Huntington's disease (HD) is an autosomal dominant disorder with a high penetrance
that leads to motoric and cognitive dysfunctions. It shows irregular, suddenly
occurring, uncoordinated movements of the distal extremities. In the early phase of
HD these movements appear only segmental or focal, in advanced stadium they include
more parts of the body. In addition, the patients develop dementia, behavioral and
psychiatric problems. Another complication is the weight loss despite an adequate
In most cases the first symptoms occur in mid-adult life (30 -50 years) and progress
over 10 to 15 years till death.|
HD is caused by an increase of the polyglutamine (CAG)-repeats in the Huntington
gene on chromosome 4. It is assumed that the mutated Huntingtin protein is toxic,
affecting among others the mitochondria in the central nervous system. On MRI
scans first impresses a progressing atrophy of the nucleus caudatus. Then in
later stages a diffuse cortical atrophy can be seen.
HD cannot be cured and a causal therapy does not exist. Therefore several
therapeutics are available for a symptomatic therapy.
For example, tetrabenazine inhibits the re-uptake of monoamines (dopamine, noradrenaline, serotonine)
into the presynaptic vesicle due to a blockade of the VMAT-2 transporter. Thus
higher amounts of monoamines are decomposed in the cytoplasm and existing
vesicles are evacuated. Together this leads to a presynaptic depletion of
monoamines. Furthermore an antagonist effect of tetrabenazine to the dopamine
D2 receptor is described, but the affinity is so low that no clinical consequence
can be seen.