In this article published in the July 25 Journal of Neuroscience, Dr. Bezprozvanny and colleagues show that tetrabenazine is neuroprotective. It delays onset of disease symptoms and saves neurons in the YAC mouse model of Huntington's. They also show that L-dopa, a drug commonly used in Parkinson's is harmful. This is a great example of translational research, or laboratory experiments that can lead to application in HD people. Dr. Goodman hopes that these results will encourage greater use of this drug and add incentive for prompt FDA approval.

Simply Put

Tetrabenazine delayed onset of motor symptoms and is neuroprotective, saving brain cells in the HD YAC mouse.

Why is it Important? Tetrabenazine is clearly helpful for treating chorea (often with dramatic benefit) in many Huntington's people [Huntington Study Group 2006]. However, doctors and patients are often hesitant to try this drug due to fears that it will increase the already elevated levels of depression and suicide in HD people. In a previous study [Kenney C 2006], Jankovic and colleagues gave compelling evidence that tetrabenazine depression can be treated and controlled in the vast majority of patients, causing only 3% of 518 patients to stop the drug. The new results by Bezprozvanny and colleagues should increase our interest and comfort level in using this drug. In my opinion, the safest approach for tetrabenazine use is to treat all tetrabenazine patients with antidepressants, and to have frequent physician/patient followup to look for and treat this important side effect.

The Research Goal: The original goal of this research was not to study tetrabenazine but instead to use this drug (and others) to study how the dopamine system malfunctions to cause brain cell death in HD. The unanticipated result of these experiments is that tetrabenazine benefit was far greater than expected.

The Method: YAC HD mice were given L-dopa (which increases dopamine), or a combination of L-dopa and tetrabenazine (which decreases dopamine) for 10 months. Drugs were given months before the mice developed symptoms and continued for months past the time of symptom onset for the YAC mouse. Drug effects on motor symptoms and brain morphology (how the cells look under a microscope) of these two groups were compared to YAC and normal mice who received no drug.

The Results: For motor symptoms, L-dopa alone caused worsening of motor symptoms in the YAC mouse. Adding tetrabenazine to L-dopa prevented onset of motor symptoms (on several test measures) for months beyond the usual onset. For brain morphology, untreated YAC HD mice had lower neuron cell count (due to death of cells) when compared to normal control mice. L-dopa lowered neuron cell count (more brain cell death). When tetrabenazine was added to L-dopa, it gave a neuroprotective benefit; fewer brain cells were lost than in the usual YAC mouse.

Impact on FDA Approval: Tetrabenazine is still waiting for drug approval in the U.S. while families are spending $200 (or more) per month to obtain it for their loved ones. Many who would like to use it can't afford it.

When the drug came up for FDA review, Prestwick, the sponsoring company received an "approval letter". This means that the FDA required that certain (not publicly named) questions be answered before drug approval. This step requires positive review and recommendations from a neurology specific FDA advisory committee. Though it has been more than year since an approval letter was generated for tetrabenazine, the necessary FDA advisory committee session hasn't been scheduled. We can hope this latest research will spur the company, HSG leaders, and the FDA to prompt action on this drug.

The Report


Huntington Study Group. Tetrabenazine as antichorea therapy in Huntington disease: a randomized controlled trial. Neurology. 2006 Feb 14;66(3):366-72. PubMed abstract

Kenney C, Hunter C, Mejia N, Jankovic J. Is history of depression a contraindication to treatment with tetrabenazine?. Clin Neuropharmacol. 2006 Sep-Oct;29(5):259-64. PubMed abstract

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