle in sjl muscular
dystrophy mice.
Kong KY, Ren J, Kraus M, Finklestein SP, Brown RH Jr.


The full test of the article is available on pubmed for free :-)



--- In dysferlin@yahoogroups.com, "Thayer, Joshua" <jthayer@...> wrote:
>
> Hi Matt,
>
> I will check to see if the cord blood study results were published by
> Dr. Brown's lab at M.G.H..  I believe so.  I'll look into it and send
> you a link or pdf.
>
> I agree on the muscle biopsy position.  I'm done giving pieces of
> myself.  Well, there's not a lot more left anyway!
>
> Also, I have been taking similar supplements and following a diet rich
> in fruits, vegetables, grains and fish.  I also do physical therapy
> three times a week.  I can't say it necessarily slows down the
> progression, but you never know.  And it does make me feel more healthy
> and energic, so it's a good idea regardless.
>
> Regards,
>
> Josh
>
> P.S.  There certainly are too many lawyers in the United States, but not
> too many good lawyers.  :-)
>
>
> ________________________________
>
>  From: dysferlin@yahoogroups.com
> [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
>  Sent: Monday, November 16, 2009 11:20 AM
>  To: dysferlin@yahoogroups.com
>  Subject: RE: [dysferlin] Re: Organizing a natural history study
> on dysferlin
>
>
>
>
>  I congratulate you and thank you for your efforts towards a
> treatment.
>  i dint realize that you were involved in to that extend in
> trying to help.
>  i think of lawyers as overpaid pencil pushers and ambulant
> chasers. (just kidding
> <http://gfx2.hotmail.com/mail/w4/pr01/ltr/emoticons/smile_regular.gif> )
>
>  i gave one muscle biopsy and that's it. i like to preserve what
> ever i have left.
>  i still walk on my 49th year, but with extra help from healthy
> diet lots of sun (when available) some creatine, co q10, curcumin etc
>
>
>  any published papers from the study?
>
>
>  George Carpati unfortunately died a think last year. he was a
> genius in his field.
>  hope somebody can follow up on where he left.
>  thanks
>  mathew
>
>
> ________________________________
>
>  To: dysferlin@yahoogroups.com
>  From: jthayer@...
>  Date: Mon, 16 Nov 2009 10:31:48 -0500
>  Subject: RE: [dysferlin] Re: Organizing a natural history study
> on dysferlin
>
>
>
>  Matt,
>
>  As I understand it, there may still be a potential for
> Myoblasts.  I know that at least one doctor up in Quebec designed
> studies back in the 1990s that seemed to fail, but he still believes in
> the approach and thinks the studies were misinterpreted, or not done
> correctly, or something.  I understand that Health Canada may be holding
> up further work in the area for now.  Note that any myoblast approach
> means living on an immune suppressant for the rest of your life.  More
> money to big pharma for that!  It would also mean ongoing IV
> administrations at best.
>
>  With respect to stem cells, my family and friends and I
> sponsored a cord blood stem cell study in mice in 2000 - 2002 or so at
> M.G.H.  Unfortunately, the results were not very promising.  As I
> understand it, some full length dysferlin protein was expressed in the
> skeletal muscles of the mice after the cord blood stems cells were
> administered, but not a clinically significant amount.  The study went
> on for a few years after our funding commitment (on NIH and MDA funding
> I think) to try to improve the results, but was eventually abandoned.
> At least for now.  These things tend to come and go as new things are
> discovered that may be relevant.
>
>  I do not know enough about the applicability of embryonic stem
> cells, but I am not opposed to their use if warranted by science.  I
> believe that Brad, who is far more knowledgeable than I am with respect
> to the biology behind all of this, posted about embryonic stems cells
> some time ago in response to one of your posts.
>
>  I did not intentionally omit any reference to myoblasts or stem
> cells (embryonic or adult) in my earlier post, and Brad has discussed
> them before.  In any event, yes, they are potential treatments and all
> the more reason to register with the Jain Foundation.
>
>  You are a realist, fine.  So am I.  I was diagnosed 22 years
> ago.  I have participated in 2 clinical trials (gentamicin and Myo-29),
> I have given 5 open muscle biopsies, several needle biopsies and
> countless blood draws for scientific research.  I have no idea when or
> if the efforts I have made will bear fruit.  I choose to contribute
> time, money, blood and tissue samples even though I remain skeptical and
> frustrated a lot of the time.  I totally support efforts in other
> countries, and in particular India, and I know the Jain Foundation does
> too.  You seem to think the rest of us live in la la land, or at least
> that is a reasonable inference from some of your posts.  That
> characterization is incorrect.  You have dysferlinopathy I understand,
> and yet are still quite mobile?  Believe me, you will become no less of
> a realist as the years go by and you slowly lose that mobility.
>
>  So, Matt, have you registered as a patient with the Jain
> Foundation?  I cannot ask them, of course, and you can tell me to "piss
> off "if you want, but I registered immediately when I knew it was
> possible, and I hope you and all others with the condition who read this
> will too.
>
>  Josh
>
>
>
>
> ________________________________
>
> 	 From: dysferlin@yahoogroups.com
> [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
> 	 Sent: Monday, November 16, 2009 8:30 AM
> 	 To: dysferlin@yahoogroups.com
> 	 Subject: RE: [dysferlin] Re: Organizing a natural
> history study on dysferlin
>
>
>
> 	 by any means, i don't want to discourage people to come
> forward and participate to any approach that facilitates a potential
> therapy or treatment.
> 	 my frustration with the attitude of the big pharma comes
> out sometimes in light of events like the swine flue.
> 	 if there is no profit on the bottom line, there would be
> no participation of the ones that they own the
> 	 medical centers, universities, governments etc.
> 	 and if somebody comes up with a good idea for a
> potential treatment, eventually will find a wall of impedance from
> these.
> 	 we just have to settle for crams. I am not living in
> lala land, i am a realist.
> 	 look at acceleron.  (ace 31 etc) i am pretty sure that
> compound would potentially help lots of us.
> 	 but they waiting until they have something that could be
> marketed to the main stream. (i can read the head lines. "a cure for fat
> peopple" accelerons IPO at 50$ a share)...
>
> 	 you guys dint mention Myoblasts, or stem cells...whats
> up with that?
> 	 if i remember somebody here had an experience with
> myoblasts.
> 	 the cost i think is prohibitive.
>
> 	 i put my bets on India. if something comes will come
> from there.
> 	 lots more lgmd patients and doctors that have some
> altruism in them.
> 	 they just need some help from big pharma...
> 		  Mathew
>
>
>
>
>
>
> ________________________________
>
> 	 To: dysferlin@yahoogroups.com
> 	 From: bwilliams163@...
> 	 Date: Mon, 16 Nov 2009 05:04:49 +0000
> 	 Subject: [dysferlin] Re: Organizing a natural history
> study on dysferlin
>
>
> 	 Josh is very knowledgable about the economics and
> approval process. I'll just add a little bit to his post.
>
> 	 Besides "dysferlin-specific custom therapies" a brand
> new drug specifically designed to treat dysferlin deficiency, there are
> three general categories of drugs where the economics are more
> favorable.
>
> 	 1) drugs that are designed to treat a specific type of
> mutation--in theory they should work for a mutation in any gene,
> although there's the question of how much protein would be needed for a
> therapeutic effect, and there may be side effects that are gene
> specific. PTC-124 is in this category.
>
> 	 2) drugs that promote muscle growth, that may be
> beneficial for any type of muscular dystrophy. Drugs that inhibit
> myostatin (one was tested by Wyeth a while back) and therefore promote
> muscle growth are in this category.
>
> 	 3) drugs that are already approved for some completely
> different use having nothing to do with muscular dystrophy. Before
> PTC-124 was developed, another compound, gentomycin, which is approved
> as an antibiotic, was found to have some effect (less than PTC-124) in
> the same way. These already approved drugs will have to be tested in
> animals first, and will need a fairly large-scale screening to try to
> find one that works. In this case, there's not a safety issue (the drug
> is already approved) but one would have to show that it works.
>
> 	 --- In dysferlin@yahoogroups.com
> <mailto:dysferlin@yahoogroups.com> , "Thayer, Joshua" <jthayer@>
> wrote:
> 	 >
> 	 > Matthew,
> 	 >
> 	 > You are correct that a compound that only targets the
> dysferlin protein
> 	 > probably will not be of interest to big pharma. It is
> possible that it
> 	 > would, because if the pharma company gets orphan drug
> status from the
> 	 > FDA for the compound, it can charge a lot of money per
> patient and
> 	 > obtain reimbursement. That possibility will be
> increased, of course, if
> 	 > there is proof of at least some critical mass of
> dysferlin deficient
> 	 > patients. But let's assume that that won't happen.
> 	 >
> 	 > Even so, the "by products" you describe could be
> extremely important,
> 	 > and our access to them could be facilitated by this
> proposed study. For
> 	 > example, Ataluren (PTC 124) is currently in Duschenne
> Dystrophy, Cystic
> 	 > Fibrosis and Hemophilia trials. Assuming Ataluren does
> not fail (which
> 	 > it might), it is of course possible that it will be
> approved in one or
> 	 > all of those other conditions, and quickly enough to
> be available off
> 	 > label for those of us with a nonsense mutation. But it
> is also possible
> 	 > that the FDA will want to see it tested in
> Dysferlinopathy and other
> 	 > conditions linked to such mutations. And, unless
> approved for
> 	 > dysferlinopathy, it might not be covered by insurance
> for us.
> 	 >
> 	 > Also, imagine an approach that generally repairs
> damaged muscle fiber
> 	 > notwithstanding the missing protein (or other factor)
> that requires
> 	 > faster and more thorough repair to avoid cell death.
> If this Natural
> 	 > History Study can be done, then at least we with
> Miyoshi Myopathy and
> 	 > LGMDIIB will have a shot at being included in a trial,
> which might
> 	 > provide some therapeutic value prior to approval.
> 	 >
> 	 > I understand your frustration with big pharma, and
> although you have
> 	 > blasted me before on an earlier exchange, you will
> have to trust me that
> 	 > I share your frustration. But I do hope that you are
> not trying to
> 	 > discourage people from participating in this important
> study to make a
> 	 > political point, and I hope you will participate as
> well.
> 	 >
> 	 > Josh
> 	 >
> 	 >
> 	 > ________________________________
> 	 >
> 	 > From: dysferlin@yahoogroups.com
> <mailto:dysferlin@yahoogroups.com>
> 	 > [mailto:dysferlin@yahoogroups.com
> <mailto:dysferlin@yahoogroups.com> ] On Behalf Of MATHEW anas
> 	 > Sent: Sunday, November 15, 2009 11:01 PM
> 	 > To: dysferlin@yahoogroups.com
> <mailto:dysferlin@yahoogroups.com>
> 	 > Subject: RE: [dysferlin] Organizing a natural history
> study on
> 	 > dysferlin
> 	 >
> 	 >
> 	 >
> 	 >
> 	 > I am wondering if any pharmaceutical company would be
> interest
> 	 > in to any trial that involves couple hundred people
> where the potential
> 	 > of profits are virtually none.
> 	 > If we get any treatments IMHO would be as a
> "byproduct" of
> 	 > treatments of other disorders more "main stream".
> 	 > the doctors and the big pharma are more interest to
> lining their
> 	 > pockets than anything.
> 	 > (look at the h1n1 example...)
> 	 > Hope i am wrong.
> 	 > Mathew
> 	 >
> 	 > ________________________________
> 	 >
> 	 > To: dysferlin@yahoogroups.com
> <mailto:dysferlin@yahoogroups.com>
> 	 > From: bwilliams163@
> 	 > Date: Mon, 16 Nov 2009 03:41:55 +0000
> 	 > Subject: [dysferlin] Organizing a natural history
> study on
> 	 > dysferlin
> 	 >
> 	 >
> 	 > At the Jain Foundation conference this past summer,
> one of the
> 	 > topics discussed at a satellite meeting was how to
> organize and conduct
> 	 > a natural history study on dysferlin deficiency.
> 	 >
> 	 > I've posted a synopsis of the conference in the files
> section of
> 	 > the groups page. The first page summarizes the natural
> history sattelite
> 	 > meeting.
> 	 >
> 	 > Why do a natural history study? There are a few
> reasons. One is
> 	 > to provide the infrastructure for future clinical
> trials. In order to
> 	 > conduct a clinical trial of some proposed treatment,
> one needs some
> 	 > simple measurement which will be able to tell if the
> treatment is
> 	 > effective. Knowing the typical rate of progression of
> dysferlin
> 	 > deficiency in the absence of treatment, or details
> about diagnostic
> 	 > tests such as MRIs, will be needed before a clinical
> trial can be
> 	 > started.
> 	 >
> 	 > Another is simply to have enough patients identified,
> and enough
> 	 > clinical centers involved in dysferlin research, that
> it is possible to
> 	 > conduct a clinical trial. If there aren't enough
> patients (a minimum
> 	 > will probably be at least 100), you can't do a
> clinical trial no matter
> 	 > how good an idea you have for a treatment.
> 	 >
> 	 > It's generally acknowledged that a natural history
> study will
> 	 > have to be done before a clinical trial will be
> possible. So even though
> 	 > a natural history study won't directly benefit
> patients, it has to
> 	 > happen before trials of treatments can begin. There
> aren't any
> 	 > treatments quite ready for clinical trials yet, but
> several approaches
> 	 > that could be ready in the next few years. Once a
> treatment option is a
> 	 > possibility, everyone will want to try it, so it
> wouldn't be ethical to
> 	 > enroll them in a natural history study at that point.
> 	 >
> 	 > In short, a natural history study is important, and
> now is the
> 	 > time to conduct it.
> 	 >
> 	 > Right now we are in the middle of organizing the
> logistics of
> 	 > the study (how many centers and patients, length,
> things to measure,
> 	 > etc.). It looks like the study will have to be
> conducted in several
> 	 > senters, both in the U.S. and Europe.
> 	 >
> 	 > We need as many patients as possible with a confirmed
> diagnosis
> 	 > to be able to conduct this trial. So in part this post
> is an appeal to
> 	 > all of you to consider registering with the Jain
> Foundation if you
> 	 > haven't already, so that the Foundation can contact
> you regarding the
> 	 > natural history study when it happens, and help to
> establish the
> 	 > diagnosis if it hasn't yet been genetically confirmed.
> 	 >
> 	 > Best wishes,
> 	 > Brad
> 	 >
> 	 >
> 	 >
> 	 >
> 	 >
> 	 >
> 	 >
> 	 >
> 	 >
> 	 > _______________________
> 	 > Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ,
> New York NY, Newport Beach CA, Providence RI, Stamford CT, Washington
> DC, West Palm Beach FL, Wilmington DE, London UK, Hong Kong (associated
> office)
> 	 > CONFIDENTIALITY NOTICE
> 	 > This e-mail message from Edwards Angell Palmer & Dodge
> LLP and Edwards Angell Palmer & Dodge UK LLP is intended only for the
> individual or entity to which it is addressed. This e-mail may contain
> information that is privileged, confidential and exempt from disclosure
> under applicable law. If you are not the intended recipient, you are
> hereby notified that any dissemination, distribution or copying of this
> communication is strictly prohibited. If you received this e-mail by
> accident, please notify the sender immediately and destroy this e-mail
> and all copies of it. We take steps to protect against viruses but
> advise you to carry out your own checks and precautions as we accept no
> liability for any which remain. We may monitor emails sent to and from
> our server(s) to ensure regulatory compliance to protect our clients and
> business.
> 	 > Edwards Angell Palmer & Dodge UK LLP is a limited
> liability partnership registered in England (registered number OC333092)
> and is regulated by the Solicitors Regulation Authority. A list of
> members' names and their professional qualifications may be inspected at
> our registered office, One Fetter Lane, London EC4A 1JB, UK, telephone
> +44 207 583 4055.
> 	 > Disclosure Under U.S. IRS Circular 230: Edwards Angell
> Palmer & Dodge LLP informs you that any tax advice contained in this
> communication, including any attachments, was not intended or written to
> be used, and cannot be used, for the purpose of avoiding federal tax
> related penalties or promoting, marketing or recommending to another
> party any transaction or matter addressed herein.
> 	 >
>

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Monday, November 16, 2009 11:20 AM
To: dysferlin@yahoogroups.com
Subject: RE: [dysferlin] Re: Organizing a natural history study on dysferlin

 

I congratulate you and thank you for your efforts towards a treatment.
i dint realize that you were involved in to that extend in trying to help.
i think of lawyers as overpaid pencil pushers and ambulant chasers. (just kidding)

i gave one muscle biopsy and that's it. i like to preserve what ever i have left.
i still walk on my 49th year, but with extra help from healthy diet lots of sun (when available) some creatine, co q10, curcumin etc
 

any published papers from the study?


George Carpati unfortunately died a think last year. he was a genius in his field.
hope somebody can follow up on where he left.
thanks
mathew

---

To: dysferlin@yahoogroups.com
From: jthayer@eapdlaw.com
Date: Mon, 16 Nov 2009 10:31:48 -0500
Subject: RE: [dysferlin] Re: Organizing a natural history study on dysferlin

 

Matt,

 

As I understand it, there may still be a potential for Myoblasts.  I know that at least one doctor up in Quebec designed studies back in the 1990s that seemed to fail, but he still believes in the approach and thinks the studies were misinterpreted, or not done correctly, or something.  I understand that Health Canada may be holding up further work in the area for now.  Note that any myoblast approach means living on an immune suppressant for the rest of your life.  More money to big pharma for that!  It would also mean ongoing IV administrations at best. 

 

With respect to stem cells, my family and friends and I sponsored a cord blood stem cell study in mice in 2000 - 2002 or so at M.G.H.  Unfortunately, the results were not very promising.  As I understand it, some full length dysferlin protein was expressed in the skeletal muscles of the mice after the cord blood stems cells were administered, but not a clinically significant amount.  The study went on for a few years after our funding commitment (on NIH and MDA funding I think) to try to improve the results, but was eventually abandoned.  At least for now.  These things tend to come and go as new things are discovered that may be relevant.

 

I do not know enough about the applicability of embryonic stem cells, but I am not opposed to their use if warranted by science.  I believe that Brad, who is far more knowledgeable than I am with respect to the biology behind all of this, posted about embryonic stems cells some time ago in response to one of your posts.

 

I did not intentionally omit any reference to myoblasts or stem cells (embryonic or adult) in my earlier post, and Brad has discussed them before.  In any event, yes, they are potential treatments and all the more reason to register with the Jain Foundation. 

 

You are a realist, fine.  So am I.  I was diagnosed 22 years ago.  I have participated in 2 clinical trials (gentamicin and Myo-29), I have given 5 open muscle biopsies, several needle biopsies and countless blood draws for scientific research.  I have no idea when or if the efforts I have made will bear fruit.  I choose to contribute time, money, blood and tissue samples even though I remain skeptical and frustrated a lot of the time.  I totally support efforts in other countries, and in particular India, and I know the Jain Foundation does too.  You seem to think the rest of us live in la la land, or at least that is a reasonable inference from some of your posts.  That characterization is incorrect.  You have dysferlinopathy I understand, and yet are still quite mobile?  Believe me, you will become no less of a realist as the years go by and you slowly lose that mobility.

 

So, Matt, have you registered as a patient with the Jain Foundation?  I cannot ask them, of course, and you can tell me to "piss off "if you want, but I registered immediately when I knew it was possible, and I hope you and all others with the condition who read this will too.

 

Josh

 

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Monday, November 16, 2009 8:30 AM
To: dysferlin@yahoogroups.com
Subject: RE: [dysferlin] Re: Organizing a natural history study on dysferlin

 

by any means, i don't want to discourage people to come forward and participate to any approach that facilitates a potential therapy or treatment.
my frustration with the attitude of the big pharma comes out sometimes in light of events like the swine flue.
if there is no profit on the bottom line, there would be no participation of the ones that they own the
medical centers, universities, governments etc.
and if somebody comes up with a good idea for a potential treatment, eventually will find a wall of impedance from these.
we just have to settle for crams. I am not living in lala land, i am a realist.
look at acceleron.  (ace 31 etc) i am pretty sure that compound would potentially help lots of us.
but they waiting until they have something that could be marketed to the main stream. (i can read the head lines. "a cure for fat peopple" accelerons IPO at 50$ a share)...

you guys dint mention Myoblasts, or stem cells...whats up with that?
if i remember somebody here had an experience with myoblasts.
the cost i think is prohibitive.

i put my bets on India. if something comes will come from there.
lots more lgmd patients and doctors that have some altruism in them.
they just need some help from big pharma...
  Mathew
 

---

To: dysferlin@yahoogroups.com
From: bwilliams163@verizon.net
Date: Mon, 16 Nov 2009 05:04:49 +0000
Subject: [dysferlin] Re: Organizing a natural history study on dysferlin

 

Josh is very knowledgable about the economics and approval process. I'll just add a little bit to his post.

Besides "dysferlin-specific custom therapies" a brand new drug specifically designed to treat dysferlin deficiency, there are three general categories of drugs where the economics are more favorable.

1) drugs that are designed to treat a specific type of mutation--in theory they should work for a mutation in any gene, although there's the question of how much protein would be needed for a therapeutic effect, and there may be side effects that are gene specific. PTC-124 is in this category.

2) drugs that promote muscle growth, that may be beneficial for any type of muscular dystrophy. Drugs that inhibit myostatin (one was tested by Wyeth a while back) and therefore promote muscle growth are in this category.

3) drugs that are already approved for some completely different use having nothing to do with muscular dystrophy. Before PTC-124 was developed, another compound, gentomycin, which is approved as an antibiotic, was found to have some effect (less than PTC-124) in the same way. These already approved drugs will have to be tested in animals first, and will need a fairly large-scale screening to try to find one that works. In this case, there's not a safety issue (the drug is already approved) but one would have to show that it works.

--- In dysferlin@yahoogroups.com, "Thayer, Joshua" <jthayer@...> wrote:
>
> Matthew,
>
> You are correct that a compound that only targets the dysferlin protein
> probably will not be of interest to big pharma. It is possible that it
> would, because if the pharma company gets orphan drug status from the
> FDA for the compound, it can charge a lot of money per patient and
> obtain reimbursement. That possibility will be increased, of course, if
> there is proof of at least some critical mass of dysferlin deficient
> patients. But let's assume that that won't happen.
>
> Even so, the "by products" you describe could be extremely important,
> and our access to them could be facilitated by this proposed study. For
> example, Ataluren (PTC 124) is currently in Duschenne Dystrophy, Cystic
> Fibrosis and Hemophilia trials. Assuming Ataluren does not fail (which
> it might), it is of course possible that it will be approved in one or
> all of those other conditions, and quickly enough to be available off
> label for those of us with a nonsense mutation. But it is also possible
> that the FDA will want to see it tested in Dysferlinopathy and other
> conditions linked to such mutations. And, unless approved for
> dysferlinopathy, it might not be covered by insurance for us.
>
> Also, imagine an approach that generally repairs damaged muscle fiber
> notwithstanding the missing protein (or other factor) that requires
> faster and more thorough repair to avoid cell death. If this Natural
> History Study can be done, then at least we with Miyoshi Myopathy and
> LGMDIIB will have a shot at being included in a trial, which might
> provide some therapeutic value prior to approval.
>
> I understand your frustration with big pharma, and although you have
> blasted me before on an earlier exchange, you will have to trust me that
> I share your frustration. But I do hope that you are not trying to
> discourage people from participating in this important study to make a
> political point, and I hope you will participate as well.
>
> Josh
>
>
> ________________________________
>
> From: dysferlin@yahoogroups.com
> [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
> Sent: Sunday, November 15, 2009 11:01 PM
> To: dysferlin@yahoogroups.com
> Subject: RE: [dysferlin] Organizing a natural history study on
> dysferlin
>
>
>
>
> I am wondering if any pharmaceutical company would be interest
> in to any trial that involves couple hundred people where the potential
> of profits are virtually none.
> If we get any treatments IMHO would be as a "byproduct" of
> treatments of other disorders more "main stream".
> the doctors and the big pharma are more interest to lining their
> pockets than anything.
> (look at the h1n1 example...)
> Hope i am wrong.
> Mathew
>
> ________________________________
>
> To: dysferlin@yahoogroups.com
> From: bwilliams163@...
> Date: Mon, 16 Nov 2009 03:41:55 +0000
> Subject: [dysferlin] Organizing a natural history study on
> dysferlin
>
>
> At the Jain Foundation conference this past summer, one of the
> topics discussed at a satellite meeting was how to organize and conduct
> a natural history study on dysferlin deficiency.
>
> I've posted a synopsis of the conference in the files section of
> the groups page. The first page summarizes the natural history sattelite
> meeting.
>
> Why do a natural history study? There are a few reasons. One is
> to provide the infrastructure for future clinical trials. In order to
> conduct a clinical trial of some proposed treatment, one needs some
> simple measurement which will be able to tell if the treatment is
> effective. Knowing the typical rate of progression of dysferlin
> deficiency in the absence of treatment, or details about diagnostic
> tests such as MRIs, will be needed before a clinical trial can be
> started.
>
> Another is simply to have enough patients identified, and enough
> clinical centers involved in dysferlin research, that it is possible to
> conduct a clinical trial. If there aren't enough patients (a minimum
> will probably be at least 100), you can't do a clinical trial no matter
> how good an idea you have for a treatment.
>
> It's generally acknowledged that a natural history study will
> have to be done before a clinical trial will be possible. So even though
> a natural history study won't directly benefit patients, it has to
> happen before trials of treatments can begin. There aren't any
> treatments quite ready for clinical trials yet, but several approaches
> that could be ready in the next few years. Once a treatment option is a
> possibility, everyone will want to try it, so it wouldn't be ethical to
> enroll them in a natural history study at that point.
>
> In short, a natural history study is important, and now is the
> time to conduct it.
>
> Right now we are in the middle of organizing the logistics of
> the study (how many centers and patients, length, things to measure,
> etc.). It looks like the study will have to be conducted in several
> senters, both in the U.S. and Europe.
>
> We need as many patients as possible with a confirmed diagnosis
> to be able to conduct this trial. So in part this post is an appeal to
> all of you to consider registering with the Jain Foundation if you
> haven't already, so that the Foundation can contact you regarding the
> natural history study when it happens, and help to establish the
> diagnosis if it hasn't yet been genetically confirmed.
>
> Best wishes,
> Brad
>
>
>
>
>
>
>
>
>
> _______________________
> Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ, New York NY, Newport Beach CA, Providence RI, Stamford CT, Washington DC, West Palm Beach FL, Wilmington DE, London UK, Hong Kong (associated office)
> CONFIDENTIALITY NOTICE
> This e-mail message from Edwards Angell Palmer & Dodge LLP and Edwards Angell Palmer & Dodge UK LLP is intended only for the individual or entity to which it is addressed. This e-mail may contain information that is privileged, confidential and exempt from disclosure under applicable law. If you are not the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you received this e-mail by accident, please notify the sender immediately and destroy this e-mail and all copies of it. We take steps to protect against viruses but advise you to carry out your own checks and precautions as we accept no liability for any which remain. We may monitor emails sent to and from our server(s) to ensure regulatory compliance to protect our clients and business.
> Edwards Angell Palmer & Dodge UK LLP is a limited liability partnership registered in England (registered number OC333092) and is regulated by the Solicitors Regulation Authority. A list of members' names and their professional qualifications may be inspected at our registered office, One Fetter Lane, London EC4A 1JB, UK, telephone +44 207 583 4055.
> Disclosure Under U.S. IRS Circular 230: Edwards Angell Palmer & Dodge LLP informs you that any tax advice contained in this communication, including any attachments, was not intended or written to be used, and cannot be used, for the purpose of avoiding federal tax related penalties or promoting, marketing or recommending to another party any transaction or matter addressed herein.
>

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Monday, November 16, 2009 8:30 AM
To: dysferlin@yahoogroups.com
Subject: RE: [dysferlin] Re: Organizing a natural history study on dysferlin

 

by any means, i don't want to discourage people to come forward and participate to any approach that facilitates a potential therapy or treatment.
my frustration with the attitude of the big pharma comes out sometimes in light of events like the swine flue.
if there is no profit on the bottom line, there would be no participation of the ones that they own the
medical centers, universities, governments etc.
and if somebody comes up with a good idea for a potential treatment, eventually will find a wall of impedance from these.
we just have to settle for crams. I am not living in lala land, i am a realist.
look at acceleron.  (ace 31 etc) i am pretty sure that compound would potentially help lots of us.
but they waiting until they have something that could be marketed to the main stream. (i can read the head lines. "a cure for fat peopple" accelerons IPO at 50$ a share)...

you guys dint mention Myoblasts, or stem cells...whats up with that?
if i remember somebody here had an experience with myoblasts.
the cost i think is prohibitive.

i put my bets on India. if something comes will come from there.
lots more lgmd patients and doctors that have some altruism in them.
they just need some help from big pharma...
  Mathew
 

---

To: dysferlin@yahoogroups.com
From: bwilliams163@verizon.net
Date: Mon, 16 Nov 2009 05:04:49 +0000
Subject: [dysferlin] Re: Organizing a natural history study on dysferlin

 

Josh is very knowledgable about the economics and approval process. I'll just add a little bit to his post.

Besides "dysferlin-specific custom therapies" a brand new drug specifically designed to treat dysferlin deficiency, there are three general categories of drugs where the economics are more favorable.

1) drugs that are designed to treat a specific type of mutation--in theory they should work for a mutation in any gene, although there's the question of how much protein would be needed for a therapeutic effect, and there may be side effects that are gene specific. PTC-124 is in this category.

2) drugs that promote muscle growth, that may be beneficial for any type of muscular dystrophy. Drugs that inhibit myostatin (one was tested by Wyeth a while back) and therefore promote muscle growth are in this category.

3) drugs that are already approved for some completely different use having nothing to do with muscular dystrophy. Before PTC-124 was developed, another compound, gentomycin, which is approved as an antibiotic, was found to have some effect (less than PTC-124) in the same way. These already approved drugs will have to be tested in animals first, and will need a fairly large-scale screening to try to find one that works. In this case, there's not a safety issue (the drug is already approved) but one would have to show that it works.

--- In dysferlin@yahoogroups.com, "Thayer, Joshua" <jthayer@...> wrote:
>
> Matthew,
>
> You are correct that a compound that only targets the dysferlin protein
> probably will not be of interest to big pharma. It is possible that it
> would, because if the pharma company gets orphan drug status from the
> FDA for the compound, it can charge a lot of money per patient and
> obtain reimbursement. That possibility will be increased, of course, if
> there is proof of at least some critical mass of dysferlin deficient
> patients. But let's assume that that won't happen.
>
> Even so, the "by products" you describe could be extremely important,
> and our access to them could be facilitated by this proposed study. For
> example, Ataluren (PTC 124) is currently in Duschenne Dystrophy, Cystic
> Fibrosis and Hemophilia trials. Assuming Ataluren does not fail (which
> it might), it is of course possible that it will be approved in one or
> all of those other conditions, and quickly enough to be available off
> label for those of us with a nonsense mutation. But it is also possible
> that the FDA will want to see it tested in Dysferlinopathy and other
> conditions linked to such mutations. And, unless approved for
> dysferlinopathy, it might not be covered by insurance for us.
>
> Also, imagine an approach that generally repairs damaged muscle fiber
> notwithstanding the missing protein (or other factor) that requires
> faster and more thorough repair to avoid cell death. If this Natural
> History Study can be done, then at least we with Miyoshi Myopathy and
> LGMDIIB will have a shot at being included in a trial, which might
> provide some therapeutic value prior to approval.
>
> I understand your frustration with big pharma, and although you have
> blasted me before on an earlier exchange, you will have to trust me that
> I share your frustration. But I do hope that you are not trying to
> discourage people from participating in this important study to make a
> political point, and I hope you will participate as well.
>
> Josh
>
>
> ________________________________
>
> From: dysferlin@yahoogroups.com
> [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
> Sent: Sunday, November 15, 2009 11:01 PM
> To: dysferlin@yahoogroups.com
> Subject: RE: [dysferlin] Organizing a natural history study on
> dysferlin
>
>
>
>
> I am wondering if any pharmaceutical company would be interest
> in to any trial that involves couple hundred people where the potential
> of profits are virtually none.
> If we get any treatments IMHO would be as a "byproduct" of
> treatments of other disorders more "main stream".
> the doctors and the big pharma are more interest to lining their
> pockets than anything.
> (look at the h1n1 example...)
> Hope i am wrong.
> Mathew
>
> ________________________________
>
> To: dysferlin@yahoogroups.com
> From: bwilliams163@...
> Date: Mon, 16 Nov 2009 03:41:55 +0000
> Subject: [dysferlin] Organizing a natural history study on
> dysferlin
>
>
> At the Jain Foundation conference this past summer, one of the
> topics discussed at a satellite meeting was how to organize and conduct
> a natural history study on dysferlin deficiency.
>
> I've posted a synopsis of the conference in the files section of
> the groups page. The first page summarizes the natural history sattelite
> meeting.
>
> Why do a natural history study? There are a few reasons. One is
> to provide the infrastructure for future clinical trials. In order to
> conduct a clinical trial of some proposed treatment, one needs some
> simple measurement which will be able to tell if the treatment is
> effective. Knowing the typical rate of progression of dysferlin
> deficiency in the absence of treatment, or details about diagnostic
> tests such as MRIs, will be needed before a clinical trial can be
> started.
>
> Another is simply to have enough patients identified, and enough
> clinical centers involved in dysferlin research, that it is possible to
> conduct a clinical trial. If there aren't enough patients (a minimum
> will probably be at least 100), you can't do a clinical trial no matter
> how good an idea you have for a treatment.
>
> It's generally acknowledged that a natural history study will
> have to be done before a clinical trial will be possible. So even though
> a natural history study won't directly benefit patients, it has to
> happen before trials of treatments can begin. There aren't any
> treatments quite ready for clinical trials yet, but several approaches
> that could be ready in the next few years. Once a treatment option is a
> possibility, everyone will want to try it, so it wouldn't be ethical to
> enroll them in a natural history study at that point.
>
> In short, a natural history study is important, and now is the
> time to conduct it.
>
> Right now we are in the middle of organizing the logistics of
> the study (how many centers and patients, length, things to measure,
> etc.). It looks like the study will have to be conducted in several
> senters, both in the U.S. and Europe.
>
> We need as many patients as possible with a confirmed diagnosis
> to be able to conduct this trial. So in part this post is an appeal to
> all of you to consider registering with the Jain Foundation if you
> haven't already, so that the Foundation can contact you regarding the
> natural history study when it happens, and help to establish the
> diagnosis if it hasn't yet been genetically confirmed.
>
> Best wishes,
> Brad
>
>
>
>
>
>
>
>
>
> _______________________
> Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ, New York NY, Newport Beach CA, Providence RI, Stamford CT, Washington DC, West Palm Beach FL, Wilmington DE, London UK, Hong Kong (associated office)
> CONFIDENTIALITY NOTICE
> This e-mail message from Edwards Angell Palmer & Dodge LLP and Edwards Angell Palmer & Dodge UK LLP is intended only for the individual or entity to which it is addressed. This e-mail may contain information that is privileged, confidential and exempt from disclosure under applicable law. If you are not the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you received this e-mail by accident, please notify the sender immediately and destroy this e-mail and all copies of it. We take steps to protect against viruses but advise you to carry out your own checks and precautions as we accept no liability for any which remain. We may monitor emails sent to and from our server(s) to ensure regulatory compliance to protect our clients and business.
> Edwards Angell Palmer & Dodge UK LLP is a limited liability partnership registered in England (registered number OC333092) and is regulated by the Solicitors Regulation Authority. A list of members' names and their professional qualifications may be inspected at our registered office, One Fetter Lane, London EC4A 1JB, UK, telephone +44 207 583 4055.
> Disclosure Under U.S. IRS Circular 230: Edwards Angell Palmer & Dodge LLP informs you that any tax advice contained in this communication, including any attachments, was not intended or written to be used, and cannot be used, for the purpose of avoiding federal tax related penalties or promoting, marketing or recommending to another party any transaction or matter addressed herein.
>

Josh is very knowledgable about the economics and approval process.  I'll just
add a little bit to his post.

Besides "dysferlin-specific custom therapies" a brand new drug specifically
designed to treat dysferlin deficiency, there are three general categories of
drugs where the economics are more favorable.

1) drugs that are designed to treat a specific type of mutation--in theory they
should work for a mutation in any gene, although there's the question of how
much protein would be needed for a therapeutic effect, and there may be side
effects that are gene specific.  PTC-124 is in this category.

2) drugs that promote muscle growth, that may be beneficial for any type of
muscular dystrophy.  Drugs that inhibit myostatin (one was tested by Wyeth a
while back) and therefore promote muscle growth are in this category.

3) drugs that are already approved for some completely different use having
nothing to do with muscular dystrophy.  Before PTC-124 was developed, another
compound, gentomycin, which is approved as an antibiotic, was found to have some
effect (less than PTC-124) in the same way.   These already approved drugs will
have to be tested in animals first, and will need a fairly large-scale screening
to try to find one that works.  In this case, there's not a safety issue (the
drug is already approved) but one would have to show that it works.

--- In dysferlin@yahoogroups.com, "Thayer, Joshua" <jthayer@...> wrote:
>
> Matthew,
>
> You are correct that a compound that only targets the dysferlin protein
> probably will not be of interest to big pharma.  It is possible that it
> would, because if the pharma company gets orphan drug status from the
> FDA for the compound, it can charge a lot of money per patient and
> obtain reimbursement.  That possibility will be increased, of course, if
> there is proof of at least some critical mass of dysferlin deficient
> patients.  But let's assume that that won't happen.
>
> Even so, the "by products" you describe could be extremely important,
> and our access to them could be facilitated by this proposed study.  For
> example, Ataluren (PTC 124) is currently in Duschenne Dystrophy, Cystic
> Fibrosis and Hemophilia trials.  Assuming Ataluren does not fail (which
> it might), it is of course possible that it will be approved in one or
> all of those other conditions, and quickly enough to be available off
> label for those of us with a nonsense mutation.  But it is also possible
> that the FDA will want to see it tested in Dysferlinopathy and other
> conditions linked to such mutations.  And, unless approved for
> dysferlinopathy, it might not be covered by insurance for us.
>
> Also, imagine an approach that generally repairs damaged muscle fiber
> notwithstanding the missing protein (or other factor) that requires
> faster and more thorough repair to avoid cell death.  If this Natural
> History Study can be done, then at least we with Miyoshi Myopathy and
> LGMDIIB will have a shot at being included in a trial, which might
> provide some therapeutic value prior to approval.
>
> I understand your frustration with big pharma, and although you have
> blasted me before on an earlier exchange, you will have to trust me that
> I share your frustration.  But I do hope that you are not trying to
> discourage people from participating in this important study to make a
> political point, and I hope you will participate as well.
>
> Josh
>
>
> ________________________________
>
>  From: dysferlin@yahoogroups.com
> [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
>  Sent: Sunday, November 15, 2009 11:01 PM
>  To: dysferlin@yahoogroups.com
>  Subject: RE: [dysferlin] Organizing a natural history study on
> dysferlin
>
>
>
>
>  I am wondering if any pharmaceutical company would be interest
> in to any trial that involves couple hundred people where the potential
> of profits are virtually none.
>  If we get any treatments IMHO would be as a "byproduct" of
> treatments of other disorders more "main stream".
>  the doctors and the big pharma are more interest to lining their
> pockets than anything.
>  (look at the h1n1 example...)
>  Hope  i am wrong.
>  Mathew
>
> ________________________________
>
>  To: dysferlin@yahoogroups.com
>  From: bwilliams163@...
>  Date: Mon, 16 Nov 2009 03:41:55 +0000
>  Subject: [dysferlin] Organizing a natural history study on
> dysferlin
>
>
>  At the Jain Foundation conference this past summer, one of the
> topics discussed at a satellite meeting was how to organize and conduct
> a natural history study on dysferlin deficiency.
>
>  I've posted a synopsis of the conference in the files section of
> the groups page. The first page summarizes the natural history sattelite
> meeting.
>
>  Why do a natural history study? There are a few reasons. One is
> to provide the infrastructure for future clinical trials. In order to
> conduct a clinical trial of some proposed treatment, one needs some
> simple measurement which will be able to tell if the treatment is
> effective. Knowing the typical rate of progression of dysferlin
> deficiency in the absence of treatment, or details about diagnostic
> tests such as MRIs, will be needed before a clinical trial can be
> started.
>
>  Another is simply to have enough patients identified, and enough
> clinical centers involved in dysferlin research, that it is possible to
> conduct a clinical trial. If there aren't enough patients (a minimum
> will probably be at least 100), you can't do a clinical trial no matter
> how good an idea you have for a treatment.
>
>  It's generally acknowledged that a natural history study will
> have to be done before a clinical trial will be possible. So even though
> a natural history study won't directly benefit patients, it has to
> happen before trials of treatments can begin. There aren't any
> treatments quite ready for clinical trials yet, but several approaches
> that could be ready in the next few years. Once a treatment option is a
> possibility, everyone will want to try it, so it wouldn't be ethical to
> enroll them in a natural history study at that point.
>
>  In short, a natural history study is important, and now is the
> time to conduct it.
>
>  Right now we are in the middle of organizing the logistics of
> the study (how many centers and patients, length, things to measure,
> etc.). It looks like the study will have to be conducted in several
> senters, both in the U.S. and Europe.
>
>  We need as many patients as possible with a confirmed diagnosis
> to be able to conduct this trial. So in part this post is an appeal to
> all of you to consider registering with the Jain Foundation if you
> haven't already, so that the Foundation can contact you regarding the
> natural history study when it happens, and help to establish the
> diagnosis if it hasn't yet been genetically confirmed.
>
>  Best wishes,
>  Brad
>
>
>
>
>
>
>
>
>
> _______________________
> Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ, New York NY, Newport
Beach CA, Providence RI, Stamford CT, Washington DC, West Palm Beach FL,
Wilmington DE, London UK, Hong Kong (associated office)
> CONFIDENTIALITY NOTICE
> This e-mail message from Edwards Angell Palmer & Dodge LLP and Edwards Angell
Palmer & Dodge UK LLP is intended only for the individual or entity to which it
is addressed. This e-mail may contain information that is privileged,
confidential and exempt from disclosure under applicable law. If you are not the
intended recipient, you are hereby notified that any dissemination, distribution
or copying of this communication is strictly prohibited. If you received this
e-mail by accident, please notify the sender immediately and destroy this e-mail
and all copies of it. We take steps to protect against viruses but advise you to
carry out your own checks and precautions as we accept no liability for any
which remain. We may monitor emails sent to and from our server(s) to ensure
regulatory compliance to protect our clients and business.
> Edwards Angell Palmer & Dodge UK LLP is a limited liability partnership
registered in England (registered number OC333092) and is regulated by the
Solicitors Regulation Authority. A list of members' names and their professional
qualifications may be inspected at our registered office, One Fetter Lane,
London EC4A 1JB, UK, telephone +44 207 583 4055.
> Disclosure Under U.S. IRS Circular 230: Edwards Angell Palmer & Dodge LLP
informs you that any tax advice contained in this communication, including any
attachments, was not intended or written to be used, and cannot be used, for the
purpose of avoiding federal tax related penalties or promoting, marketing or
recommending to another party any transaction or matter addressed herein.
>

---

From: dysferlin@yahoogroups.com [mailto:dysferlin@yahoogroups.com] On Behalf Of MATHEW anas
Sent: Sunday, November 15, 2009 11:01 PM
To: dysferlin@yahoogroups.com
Subject: RE: [dysferlin] Organizing a natural history study on dysferlin

 

I am wondering if any pharmaceutical company would be interest in to any trial that involves couple hundred people where the potential of profits are virtually none.
If we get any treatments IMHO would be as a "byproduct" of treatments of other disorders more "main stream".
the doctors and the big pharma are more interest to lining their pockets than anything.
(look at the h1n1 example...)
Hope  i am wrong.
Mathew

---

To: dysferlin@yahoogroups.com
From: bwilliams163@verizon.net
Date: Mon, 16 Nov 2009 03:41:55 +0000
Subject: [dysferlin] Organizing a natural history study on dysferlin

 

At the Jain Foundation conference this past summer, one of the topics discussed at a satellite meeting was how to organize and conduct a natural history study on dysferlin deficiency.

I've posted a synopsis of the conference in the files section of the groups page. The first page summarizes the natural history sattelite meeting.

Why do a natural history study? There are a few reasons. One is to provide the infrastructure for future clinical trials. In order to conduct a clinical trial of some proposed treatment, one needs some simple measurement which will be able to tell if the treatment is effective. Knowing the typical rate of progression of dysferlin deficiency in the absence of treatment, or details about diagnostic tests such as MRIs, will be needed before a clinical trial can be started.

Another is simply to have enough patients identified, and enough clinical centers involved in dysferlin research, that it is possible to conduct a clinical trial. If there aren't enough patients (a minimum will probably be at least 100), you can't do a clinical trial no matter how good an idea you have for a treatment.

It's generally acknowledged that a natural history study will have to be done before a clinical trial will be possible. So even though a natural history study won't directly benefit patients, it has to happen before trials of treatments can begin. There aren't any treatments quite ready for clinical trials yet, but several approaches that could be ready in the next few years. Once a treatment option is a possibility, everyone will want to try it, so it wouldn't be ethical to enroll them in a natural history study at that point.

In short, a natural history study is important, and now is the time to conduct it.

Right now we are in the middle of organizing the logistics of the study (how many centers and patients, length, things to measure, etc.). It looks like the study will have to be conducted in several senters, both in the U.S. and Europe.

We need as many patients as possible with a confirmed diagnosis to be able to conduct this trial. So in part this post is an appeal to all of you to consider registering with the Jain Foundation if you haven't already, so that the Foundation can contact you regarding the natural history study when it happens, and help to establish the diagnosis if it hasn't yet been genetically confirmed.

Best wishes,
Brad

_______________________
Boston MA, Ft. Lauderdale FL, Hartford CT, Madison NJ, New York NY, Newport Beach CA, Providence RI, Stamford CT, Washington DC, West Palm Beach FL, Wilmington DE, London UK, Hong Kong (associated office)

CONFIDENTIALITY NOTICE
This e-mail message from Edwards Angell Palmer & Dodge LLP and Edwards Angell Palmer & Dodge UK LLP is intended only for the individual or entity to which it is addressed. This e-mail may contain information that is privileged, confidential and exempt from disclosure under applicable law. If you are not the intended recipient, you are hereby notified that any dissemination, distribution or copying of this communication is strictly prohibited. If you received this e-mail by accident, please notify the sender immediately and destroy this e-mail and all copies of it. We take steps to protect against viruses but advise you to carry out your own checks and precautions as we accept no liability for any which remain. We may monitor emails sent to and from our server(s) to ensure regulatory compliance to protect our clients and business.

Edwards Angell Palmer & Dodge UK LLP is a limited liability partnership registered in England (registered number OC333092) and is regulated by the Solicitors Regulation Authority. A list of members' names and their professional qualifications may be inspected at our registered office, One Fetter Lane, London EC4A 1JB, UK, telephone +44 207 583 4055.

Disclosure Under U.S. IRS Circular 230: Edwards Angell Palmer & Dodge LLP informs you that any tax advice contained in this communication, including any attachments, was not intended or written to be used, and cannot be used, for the purpose of avoiding federal tax related penalties or promoting, marketing or recommending to another party any transaction or matter addressed herein.

 

At the Jain Foundation conference this past summer, one of the topics discussed
at a satellite meeting was how to organize and conduct a natural history study
on dysferlin deficiency.

I've posted a synopsis of the conference in the files section of the groups
page.  The first page summarizes the natural history sattelite meeting.

Why do a natural history study?  There are a few reasons.  One is to provide the
infrastructure for future clinical trials.  In order to conduct a clinical trial
of some proposed treatment, one needs some simple measurement which will be able
to tell if the treatment is effective.  Knowing the typical rate of progression
of dysferlin deficiency in the absence of treatment, or details about diagnostic
tests such as MRIs, will be needed before a clinical trial can be started.

Another is simply to have enough patients identified, and enough clinical
centers involved in dysferlin research, that it is possible to conduct a
clinical trial.  If there aren't enough patients (a minimum will probably be at
least 100), you can't do a clinical trial no matter how good an idea you have
for a treatment.

It's generally acknowledged that a natural history study will have to be done
before a clinical trial will be possible.  So even though a natural history
study won't directly benefit patients, it has to happen before trials of
treatments can begin.  There aren't any treatments quite ready for clinical
trials yet, but several approaches that could be ready in the next few years. 
Once a treatment option is a possibility, everyone will want to try it, so it
wouldn't be ethical to enroll them in a natural history study at that point.

In short, a natural history study is important, and now is the time to conduct
it.

Right now we are in the middle of organizing the logistics of the study (how
many centers and patients, length, things to measure, etc.).  It looks like the
study will have to be conducted in several senters, both in the U.S. and Europe.

We need as many patients as possible with a confirmed diagnosis to be able to
conduct this trial.  So in part this post is an appeal to all of you to consider
registering with the Jain Foundation if you haven't already, so that the
Foundation can contact you regarding the natural history study when it happens,
and help to establish the diagnosis if it hasn't yet been genetically confirmed.

Best wishes,
Brad

Hi Elaine (and everyone),

A little bit about FKRP.  FKRP is the gene responsible for LGMD Type 2I.  In
parts of Northern and Western Europe it's one of the most common types of LGMD
(there's one particular mutation that's quite common) but it's rare in other
parts of the world.  So, often people are screened for FKRP mutations because
its easier to look for than dysferlin mutations (with FKRP it's one particular
mutation and it's a small gene, and pretty common, dysferlin is a very large
gene with lots of different mutations).  The laboratory probably wanted to rule
out an FKRP mutation first before looking for dysferlin mutations.

As Louise says, most often FKRP mutations cause congenital muscular dystrophy,
but sometimes it can have adult onset and look clinically like dysferlin
deficiency.

If dysferlin deficiency is the diagnosis, then as Louise says it could only be
passed to children if the other parent also has a mutation.

I work part time at the Jain Foundation.  We have a patient registry, and we do
know of another patient in Ireland with dysferlin deficiency.  It always kind of
brings mixed feelings to hear about other patients, on one hand it's always sad
that someone else has to deal with this, but it made me feel much less alone
when I first made contact with other patients.

Thanks for writing.  Hope this information is helpful, and best wishes.

Brad

--- In dysferlin@yahoogroups.com, Louise Needham <louiseneedham@...> wrote:
>
>
> Hi Elaine,
>
>
>
> My name is Louise and I actually live in Newcastle.  My mum and aunt both have
limb-girdle muscular dystrophy, but do not have the dysferlin mutation so the
cause is a mystery.  Me and my sister are unaffected (but must be carriers),
since most types of muscular dystrophy are recessive.  So it's unlikely your
children would be affected unless your husband is also a carrier.  If you're
worried you should see a genetic counsellor because they can assess the risks
and explain everything to you.
>
> I have studied genetics at the centre for life in newcastle (where the testing
is done), and can tell you that being negative for the FKRP mutation is a good
thing.  This gene mutation causes congenital muscular dystrophy (from birth), so
i guess they were just checking that's not what you have.
>
> There are so many different types of LGMD that most of them haven't been
classified, but the onset seems really variable.  My mum first showed signs
during her first pregnancy aged 29, and has gradually gotten worse over time. 
However, now aged 53 she still manages to walk short distances and only uses the
wheelchair for more strenuous things like shopping.  Swimming seems to be a good
form of exercise for her and doesn't put too much strain on her muscles.
>
>
>
> Hope that helps a bit,
>
>
>
> Louise
>
>
>
> To: dysferlin@yahoogroups.com
> From: ebd197@...
> Date: Fri, 13 Nov 2009 01:44:51 -0800
> Subject: Re: [dysferlin] Re: A reintroduction and a question...
>
>
>
>
>
>
>
> Hi Folks,
>
> My name is Elaine and I'm 35 years old from Ireland.  I wrote on this website
months ago and it totally knocked me for six the stories i was reading about
people.  I am currently awaiting genetic testing results from Newcastle,
England.  Tests so far have shown the Dysferlin but i am waiting for a 100%
diagnosis.  I come from a family of 4.  I have 2 brothers and one sister and all
them are fit as fiddles.  I myself was a very fit, active girl until I first
noticed muscle weakness in the legs at the age of 24 and have slowly been
getting worse.  It has now spead to my arms and back.  My Neurologist in Dublin
has told me that there is no-one else in Ireland that he knows of with this
dysferlinopathy.  So i'm a guenipig for them now.  One part of the Genetic
Testing came back saying that the FKRP Gene Mutation was negative.  Can anyone
tell me what this means, is it a good thing or a bad thing???.  I don't want to
look up anything because it only gets me down what i have been reading. My
Neurologist wants me to wait until all genetic testing is done and then he will
meet with myself and my hubby.
> I am working fulltime at the moment in a clinic for disabled children.  I
notice alot of peple cannot go up on tip toe.  I can for now.  This disease
really gets to me at times and my biggest fear is ending up in a wheelchair. 
That's what knocked me for six when i started reading people's stories.  i had
to turn off the computer for weeks.
> Myself and my hubby currently have no kids and am terrified to have one in
case they end up like me.  Can anyone ease my mind about this.
> I think you are all so brave with coping with this terrible illness, i have
good days and bad days but the fear is of getting worse......
>
> take care for now.
> Elaine.
>
>
>
>
>
> From: baw1064 <bwilliams163@...>
> To: dysferlin@yahoogroups.com
> Sent: Thu, November 12, 2009 6:51:23 PM
> Subject: [dysferlin] Re: A reintroduction and a question...
>
>
>
> Hi Bryan,
>
> Just a quick comment on your diagnosis. It is possible for Miyoshi to be
caused by mutations in other genes besides dysferlin, there are at least two
other genes that have been reported in the literature (one identified, the other
not yet identified, but its location in the genome is known pretty accurately).
It's also possible that dysferlin might show up on a blood tests (a mutation
doesn't necessarily mean a person won't have any of the protein) but isn't able
to function properly in muscle.
>
> Did your doctor have any thoughts on what the next step in a diagnosis should
be?
>
> Best wishes,
> Brad
>
> --- In dysferlin@yahoogrou ps.com, "b5sense" <b5sense@ > wrote:
> >
> > Hello everybody,
> > It's been a while since I posted anything so I figured I'd reintroduce
myself. I'm Bryan Nickell. I just turned thirty and was diagnosed with Miyoshi
Myopathy about six years ago. It is doing a pretty good number on my calf
muscles, my left being smaller than my right. I wear Blue Rocker Toe Off braces
which are pretty uncomfortable but give me enough support that I can be somewhat
active. I was an athlete my whole life so I'm having to get used to this new
body that I have. I just got married about two months ago and my wife and I own
our own business which is an old fashioned soda fountain and retail store in
North Carolina.
> >
> > I was writing because I had a question for people in the group. My doctor is
confident (with what they know now) with my Miyoshi diagnosis, but a blood test
that was done at the Mayo Clinic found that I do have the dysferlin protein. I
was wondering if this was true for anybody else in the group? My doctor said it
was rare to have Miyoshi that presented itself like this, but I was hoping maybe
somebody else out there has had the same experience as me. It can be pretty
lonely trying to cope with a disease like this that many people don't seem to
understand.
> >
> > Thanks for responding if you do, and if not I just want everyone to know
that it is a great comfort knowing y'all are out there. I am not happy that any
of us have these diseases, but I feel grateful that we all have each other. I
hope everyone is doing well and I look forward to hearing from you.
> >
> > Thanks again,
> > Bryan Nickell
> >
>
>
>
>
>
>
>
>
> _________________________________________________________________
> Learn how to add other email accounts to Hotmail in 3 easy steps.
> http://clk.atdmt.com/UKM/go/167688463/direct/01/
>

Hey Bryan,

My doctor at the Mayo Clinic was pretty confident that I had Miyoshi Myopathy
too.  I had the blood tests and muscle biopsy done and both show that I have the
dysferlin protein, the blood test showed elevated levels of CK, but not the
extreme levels many in this group have.  My symptoms presented with wasting of
my calf muscles and the inability to toe walk.  EMG testing showed other distal
muscles affected.  I was diagnosed last year, I will turn 40 next April.  It
appears that my brother who is one year older is going through the same thing. 
He hasn't gone to the doctor yet, but is planning too after the beginning of the
new year.  His progression seems to be much more dramatic than mine.  I have
four brothers and so fare just one and myself seem to have this.  My brother
started showing symptoms about the same time I did.  It will be interesting to
see if he has the dysferlin protien.

I'll quit rambling, but I just wanted you to know that you are not the only one
out there with the symptoms of Miyoshi Myopathy and has the dysferlin protien.

Donna Pond

--- In dysferlin@yahoogroups.com, "b5sense" <b5sense@...> wrote:
>
> Hello everybody,
> It's been a while since I posted anything so I figured I'd reintroduce myself.
I'm Bryan Nickell. I just turned thirty and was diagnosed with Miyoshi Myopathy
about six years ago. It is doing a pretty good number on my calf muscles, my
left being smaller than my right. I wear Blue Rocker Toe Off braces which are
pretty uncomfortable but give me enough support that I can be somewhat active. I
was an athlete my whole life so I'm having to get used to this new body that I
have. I just got married about two months ago and my wife and I own our own
business which is an old fashioned soda fountain and retail store in North
Carolina.
>
> I was writing because I had a question for people in the group. My doctor is
confident (with what they know now) with my Miyoshi diagnosis, but a blood test
that was done at the Mayo Clinic found that I do have the dysferlin protein. I
was wondering if this was true for anybody else in the group? My doctor said it
was rare to have Miyoshi that presented itself like this, but I was hoping maybe
somebody else out there has had the same experience as me. It can be pretty
lonely trying to cope with a disease like this that many people don't seem to
understand.
>
> Thanks for responding if you do, and if not I just want everyone to know that
it is a great comfort knowing y'all are out there. I am not happy that any of us
have these diseases, but I feel grateful that we all have each other. I hope
everyone is doing well and I look forward to hearing from you.
>
> Thanks again,
> Bryan Nickell
>

Hi Bryan,

Just a quick comment on your diagnosis.  It is possible for Miyoshi to be caused
by mutations in other genes besides dysferlin, there are at least two other
genes that have been reported in the literature (one identified, the other not
yet identified, but its location in the genome is known pretty accurately). 
It's also possible that dysferlin might show up on a blood tests (a mutation
doesn't necessarily mean a person won't have any of the protein) but isn't able
to function properly in muscle.

Did your doctor have any thoughts on what the next step in a diagnosis should
be?

Best wishes,
Brad

--- In dysferlin@yahoogroups.com, "b5sense" <b5sense@...> wrote:
>
> Hello everybody,
> It's been a while since I posted anything so I figured I'd reintroduce myself.
I'm Bryan Nickell. I just turned thirty and was diagnosed with Miyoshi Myopathy
about six years ago. It is doing a pretty good number on my calf muscles, my
left being smaller than my right. I wear Blue Rocker Toe Off braces which are
pretty uncomfortable but give me enough support that I can be somewhat active. I
was an athlete my whole life so I'm having to get used to this new body that I
have. I just got married about two months ago and my wife and I own our own
business which is an old fashioned soda fountain and retail store in North
Carolina.
>
> I was writing because I had a question for people in the group. My doctor is
confident (with what they know now) with my Miyoshi diagnosis, but a blood test
that was done at the Mayo Clinic found that I do have the dysferlin protein. I
was wondering if this was true for anybody else in the group? My doctor said it
was rare to have Miyoshi that presented itself like this, but I was hoping maybe
somebody else out there has had the same experience as me. It can be pretty
lonely trying to cope with a disease like this that many people don't seem to
understand.
>
> Thanks for responding if you do, and if not I just want everyone to know that
it is a great comfort knowing y'all are out there. I am not happy that any of us
have these diseases, but I feel grateful that we all have each other. I hope
everyone is doing well and I look forward to hearing from you.
>
> Thanks again,
> Bryan Nickell
>

Hello everybody,
It's been a while since I posted anything so I figured I'd reintroduce myself.
I'm Bryan Nickell. I just turned thirty and was diagnosed with Miyoshi Myopathy
about six years ago. It is doing a pretty good number on my calf muscles, my
left being smaller than my right. I wear Blue Rocker Toe Off braces which are
pretty uncomfortable but give me enough support that I can be somewhat active. I
was an athlete my whole life so I'm having to get used to this new body that I
have. I just got married about two months ago and my wife and I own our own
business which is an old fashioned soda fountain and retail store in North
Carolina.

I was writing because I had a question for people in the group. My doctor is
confident (with what they know now) with my Miyoshi diagnosis, but a blood test
that was done at the Mayo Clinic found that I do have the dysferlin protein. I
was wondering if this was true for anybody else in the group? My doctor said it
was rare to have Miyoshi that presented itself like this, but I was hoping maybe
somebody else out there has had the same experience as me. It can be pretty
lonely trying to cope with a disease like this that many people don't seem to
understand.

Thanks for responding if you do, and if not I just want everyone to know that it
is a great comfort knowing y'all are out there. I am not happy that any of us
have these diseases, but I feel grateful that we all have each other. I hope
everyone is doing well and I look forward to hearing from you.

Thanks again,
Bryan Nickell