Introduction
Huntington disease is an autosomal dominant disorder characterized by chorea, neuropsychiatric symptoms, and progressive cognitive deterioration, usually beginning during middle age. It is a fatal neurodegenerative disorder and together with spinobulbar muscular atrophy (SBMA), dentatorubral pallidoluysian atrophy (DRPLA), and spinocerebellar ataxia (SCA) types, 1, 2, 3, 6, 7, and 17 known as a polyglutamine (polyQ) disease.
Huntington Disease typically begins in midlife (but there is juvenile onset) and is characterised by progressive neuronal dysfunction and neuronal loss, and patients die 10 to 15 years after the onset of symptoms. The selective neurodegeneration in the brain occurs most prominently in the striatum and deep layers of the cerebral cortex. In advanced stages of the disease other brain regions such as the hippocampus, hypothalamus, cerebellum and amygdala can also be affected.
Huntington disease results from a mutation in the huntingtin (HTT) gene (on chromosome 4), causing abnormal repetition of the DNA sequence CAG, which codes for the amino acid glutamine. The resulting gene product, a large protein called huntingtin, has an expanded stretch of polyglutamine residues, which accumulate within neurons and lead to disease via unknown mechanisms. The more CAG repeats, the earlier the onset of disease and the more severe its expression (phenotype). The number of repeats can increase with successive generations and, over time, lead to increasingly severe phenotypes within a family (called anticipation).
Pharmacological Intervention
Pharmacological interventions typically address the hyperkinetic movement disorders that may be associated with Huntington Disease, such as chorea, dystonia, ballism, myoclonus, and tics.
An American Academy of Neurology Guidelines recommended the use of:
- tetrabenazine (TBZ),
- amantadine, or
- riluzole in the treatment of chorea.
Other medications that are commonly considered when treating chorea include:
- dopamine antagonists
- benzodiazepines, and
- glutamate antagonists.
Dopamine antagonists (neuroleptics) are perhaps the most commonly considered agents in the management of chorea and psychosis in patients with HD, but there are few evidence on its efficacy and safety.
Olanzepine, Quetiapine, Clozapine and aripiprazole are some neuroleptic that have been evaluated for management of chorea in Huntington Disease, they showed beneficial effects with tolerable side effects.
Riluzole also reduces chorea by retarding striatal glutamate release