Huntington’s Disease is a serious,
progressive disease that involves degeneration of part of the brain.
In particular, there is loss of neurons and development of
gliosis in the striatum. The disease is named after George Huntington,
who described it in 1872.
Disease can be diagnosed by genetic
testing. There has been a lot of progress in
understanding exactly what
goes on in the brain, as the disease progresses.
Still, nothing close to a cure has been found.
is possible to treat some of the symptoms. Up until now, such
treatments have been only minimally effective. Death usually
occurs 10 to 20 years after symptoms first appear. Death
usually occurs due to pneumonia. The suicide rate are 7 to 10
times greater than that in the general population.
some non-US countries, tetrabenazine
has been available for a while (35 years). However, the FDA
in the USA requires pre-approval testing that is more stringent than in
most countries. It has been difficult to do testing that is
acceptable to the FDA, because good testing requires large numbers of
patients. The disease is sufficiently rare (4 to 10 cases per
100,000 persons), that it is a challenge to get enough patients.
Also, the disease progresses slowly, so there isn’t a quick
way to know if the drug is working.
On 15 August,
2008, the FDA announced that tetrabenazine
has been approved for the treatment of Huntington’s Disease.
works by inhibiting the action of a protein in the brain, called Vesicular
Monoamine Transporter 2. (VMAT2). This is a protein
that acts to move chemical messengers inside of nerve cells.
VMAT2 is found mostly in the brain. There is a
similar protein, VMAT1, that is found in the rest of the body.
This is convenient, because we don’t want the drug to affect
anything outside of the brain.
take tetrabenazine undergo relative depletion of these chemical
messengers. The one that is important in Huntington’s Disease
is dopamine. It would be nice, perhaps, if we had something
that only affected dopamine, but that is not yet the case.
Tetrabenazine also reduced the amount of serotonin and
This lack of selectivity
can be expected to cause adverse effects. Indeed, persons who
take the drug can get depressed. Fortunately, there is some
indication that the depression caused by tetrabenazine can be
also has been investigated as a treatment
for tardive dyskinesia, and for
Tourette’s Syndrome. Preliminary results seem
promising. Xenazine is manufactured for the US market by Prestwick
A report about the
drug was prepared for the FDA by Prestwick; it is openly available vie
the FDA, here
(PDF). The gritty details about the pharmacokinetics and
pharmacodynamics start on page 17. The discussion of the
results of human testing start on page 30. The whole thing is
149 pages long.