From Dr. Marsh Miller via Steve Ireland's computer at the convention. I
apologize if you've already seen her response.
Dave

Illinois Chapter TEAM HOPE-Walk For A Cure
http://www.HDWalk.org
Ill. Chapter-HDSA Web Page
http://www.hdsa-il.org
Sponsor Dave & Susie's Walk
http://www.firstgiving.com/DaveandSusie
----- Original Message -----

From: "Steve Ireland" <stevei@...>
To: <HUNT-DIS@...>
Sent: Sunday, June 07, 2009 7:54 PM
Subject: Re: What does everyone think??


> This sounds like another piece of the puzzle but as usual with press
> releases it is overstated. First of all it's not true that "No one had the
> vaguest notion of what was the cause of the brain damage." In other words,
> everyone else's research is crap but this guy has uncovered the truth? I
> don't think so. HD has been slow to give up its mysteries but more and
> more
> has been learned every year since the gene was discovered. We know a LOT
> about how the HD protein causes brain damage.
>
> Second, HD interacts with dozens of proteins and some of that interaction
> results in pathological processes. This researcher has identified a new
> one.
> Good work but he's not solving a mystery.
>
> Third, the idea that aggregates are not the problem, it's the soluble
> protein is not new. We got that. HD pathology needs to be addressed
> upstream
> from this. The longer term goal is to silence the HD gene and the shorter
> term goals are to find medications that address early pathologies.
>
> Fourth, there is no part of the brain which is unaffected by HD. And it
> affects muscle tissue as well. Yes, the greatest damage is in the striatum
> and this new finding may explain why but clearly it's damaging other parts
> of the brain. Stopping the damage to the cortex is just as important!
>
> Press releases drive me crazy. Researchers, universities, medical colleges
> are all hoping for good publicity and more donations and grant money so
> they
> overstate the importance of their work but it puts the HD community on a
> roller coaster. Barb is right, cautious optimism is the best attitude to
> take.
>
> Research is slow and cumulative. Sometimes there are big breakthroughs but
> those are followed by years of hard work. The caspase six research was
> three
> years ago. Researchers have been trying to discover or develop a caspase
> six
> inhibitor ever since. Then they'll test it in the mice. Everything takes
> time.
>
> It's good though that things are happening in parallel. We're waiting for
> a
> caspase six inhibitor but we have four Phase III clinical trials going on
> and more candidate drugs for clinical trials.
>
> And I have to disagree about years of false hopes and dead ends. I think
> that HD research, at least in the eleven years I have been following it,
> has
> been remarkably cumulative. Lots of problems have been explored but HD is
> a
> multi-hit disease and there ARE lots of problems. I think that some
> medications have been tried that weren't specific enough to the target but
> that just means that we need to do drug development and get better
> medications. We now have the funding for that now and pharmaceutical
> companies are taking a new interest in HD.
>
> One of the reasons I wanted to write about the research is to help put it
> in
> perspective for the community. If you follow press releases - "My new
> finding is THE answer and it'll lead to the cure" then HD research looks
> like a roller coaster of hope and disappointment. If you realize that HD
> is
> a complicated puzzle and it takes years of solid research to fill in the
> puzzle and develop good drugs then you can feel encouraged by the progress
> being made.
>
> I wish things DID go faster, but they don't. I am hoping that new
> treatments
> will be available soon and that they will buy us time for better
> treatments.
>
> Marsha
>
> -----Original Message-----
> From: Huntington's Disease Discussion [mailto:HUNT-DIS@...]
> On Behalf Of Kelly Fox
> Sent: Sunday, June 07, 2009 7:08 PM
> To: Steve Ireland
> Subject: What does everyone think??
>
> Scientists uncover culprit in Huntington's disease
>
> June 4, 2009 - 2:01pm
> By LAURAN NEERGAARD
> AP Medical Writer
>
> WASHINGTON (AP) - Scientists have solved a mystery surrounding a
> horrific illness: Why people with Huntington's disease harbor a faulty
> protein throughout their bodies but it destroys only certain brain cells.
>
> The discovery may provide a long-awaited target for developing
> treatments for the incurable killer _ and also may have ramifications
> for more common brain diseases like Alzheimer's.
>
> "Up until now, nobody had the vaguest notion of what was the cause of
> the brain damage and the death," said Dr. Solomon Snyder of Johns
> Hopkins University, whose team reported the findings in Friday's edition
> of the journal Science.
>
> "This is a significant step forward," said Dr. Walter Koroshetz, deputy
> director of the National Institutes of Health's brain division.
>
> Huntington's is a rare inherited disease _ there are an estimated 30,000
> U.S. patients _ that typically strikes in the late 30s or early 40s.
> What starts as uncontrollable twitches and jerks and deterioration of
> mental abilities inexorably worsens until patients can barely eat, speak
> or walk. Death occurs a decade or more after symptoms begin.
>
> One mutated gene is the cause. A child of a Huntington's patient has a
> 50-50 chance of inheriting that gene, and anyone who does will develop
> symptoms at some point if they live long enough. Scientists discovered
> the gene in 1993, giving families the hard choice of whether to be
> tested to learn who escaped that fate and who didn't.
>
> But 16 years later, there is only one treatment to ease the writhing
> movements and little progress toward the bigger goal _ finding some way
> of slowing or stopping the disease from carving a hole in patients'
> brains.
>
> Enter the new research. The bad Huntington's gene creates a faulty
> protein that's found in all cells. Yet the only cells that die are
> certain neurons, mostly those in a movement-controlling brain region
> called the corpus striatum that by the time patients die is so ravaged
> that it's tissue-paper thin.
>
> Why? A second protein is the culprit, Snyder's team discovered. It's a
> little-known molecule named Rhes that is found almost exclusively in the
> striatum. When Rhes mixes with the mutated Huntington's protein it
> sparks a chemical reaction, the researchers reported.
>
> First came a simple experiment: They used human embryonic cells and
> brain cells taken from mice. To each, they mixed in different
> combinations of the mutated Huntington's protein, its normal version,
> and Rhes. Only when both the mutant protein and Rhes were in the same
> cells did those cells start dying.
>
> Then the researchers teased out just what made the chemical reaction,
> named sumoylation, so toxic. It seems that cells may try to deal with
> the mutated protein by clumping it out of the way, almost like creating
> a garbage heap. Adding Rhes led to less clumping along with cell death,
> suggesting that it's the soluble form of the faulty protein that's
> dangerous.
>
> And that's the connection to other brain-destroying diseases like
> Alzheimer's. Most are distinguished by clumps of some type of faulty
> protein, and there's a raging debate among scientists about whether the
> clumps, also called "aggregates," are the cause of brain destruction or
> a frantic attempt by the brain to save itself.
>
> "The answers in one disease may have implications for another," noted
> Koroshetz of NIH's National Institute of Neurological Disorders and
> Stroke. "There's been people on both sides of the fence. This story
> plays to the role of the aggregates as not being the major problem but
> the soluble protein as being the major problem."
>
> Dr. Nancy Wexler of the Hereditary Disease Foundation, who helped lead
> the Huntington's gene discovery, called the work a "fabulous experiment"
> and praised the Hopkins team for quickly publishing the Rhes reaction so
> that other researchers could start hunting ways to block it.
>
> "This is a very promising avenue," she said.
>
> One next step is to see whether removing Rhes from mice with
> Huntington's disease slows or prevents the brain cell death without
> causing too many side effects. If so, the quest would be for a drug to
> block that protein.