1999 National Convention Recap

By Tom Caldwell, Tucson, Arizona (TECaldwell@email.msn.com)


From the Fall 1999 issue of Hopes & Dreams, newsletter of the Illinois Chapter, Huntington's Disease Society of America.

Financial Aspects of Research

At the 1999 HDSA convention, Dr. Christopher Ross, Chair of HDSA's Medical/Scientific Advisory Committee, tried to put the financial side of our research efforts into perspective. Last year's research budget was $1.5 million; next year's will be $1.8-$2 million. It mostly goes into two programs.

Research Grants and Fellowships

The first of these is research grants and fellowships. This money goes for small projects which are useful research in their own right, but which are designed to get new scientists hooked on HD research and keep them interested. In 1997, we spent $260,000; in 1998, $380,000; and in 1999, $620,000.

Recently, the Smith Family Fund has donated $250,000 for clinical and basic science, and it is being spent in this program.

Coalition for the Cure

The second is the Coalition for the Cure, working to accelerate HD research. In 1997, it was funded at $450,000; in 1998, $750,000; and in 1999, $1.25 million. A $250,000 "matching grant" has been received from an anonymous donor to be used in this program.

The Chapter Research Alliance has raised $240,000 to help fund these programs. The chapters include:

Central Ohio
Connecticut
Greater Los Angeles
Illinois
Indiana
Kentucky
Massachusetts
Mid-Michigan
Minnesota
Northeast Ohio
North Carolina
Northern California
Oklahoma
San Diego
St. Louis
Upstate New York
Western Pennsylvania
Wisconsin
Georgia ($50,000)
Southern Florida ($60,500)
Delaware Valley ($75,000)

Keynote Speeches

Michael R. Hayden, MD, PhD

Michael R. Hayden, MD, PhD, is the Director of the Center for Molecular Medicine and Therapeutics, U. of British Columbia, Vancouver, Canada. He started his career in South Africa and has been involved in HD research for more than 20 years. He will be the recipient of the Guthrie Family Humanitarian Award this year.

He said there is no gene like the HD gene. The number of CAG repeats do correlate somewhat with age of onset. Researchers are currently looking at mice, worms, and flys which have been genetically engineered to have the HD gene. They have found that cell death starts in a part of the brain called the caudate nucleus. How the cells die is not certain yet. The HD gene causes a protein, huntingtin, to be produced. This protein is essential to life, at least in mammals--mice genetically engineered to lack the HD gene die while still in the womb. Huntingtin gets smaller as cells age. It gets cut up in a process called "cleavage". The cleaving is done in two different parts of the protein by members of the caspace chemical family.

As huntingtin gets smaller, the pieces become more toxic, and the smaller fragments tend to migrate into the cell's nucleus. Preventing cleavage prevents toxicity. Some of the fragments coallesce into clumps called "aggregates". At first, the aggregates were thought to play a role in cell death, but subsequent research has cast doubt on that model. Brains of HD mice show evidence of cleavage and resultant neuronal degeneration. The aggregates are not there in the earlier stages, but there is still massive neuronal loss. The more popular current model is that the protein is cleaved producing aggregates and cell death; the aggregates may or may not contribute to cell death; cell death causes the symptoms we call HD.

In the animal model, HD is caused by mutations similar to those in humans. A corrective gene can be made a part of the animal's genome. This protective gene causes some of the caspaces to be inhibited. When this happens, the cells don't die as fast.

Dr. Hayden then went on to talk about therapies. He said the big drug companies are now interested in HD. There is now significant hope. Several drugs with great promise should be ready for testing within the next 10 years.

Dr. Francis Collins

At the HDSA National Convention in Washington, DC, Dr. Francis Collins, Director of the Human Genome Project spoke on the subject of Directions in Genetics. The Human Genome Project was to be a 15 year long study to totally discover and categorize every gene in the human body, a very lofty project. The 15 year prediction for the duration of the project has been shortened to 10-11 years due to the introduction of a unique computer program that can find genes faster than ever thought before.

Why is the project relevant to HD if the gene has already been found? Dr. Collins gave four reasons: 1) To try to understand the differences in onset of the disease; 2) For the comparison of genomics between humans and animals (important for testing of new drugs); 3) We need to understand the function of the protein produced by the HD gene; and 4) Understanding the social and ethical problems associated by the discovery of not only the HD gene but all genes.

Dr. Collins took us through the process of project in general by introducing the human DNA sequence and how they are deducing the text of the book of life. Currently, they have finished 18% of the genes and hope to be done by the year 2002. In addition, they are attempting to catalog the human sequence variation, which is a new goal for the human genome project. This project will make it easier to understand why some genes vary from what they're supposed to do. Additionally, it will provide a resource for physicians, who, for the most part, are not too knowledgeable or haven't been too deeply introduced to the area of genetics.

Dr. Collins stressed the importance of assuring that our genetic information cannot be used against us by an insurance company. He mentioned his two pillars of belief: fair use of information with no discrimination and restriction of genetic information to only those who need it for health reasons. He is calling for broad support for laws banning genetic discrimination and stressed the importance of supporting the "Patient's Bill of Rights" in the Senate and strongly encouraged our support. Also, he stressed the need for parity of physical as well as mental benefits, commenting that HD is a brain injury and NOT a mental disease. As an aside, THIS comment received a standing ovation. Dr. Collins entertained a few questions including one in which he was asked if he supported stem cell research, banned for some time by the Federal Government. He could not officially comment on the question, but, off the record, he supports ANY research that will find a treatment or cure for HD.

Board of Directors Meeting Recap

At the 1999 convention, I attended two sessions that were devoted to HDSA organizational matters. The first was "Meet HDSA's Leaders". The main thing I got out of that one was that we will be a $5 million organization by the end of the year and that we've increased our research funding 500% in the last two years to $2.5 million.

The second session was the board meeting. From it I learned that we now have net assets of $1.3 million, enough to keep the Society afloat for seven months, even if donations absolutely dried up. This is the best situation I've seen the Society in for 22 years.

On the research front, the Huntington Study Group is going ahead with PHARO, a project studying age of onset. As some of you know, a major HDSA effort is to establish "Centers of Excellence"--major HDSA treatment centers--around the country. To date, 18 letters of intent have been received from prospective Centers. We won't be able to fund them all, but 15 have been asked to submit formal proposals.

A chapter in North Carolina has been given a provisional charter, meaning they will be able to function as a chapter but will be on probation for a couple of years until they demonstrate their ability to meet our requirements on a continuing basis. This fills an important geographical gap; until now, there have been no chapters between Washington, DC, and Georgia.

For some reason, perhaps the exciting research news and/or our financial success, people who haven't donated in 3 or 4 years and donating again, some at the $1000 level. Perhaps success breeds success.

A series of full-page HD ads should start appearing in July in several well-known national magazines.

Several meeting locations were announced: The 2000 leadership conference will be in San Diego, the one in 2001 in Phoenix. The 2000 convention will be in Orlando, FL and 2001 in either Dallas, San Diego, or Phoenix.

Clinical Trials

The session began with a tribute to Jack Penney whose death is a great loss to the HD community. Nancy Wexler played a tape of Dr. Penney working on the Venezuela project.

Current or planned clinical trials and related research were described:

1. Care HD - (CoQ10 and Remacemide evaluation in HD)

Enrollment ended a year ago for this study. Each subject will be followed for 2.5 years. Active participation will end at the end of 2000 and then the data will be analyzed.

2. RID-HD (Riluzole Dosing in HD)

Riluzole has an anti-glutamatergic application. 60 subjects will be followed to assess safety and tolerability in HD patients.

3. Creatine: Safety, Tolerability and Dose-Finding (Beal, Hersch)

Beal and Hersch are currently studying creatine in mice and have submitted a proposal to study this in HD patients to the NIH Office of Alternative Medicine. Creatine is considered a health supplement so it is not regulated by the FDA. Nevertheless there are potential risks and some concerns have been raised in regard to juvenile athletes.

4. Transplants (Europe)

France will be presenting the results from their pilot study soon.

5. U.S.-Venezuela Project

This longitudinal study will examine issues such as how to tell the age of onset, how CAG repeats are associated with age of onset, the progression of the disease in homozygotes (people with two copies of the mutant huntington's gene), and development of illness in people in the grey area.

6. Huntington's Study Group's United Huntington's Disease Rating Scale (UHDRS) Data Base

3,000 people are enrolled world wide in this study. 1,000 will be followed over four years. Researchers will be looking at the natural history of decline, the development of specific symptoms, and weight loss. This study will allow researchers to figure out how many people would need to be enrolled for researchers to do various clinical trials.

7. PHAROS - Pilot Huntington's At Risk Observational Study

There are 38 sites participating in this study, 36 in the U.S. and 6 in Canada. Enrollment starts this month (June 1999). 1000 at risk individuals from ages 30 to 55 are being sought. Participants can't know or want to know their gene status. The participants will be examined every nine months for three or more years by independent clinicians who will not be involved in their care. The goal is to understand what happens as the people go from being healthy to developing symptoms of HD.

8. Predict-HD - Neurobiologic predictors of HD

225 people ages 30-54 with CAG repeats of 39 and above will be studied at 15 sites. The study will involve intensive neuropsychological studies as well as MRIs, and PET scans of the brain. Questions to be answered include when does HD begin, how does it progress, and how does it affect behavior and cognition. The ultimate goal of this study is to learn when doctors should start administering treatments when they become available.

9. MAOPS - Modifying Age of Onset Peer Study

The Huntington's Study Group is looking for genes that may modify the age of onset. They will be studying 500 sibling pairs.

Dr. Nancy Wexler closed by saying that the research is very promising. Frielander's study with caspace one inhibited mice is very exciting because it shows that something can be done


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Created: Oct. 9, 1999
Last updated: Sept. 14, 2010