HDSA 2008 convention session: Potential new therapies

HD Lighthouse Contributing Editor's Comment: I was particularly encouraged by this workshop at the HDSA convention.  We have some very promising drugs in the pipeline.

-- Marsha L. Miller, Ph.D.
Posted to the HDL: 07-10-2008

Workshop speakers, from left to right:
Xiaowei Jin, Ph.D., CombinatorX; Sarah Noonberg, M.D., Ph.D., Medivation; Joakim Tedroff, Ph.D., M.D., Neurosearch; and Jeffrey Stack, Ph.D., Vertex

Potential New Therapies

Neurosearch: ACR-16

Dr. Joakim Tedroff, representing Neurosearch, reported that ACR-16, a dopamine stabilizer, is already in Phase III clinical trials in Europe and is poised to start Phase III trials in the United States.

ACR-16 is a small molecule belonging to a pharmacological class called dopamine stabilizers. It can enhance or inhibit activity depending on the initial level. In other words, if dopamine activity levels are too high, ACR-16 can decrease them, but if activity is too low, ACR-16 can increase it. This contrasts with neuroleptics where a reduction in activity of this important neurotransmitter occurs, regardless of initial level.

ACR-16 appears to work by strengthening cortical control of the basal ganglia. The striatum, which is part of the basal ganglia, is the brain's autopilot. Once we have learned a behavior, we need not give it our full attention. The striatum will control the activity while our cortex is thinking about something else. Once the striatum begins degenerating in HD, the cerebral cortex loses control of the basal ganglia.

The results of a Phase II study

.... Dr. Tedroff advised us to watch the HSG web site for an announcement of where the phase III trial will be recruiting in the U.S. and Canada. We will also have the news on the Lighthouse and the HDSA web sites.

CombinatoRx: two promising combinations

Dr. Xiaowei Jin from CombinatoRx reported on two promising combinations that have been identified through their high throughput screening process. CombinatoRx is working collaboratively with CHDI to find new combinations of already approved drugs which together will act as a treatment.

CombinatoRx is using two assays. One is ....

Medivation: Dimebon

Dr. Sarah Noonberg from Medivation discussed Dimebon as a potential treatment. Dimebon is a antihistamine that was used in Russia. Russian scientists discovered that it had neurologic properties. Medivation, a biopharmaceutical company formed in 1993, licensed the drug and begin studying it for Alzheimer's disease. A Phase II trial with AD patients showed some benefit and a Phase III trial is underway.

Because of similarities between AD and HD, it seemed worthwhile to also look into Dimebon as a treatment for Huntington's. Dimebon promoted neuronal survival in a fruitfly model of HD. A brief Phase I trial showed that Dimebon was safe and well tolerated for HD patients. A Phase II trial for Huntington's patients followed.

Dr. Noonberg reported that the results of the Phase II trial of Dimebon in HD will be announced in July. The trial was conducted to see if Dimebon was safe and well tolerated in Huntington's patients over a three month period. They will also look for any indications that it improves symptoms although the period may be too short to tell whether or not the drug is effective (effectiveness is examined in Phase III trials).

The brain has a high need for energy. The mitochondria are like 'tiny gas stations' to provide fuel to cells so that they can carry out their normal function. The brain has about 100 billion brain cells and each of these has 1000 mitochondria. Dimebon appears to have a potent effect on mitochondria function.

Dr. Noonberg hypothesizes that the good results seen so far in clinical trials of Dimebon in Alzheimer's patients will be found for HD patients as well. Both involve progressive neurodegeneration, both involve abnormal protein accumulation, and both have abnormal mitochondrial function.

Medivation's goal: If it's safe and effective, let's get it FDA approved and out to HD patients!

Vertex: a new collaboration with CHDI

Dr. Jeffrey Stack from Vertex reported that the collaboration with CHDI to develop drugs to treat HD is just getting started but....