The Corpus Callosum

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
.   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,
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.  

People who
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
treated effectively

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
Pharmaceuticals, Inc

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.


  1. #1 Doubting Foo
    August 18, 2008

    I know someone who has a friend with Huntington’s but didn’t know it until AFTER he fathered two sons. But he hasn’t told them and as far as I know doesn’t plan to. I don’t understand his reasoning…

  2. #2 stumpy
    August 18, 2008

    I appreciate the posting, and also the comment by Doubting Foo. The ethics of Huntington’s are, to me, more interesting than the pathophysiology. Should the friend w/ HD inform his sons? My answer is, “probably yes” — using the “greatest good for the greatest number” test, it seems that he should certainly do so before they in turn sire children. So: Why does he not do so? To answer this, try to put yourself in his place, and think about his position: Surely one of the worst situational set pieces that modern medical genetics can contrive. And then try to think about it with a mind that — as the friend’s mind might be — is ravaged by HD. I realize that this is impossible. You might as well try to regard reality thru the lens of a delirium. But your friend may already be having difficulty reasoning, as a result of his own HD… Complicating things much further.

  3. #3 Amiya Sarkar
    August 26, 2008

    That FDA finally woke up to the reality of its ethical moratorium, is surely encouraging. It was very prompt in granting sildenafil (viagra) its seal of approval. Perhaps we need to think about GABA neuronal transmission too, for the search of an effective cure.

  4. #4 Newell D Anderson
    June 7, 2009

    Your article on Tetrabenazine is most appreciated by us “civilians”. My mother-in-law died of complecations of HD some 20+ years ago, I have 2 brothers-in-law that have very different forms of the disease, both from each-other, & from there mother. My wife now has a totally different version. Through all of that time, I never heard of Tetrabenazine, until last week! I assure you, if we had heard, we would have had a new Mexico-US drug cartel.
    The biggest problem with treating HD, from our standpoint is finding a Doctor that knows what it is. At this moment one of the largests hospitals in Houston, TX want to put my wife on a Phyco-ward instead of neurology, to treat HD!

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