HDSA Bulletin

HDSA Sponsored Research - Yearly Update

From the Winter 2002 issue of Hopes & Dreams, newsletter of the Illinois Chapter, Huntington's Disease Society of America.

The New Year brought tremendous advances in HD research and particularly in research projects funded by the Huntington's Disease Society of America. Since 1997, HDSA has increased its annual commitment to research from $183,000 to almost $4 million in 2001. Coupled with this amazing growth has been the creation of innovative research programs that have tapped the brightest of scientific minds to both the HDSA Coalition for the Cure and the new Therapeutics Initiative. In turn, these programs have fostered an atmosphere of collaboration unprecedented in the research arena and have brought about innumerable discoveries about Huntington's Disease including ways to delay onset of symptoms, halt the progression of the disease and even reverse brain cell death in animal models. Any one of the projects currently sponsored by HDSA may yield the final piece to the HD puzzle.

In March, a leading HDSA researcher and chair of HDSA's Medical and Scientific Advisory Committee, Christopher Ross, M.D., Ph.D. and his colleagues at Johns Hopkins announced that they had discovered how the HD gene attacks and kills cells. Specifically, researchers discovered that mutant huntingtin "hijacks" a key molecule, CBP, which is vital for activating genes needed for neuronal survival. As Dr. Ross observed, "We haven't yet demonstrated the turnaround in a live mouse model which will be our next step in the research. But we have strong evidence from the cell culture experiments that this is an important mechanism." Dr. Ross was published in the March 23 issue of Science and a complete description of his work can be found in the Spring 2001 issue of HDSA's Toward a Cure.

In May, at the conclusion of the ninth semi-annual Coalition for the Cure meeting, Dr. Jill Heemskirk, Program Director at the National Institute of Neurological Disorders and Stroke (NINDS) announced an historic partnering with the Huntington's Disease Society of America. The new alliance could dramatically change the course of HD research and thus speed new therapies to HD patients. Briefly, NINDS will solicit "supplemental proposals" from scientists and labs already funded by them in order to develop a model or assay that can be used to test compounds that show promise as drug therapies. This dovetails nicely with HDSA's Therapeutics Initiative, which was created this year by HDSA to move exciting research from the lab to the patient more quickly. To date, four HDSA researchers have been granted awards through the Therapeutics Initiative and the alliance with NINDS. But in addition to the incredible opportunity given to HDSA to significantly advance HD research, the partnering with this federal agency also means that Huntington's Disease is now recognized as a "model" disease for other neurological disorders and HD related research has now come to the forefront for funding. You may read more about this historic partnering in the Spring 2001 issue of Toward a Cure.

In June, HDSA Coalition for the Cure investigator Elena Cattaneo, Ph.D. and her colleagues at the University of Milano uncovered a role for normal huntingtin within the brain. Dr. Cattaneo's team found that normal huntingtin protein helps to regulate the production of BDNF, a protein essential for the survival of striatal nerve cells. Mutant huntingtin cannot produce this effect, thus suggesting that the nerve cells in HD patients have less BDNF to ensure their survival. As Dr. Cattaneo noted, "Much additional research must be completed before these findings can help patients, and we want to be clear that this is not a cure. But we are optimistic that our work will help guide the development of new therapies, such as drugs to replace or boost the activity of normal huntingtin, or to increase levels of another brain protein." You may learn more about Dr. Cattaneo's research in the June 14 issue of Science.

In October, HDSA sponsored researcher and newly recognized HDSA Coalition for the Cure investigator, Leslie Thompson, Ph.D. and her colleagues at the University of California (Irvine) made significant headway in halting and preventing the neurodegeneration that is typically a hallmark in Huntington's Disease. By utilizing a class of cancer drugs, known as histone deacetylase (HDAC) inhibitors, Dr. Thompson and her team were able to block several proteins found in Huntington's Disease. Using the Drosophila (fruit fly) model, researchers found that the chemotherapy drugs prevented brain cell death that is caused by the mutant HD gene, even after the flies began exhibiting symptoms of HD. The chemotherapy drugs used in this research have not been tested on HD patients to date. But given the fact that they have already been approved by the FDA for use in some forms of cancer, it may harbinger a swift move to testing the efficacy in HD animal models and ultimately human clinical trials. As Dr. Thompson noted, "We are beyond excited." To read more about Dr. Thompson's groundbreaking work, please see the October 18th issue of Nature.

In November, the tenth semi-annual meeting of the HDSA Coalition for the Cure met in Toronto, Ontario to discuss the new research generated by Dr. Thompson and her colleagues as well as to review progress in other ongoing projects. Among the highlights of the two day conference were: Dr. Erich Wanker, an HDSA Coalition for the Cure investigator, at the Max-Delbruck-Center Institute for Molecular Genetics (Berlin, Germany), reported that he and his group have screened more than 180,000 compounds using high throughput screens. From this intensive effort, 70 chemicals have been identified that appear to inhibit the development of protein a ggregates in the brain. (See HDSA's The Marker magazine Research 2000 for more on Dr. Wanker's work)

Dr. Michael Hayden, an HDSA Coalition for the Cure investigator at the University of British Columbia/Centre for Molecular Medicine and Therapeutics (Vancouver, BC), reported that his group has identified a new protein that they termed HIPPI. This new protein interacts with the protein HIP-1 (Huntingtin interacting protein 1) may be tied to cell death in HD.

HDSA Coalition for the Cure investigator Dr. Gillian Bates, at Kings College London (London, England) has begun to test the HDAC inhibitors in HD mouse models in order to determine whether they can replicate the promising results demonstrated with the Drosophila (fruit fly) model in preventing cell death. These are the same inhibitors that were used by Dr. Leslie Thompson in her most recently published work in Nature.

Dr. Steven Hersch, an HDSA Coalition for the Cure investigator at Massachusetts General Hospital (Boston, MA) reported on progress made in using different anti-inflammatory compounds to determine whether they have a potential in treating HD.

The HDSA Coalition for the Cure was also pleased to introduce two new members into its esteemed ranks. As earlier noted, Dr. Leslie Thompson of UC Irvine was formally inducted into the Coalition and is an HDSA success story in her own right. Starting with an HDSA Initiative Grant in 2000, Dr. Thompson's work has wrought startling new avenues for research into Huntington's Disease and her most recent work with HDAC inhibitors in preventing cell death has earned her a place in the HDSA Coalition for the Cure.

Dr. Ron Kopito from Stanford University (Stanford, CA) was also granted recognition in the Coalition. Dr. Kopito's work will test the effect of huntingtin aggregation on the ubiquitin proteasome system (UPS), which is the main method by which cells eliminate unwanted proteins. Dr. Kopito will use both cell cultures and HD animal models to test his theory of a possible biochemical linkage between aggregation of mutant huntingtin and cell death. The proposed research will also utilize a new real-time assay (test) for huntingtin aggregation in a screen of compounds that may be effective in interfering with the structural changes that underlie the protein aggregation behavior and its toxicity.

The Huntington's Disease Society of America is pleased to welcome both Dr. Thompson and Dr. Kopito to the HDSA Coalition for the Cure.

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Created: April 6, 2002
Last updated: Dec. 2, 2010