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Tetrabenazine is effective to treat the excessive involuntary movements of Huntington’s

A drug dramatically eases one of the most disabling symptoms of Huntington’s disease, involuntary writhing movements known as chorea.

The medication is Tetrabenazine.

In a randomized, controlled study conducted in 84 patients at 16 sites around the nation, doctors found that the medication cut down involuntary movement on average by about 25 percent, with many patients experiencing a greater improvement. Overall, patients who received the medication were six times as likely to be considered by their doctors to have improved considerably, compared to participants who received a placebo.

“ Neuroleptic drugs like Haloperidol ( Haldol ) are currently in widespread use in the United States to suppress chorea, but the effect of these drugs on chorea has never been studied in a systematic way, and they have a number of troublesome side effects, such as blunting of personality, loss of voluntary movement, and hindering balance. Our study showed that Tetrabenazine, when appropriately dosed, can decrease chorea without causing those side effects,” said Frederick J. Marshall, at the University of Rochester Medical Center who led the study conducted by the Huntington Study Group.

. Tetrabenazine was originally developed in the 1950s to treat psychosis, but was quickly pushed aside by more effective medications. But doctors in the United Kingdom found it to be effective to treat the excessive involuntary movements of Huntington’s, and it is approved for use in several nations. In the United States, Tetrabenazine is designated as an “orphan drug” by the FDA since it’s targeted to a disease directly affecting fewer than 200,000 people in the nation.

The symptom that Tetrabenazine treats – involuntary, writhing movements of the limbs, face, and sometimes the entire body – is the hallmark symptom of Huntington’s disease, an inherited neurodegenerative disorder that worsens as brain cells known as medium spiny neurons are killed off by a mutant protein. The disease brings with it an array of other difficulties as well, including cognitive problems, changes in personality, and psychiatric problems like depression. As many as one-quarter of patients with the disease attempt suicide, and many suffer from progressive cognitive decline. Unlike Alzheimer’s disease, where patients usually lose their memory and insight into their disease at some point, most Huntington’s patients understand exactly what is happening to them throughout most of their illness.

The disease usually strikes people in their 30s and 40s, though some patients are affected as early as childhood, while others aren’t affected until their older years.
Virtually everyone with the disease had a parent with the disease, and children of a person with Huntington’s have a 50-percent chance of inheriting the disease.
Thirteen years ago the gene that causes the disease was identified by scientists, and now a simple blood test can tell people whether they will develop the disease or not. But since there is no way known to prevent the disease or slow its progression, and for other reasons as well, many patients decline the test, instead waiting to see if they develop symptoms like the ones they witnessed in a parent. Patients usually live for 15 to 20 years after the onset of symptoms.

Viewed simply, in some ways Huntington’s disease is the opposite of Parkinson’s disease, where damage to the neurons that produce dopamine hinders a person’s ability to move and cause other symptoms. In Huntington’s, too many dopamine signals result in random, uncontrollable movements. Tetrabenazine inhibits a molecule known as vesicular monoamine transporter 2 ( VMAT2 ), an action that ultimately blocks the release of dopamine.

“ This is not a wonder drug for Huntington’s. It doesn’t address the psychiatric or cognitive problems, for instance. But there are some patients for whom chorea is clearly a devastating feature of the illness.” said Marshall, who is chief of the University’s Geriatric Neurology Unit. “ Easing chorea could help patients with tasks they normally struggle with, such as eating, driving, grooming, and walking.

About a quarter of patients reported sedation, fewer than 10 percent of patients had motor restlessness, and fewer than 5 percent had motor slowing or depressed mood. Side effects generally resolved with downward adjustment of the dosage. Of concern, one patient committed suicide during the study. Because of the high rate of suicide attempts in patients with Huntington’s disease, all patients deserve close follow-up.

Source: University of Rochester Medical Center, 2006