http://www.eurekalert.org/pub_releases/2006-11/mgh-ndf112106.php

New data from NIH lab confirms protocol to reverse type 1 diabetes in mice

Data also support role for adult spleen cells in regeneration of beta cells

New data published in the Nov. 24 issue of Science provide further support for a protocol to reverse type 1 diabetes in mice and new evidence that adult precursor cells from the spleen can contribute to the regeneration of beta cells. In 2001 and 2003, researchers at Massachusetts General Hospital (MGH) demonstrated the efficacy of a protocol to reverse of type 1 diabetes in diabetic mice. Three studies from other institutions published in the March 24, 2006 issue of Science confirmed that the MGH-developed protocol can reverse the underlying disease but were inconclusive on the role of spleen cells in the recovery of insulin-producing pancreatic islets. The new data from a study performed at the National Institutes of Health (NIH), published as a technical comment, provides additional confirmation of the ability to reverse type 1 diabetes and on the role of the spleen cells in islet regeneration.

"This data from the NIH and the earlier studies have added significantly to the understanding of how diabetes may be reversed," says Denise Faustman, MD, PhD, director of the Immunobiology Laboratory at Massachusetts General Hospital, primary author of the 2001 and 2003 studies and co-corresponding author of the current report. "It is still early, but it appears that there are multiple potential sources for regenerating islets. As a research community we should pursue all avenues. We're excited to see what will happen in humans."

In the 2001 and 2003 studies, Faustman and colleagues treated end-stage nonobese diabetic (NOD) mice with Freund's complete adjuvant, a substance that suppresses the activity of the immune cells that destroy islets in type 1 diabetes. They also introduced donor spleen cells to retrain the immune system not to attack islets and found that the protocol not only halted the immune destruction caused by diabetes but also allowed the insulin-producing pancreatic islet cells to regenerate. Evidence indicated that the spleen cells were the source of at least some of the regenerated islet cell and hastened the restoration of blood sugar levels.

The direct contribution of spleen cells to islet recovery, first described in the 2003 study, is confirmed in the current work. NIH researchers used cell lineage tracking in the form of Y-chromosomal fluorescence in situ hybridization (FISH), in combination with insulin staining, to follow the fate of male spleen cells transplanted into female recipients. The female mice that received male donor cells consistently showed Y-chromosome-positive insulin-producing islet cells, indicating that the introduced spleen cells contribute to islet recovery. The current study also showed that the degree of spleen cell contribution is influenced by mouse age at the start of treatment. Spleen cells appear to contribute to islet recovery more in mice who are older and with more advanced diabetes compared with younger mice with less advanced diabetes, in which regeneration of remaining islets may be the dominant mechanism.

###

The research to support the new data was conducted at the NIH laboratory of Eva Mezey, MD, PhD, co-corresponding author of the report. It was funded by the Sjogren's Syndrome Foundation, National Institutes of Health/NIDCR intramural program, Canadian Institutes of Health Research and Canada Research Chair. The three studies published in March 2006 were supported by the Juvenile Diabetes Research Foundation. Faustman's research at Massachusetts General Hospital has been supported by The Iacocca Foundation, which is also supporting a clinical trial program based on her research.

Massachusetts General Hospital, established in 1811, is the original and largest teaching hospital of Harvard Medical School. The MGH conducts the largest hospital-based research program in the United States, with an annual research budget of nearly $500 million and major research centers in AIDS, cardiovascular research, cancer, computational and integrative biology, cutaneous biology, human genetics, medical imaging, neurodegenerative disorders, regenerative medicine, transplantation biology and photomedicine. MGH and Brigham and Women's Hospital are founding members of Partners HealthCare System, a Boston-based integrated health care delivery system.

Scott Strumello <sstrumello@alum.bentley.edu> wrote:

Similar to Joshua, I also questioned the use of BCG, but I did read
the references to why Dr. Faustman and company believe BCG has
potential to work (kindly re-posted by Stacy Lavery). I believe her
explanation is sufficient to warrant further investigation, as we may
now have more evidence to suggest appropriate dosages, how to
administer, and above all, how to measure whether and how it is
working, all things that the Israeli researchers did not have when
their initial studies were undertaken.

Although I believe that many people may blindly believe that this
will be the definitive cure for their child, my suspicion is that
these trials may reveal conditions when BCG will work, and perhaps
when it will not, therefore adding to the knowledge on how to correct
autoimmune diseases, and under what circumstances -- all things that
we do not currently have, therefore I support further research.

Having lived with type 1 diabetes for 30 years now, I have heard all
of these promises before, therefore I believe we should be more
skeptical, but I do believe this is research that needs to be
undertaken, the only difference is that I think we need to be
realistic about what is likely to emerge from this research. Like
Joshua, I would like to see more details from the research team so
that expectations can be set realistically.

Regards,
Scott

--- In nathanfaustmantrials@yahoogroups.com, Joshua Levy
<joshualevy@...> wrote:
>
>
> Thanks very much for posting this! I hope that someone in
Faustman's
> lab will either add a reference to the exact study that cured
someone
> of type-1 diabetes using BCG (even during the honeymoon phase). The
> other quote that I saw made it very clear that their person did not
> have type-1 diabetes at the time of treatment. (But maybe there is
a
> different person.) I suspect that the quote represents a
confabulation
> of different studies. But I would love to be proven wrong on that!
>
> In any case, I think that FAQ answer should be updated with an exact
> source (not the vague "in human studies").
>
> --- Stacy Lavery <stacy_lavery@...> wrote:
>
> > Hi Joshua,
> >
> > I thought I remembered reading something to that effect also, and
I
> > think I've found the quote to which she was referring. It doesn't
> > mention which human study by name here, but in context, it sounds
> > like it was the Israeli study since it mentions two more studies
> > after it, which was the scenario described in the Scientific
American
> > article. She probably read both articles, and remembered both
items
> > together.
> >
> > It's under this link at Dr. Faustman's new website under FAQ:
> > http://www.faustmanlab.com/FAQ.html
> >
> > Here's the whole item, with the item of interest bolded:
> >
> > 7. What is BCG? Is it safe? Why use it?
> > Our human clinical trial program will begin with an evaluation of
> > bacillus Calmette-Guerin (BCG), a generic drug with an impeccable
> > human safety profile that is currently approved for two
indications-
> > tuberculosis and cancer therapy. BCG has been administered to over
> > four billion people since coming to market over 80 years ago.
Similar
> > to the agent we used in mouse studies (CFA), BCG causes the body
to
> > make a natural substance called TNF that helps regulate the immune
> > system.
> >
> > There is ample data to support the use of BCG in the human
diabetes
> > trials. BCG was used many years ago in early-stage diabetic mice
and
> > prevented diabetes. Unfortunately, many compounds work in early-
stage
> > NOD mice, but do not work in late-stage diabetic mice or in humans
> > with advanced disease. BCG was also tried in the past in humans
with
> > new onset diabetes, prior to the knowledge of how BCG actually
works
> > in the body. In the human studies, one diabetic patient was cured
> > with a single dose of BCG, but two subsequent studies with a
single
> > dose of BCG showed no benefit.
> >
> > Compared to when many previous BCG trials were conducted 10 year
ago,
> > the way BCG induces one's own TNF to change disease is now mapped
in
> > animal models and in some human disease. This allows for
thoughtful
> > translation of this intervention to a human trial. We think these
> > early trials of BCG in humans, although encouraging, could not be
> > advanced until we understood BCG's mechanism of action (what it
does)
> > and had a way to monitor the drug's effect in the blood. Think
about
> > this: If we did not know that insulin regulated blood sugars, and
if
> > we did not know how to measure blood sugar, how could we tell
whether
> > insulin actually worked to help diabetics? In many ways, early BCG
> > trials can be seen as similar to injecting insulin without knowing
> > what it really does or how to measure its effects. One of our
major
> > laboratory efforts is to create a method to rapidly and precisely
> > count the disease-causing cells in human blood and to use this
test
> > to evaluate whether BCG can
> > eliminate these cells, and at what dose.
> >
> > Only by conducting a clinical trial will we know if BCG will
work. We
> > chose to test BCG because the agent is readily available and it
works
> > in the human in a similar way (induction of TNF) as the agent we
> > successfully used in the mouse (CFA). In addition, it is
relatively
> > easy to track the killing of the population of autoreactive T
cells
> > targeted by BCG, and we believe that this population of cells may
be
> > the one responsible for the greatest amount of damage to the
islets.
> >
> > Thanks,
> > Stacy Lavery
> > Team Maryland Captain, Join Lee Now Campaign
> > Moderator, Nathan/Faustman Trials Yahoo Group
> >
> > ----- Original Message ----
> > From: joshualevy <joshualevy@...>
> > To: nathanfaustmantrials@yahoogroups.com
> > Sent: Monday, November 20, 2006 7:44:20 PM
> > Subject: [nathanfaustmantrials] Re: Latest Newletter from the lab
> >
> > --- In nathanfaustmantrial s@yahoogroups. com, "rmccully2000"
> > <rmccully2000@ ...> wrote:
> > >
> > > I just read the lastest newsletter on Dr. Faustman's new
website...
> >
> > > http://www.faustman lab.com/News/ FaustmanUpdateFa ll06.pdf
> > >
> > > In the Scientic American article about Dr. Faustman, she
mentions
> > an
> > > Israeli study using BCG single dose at diagnosis as being
partially
> >
> > > successful. Again in the above newsletter, she mentions that one
> > human
> > > was cured using a single dose of BCG, although further studies
were
> > not
> > > as successful.
> >
> > I can not find any place where Dr Faustman said that any type-1
has
> > been cured using BCG. I looked in the newslatter, the SA article,
and
> > another recently published newspaper article. Can you be more
> > specific about where you saw this?
> >
> > I don't believe anyone has been cured using BCG. My doubts are two
> > fold: first, if even one person had actually been cured, every
> > researcher would be all over it. They would be trying slightly
higher
> > doses, slightly lower doses, all kind of varients. Can you imagine
> > the newspaper articles? None of this happened, so I don't think
the
> > cure happened, either. My second reason is this quote below:
> >
> > "Since 1997, researchers in Israel have been injecting BCG, the
> > compound Faustman uses, into a person who was expected to develop
> > diabetes. That patient has remained free of diabetes for seven
years,
> > said Naim Shehadeh, head of the pediatric diabetes clinic at the
> > Technion Israel Institute of Technology. But researchers have been
> > unable to gain additional funding for tests on more people."
> > Source: http://www.cureauto immunity. org/national% 20journal%
> > 201-21-05. htm
> > (about 60% down the page)
> >
> > Note that this person did not have diabetes.
> >
> > Joshua Levy
> >
> >
> >
> >
> >
>
>
>
>
>
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