Impressive progress has been made by CHDI, a non-profit drug development organization devoted to HD. Dr. LaVonne Veatch Goodman presents highlights on drugs being developed for HD reported at this year's CHDI conference.

The Conference HDI held its 2ndannual conference the first week of February 2007. During a packed three days, drug development specialists from CHDI and many for-profit companies reported on the progress they have made this past year towards developing drugs for Huntington's. Acting urgently, they have come a long way on several fronts. I left the conference with more optimism than I've felt in a long time. For a broader report on the conference, I recommend Jim Tretheway's article at HD Lighthouse. For background on CHDI, please see my previous article on CHDI at HDDW.

Drug highlights by drug type from near to far term.

  • SSRI antidepressants - Scientists from Dr. Chris Ross's lab presented HD mouse results showing that sertraline (Zoloft®) is neuroprotective and increases BDNF to normal levels. BDNF is a natural chemical in the brain that promotes nerve cell health and which is decreased in HD. The scientists suggested that HD gene positive individuals consider taking this drug. I would go further and recommend that HD gene positive individuals take this drug (or other SSRI containing drugs) as treatment for HD.
  • Coenzyme Q-10 (Co-Q10) improvements - Dr. Bill Shrader from Edison Pharmaceuticals reported on improved versions of Co-Q10 that are both stronger and more able to get into brain. One of these agents was originally developed for another disease, but it is also active in screens for HD. This drug is almost ready for a Huntington's clinical trial now, and it would make sense to include it in the upcoming HSG trial (2CARE) of regular Co-Q10. If this doesn't happen, I expect Edison to do a clinical trial on their own. I will keep a close watch on this and report any news.
  • Adenosine A2a antagonists - Dr. Daniela Brunner from PsychoGenics Inc. presented encouraging preliminary results on agents that antagonize (partially block) A2a receptors, which are overactive in HD. A2a receptors are natural chemicals in the brain that play a role in stimulating nerve cells. (A2a receptors are also present in other parts of the body.) Since A2a receptors are overactive in HD, a drug that partially blocks them may be helpful. A drug of this type recently completed clinical trial in the U.S. for Parkinson's Disease. PsychoGenics is testing this drug on HD mice. If it works in mice, it could be moved quickly into clinical trial. It will take 2-3 years to complete the clinical trial and get full FDA approval, but if early results are promising, this drug could be available to HD people much sooner either off-label or through an FDA-approved early access program.
  • Creatine improvements - Dr. Noa Zerangue from XenoPort, Inc. reported on improved versions of creatine that are better able to get to brain. They figured out a way to put the creatine inside a molecular package that protects it from being degraded before it gets to brain, and lets it slip into brain cells more easily. This drug is a year or two away from clinical trial assuming all next steps are successful.
  • HDAC inhibitors - Dr. Jeffrey Besterman from MethylGene reported that drug candidates have been identified and are ready to be tested in mice. The term "drug candidate" refers to a potential drug that is at the starting gate. Companies often identify multiple drug candidates that work in similar ways and test them in parallel to find the one that works best. If all goes well, a realistic estimate for drug to people is more than five years.
  • Caspase 6 inhibitors - Building on the very important work of Dr. Michael Hayden and colleagues, Dr. William Janzen from Amphora Discovery Corporation reported progress on identifying potential drugs of this type. He estimates it will take another year before he can provide drug candidates to Dr. Hayden and others for testing in mice. These drugs are a little behind the HDAC inhibitors.

Comments Over the years, I have found that going to Huntington's conferences is a little like riding a roller coaster. I remember the tears of joy I shed when gene discovery was announced, and several years later my enthusiasm after hearing the first reports of benefit in mice induced by minocycline, Co-Q10, and creatine. And now, on almost a daily basis there are reports of one or another treatment that works in yeast, or flies, or mice. But at the end of the day, I would always come back to the ground level reality that nothing terribly good was in sight for the people I care about. This conference was a little different. I think I see some light at the end of the tunnel. And though I can't know how far away it is (and it's always longer than we hope), I believe effective treatments are coming.


Graham RK, Deng Y, Slow EJ, Haigh B, Bissada N, Lu G, Pearson J, Shehadeh J, Bertram L, Murphy Z, Warby SC, Doty CN, Roy S, Wellington CL, Leavitt BR, Raymond LA, Nicholson DW, Hayden MR. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell. 2006 Jun 16;125(6):1179-91. PubMed abstract

Hockly E, Richon VM, Woodman B, Smith DL, Zhou X, Rosa E, Sathasivam K, Ghazi-Noori S, Mahal A, Lowden PA, Steffan JS, Marsh JL, Thompson LM, Lewis CM, Marks PA, Bates GP. Suberoylanilide hydroxamic acid, a histone deacetylase inhibitor, ameliorates motor deficits in a mouse model of Huntington's disease. Proc Natl Acad Sci U S A. 2003 Feb 18;100(4):2041-6. PubMed abstract

Links to related material

CHDI website

Previous HDDW article on CHDI

Jim Tretheway's conference report at HD Lighthouse

HSG 2CARE trial

Edison Pharmaceuticals website

PsychoGenics website

XenoPort website

MethylGene website

Amphora Discovery Corporation website