Huntington's disease is named after a 19th century New York neurologist who studied several families who suffered from a severe, and lethal, motor disorder which appeared to be inherited as an autosomal dominant gene. It was calculated that 50% of the offspring of an affected person have a probability of contracting the disease. The frequency in the general population is 0.01%.
Symptomatically, Huntington's disease is characterized by dyskinesias (choreoform movements) which start with the fingers and then spread to the rest of the body. Akinesia also occurs as a result of the basal ganglia dysfunction. However, unlike most types of Parkinson's disease, Huntington's disease develops during early middle age (30-40 years), it is progressive and results in death in approximately 20 years from the start of the symptoms. In the final years of the disease, the patient suffers severe motor impairment, emotional lability and dementia.
The main neurochemical deficit occurs in the GABA/enkephalin neurons in the striatum, particularly in the neurons that project to the external globus pallidus which forms part of the indirect striatal pathway. As a consequence, the direct pathway, in which the GABA/dynorphin-contain-ing neurons predominate, becomes dominant which provides the neurochemical basis for the dyskinesia. Thus, unlike Parkinson's disease, there is no loss of dopaminergic neurons but a primary deficit in GABA, the opioid peptide and substance P. So far, it has not been possible to counteract the symptoms by replacing the defective neurotransmitters. In the early stages of the disease in which the dyskinesia predominates, antipsychotic drugs blocking the D2 receptors may offer some relief by reducing the inhibitory input to the GABA/enkephalin neurons and thereby help to restore the balance between the direct and indirect pathways. However, such treatments are usually only marginally effective and there is a possibility that akinesia may be precipitated. Despite some interesting observations in the transgenic mouse model of Huntington's disease, in which such a diverse group of drugs as creatine, monocycline, remacemide (a glutamate antagonist) and co-enzyme Q were shown to slow the symptoms of the disorder, there is no evidence that they are effective in patients.
With regard to the pathological basis of Huntington's disease, research has been focused on the role of the mutant huntingtin protein. Huntingtin is associated with the cytoskeleton and the intracellular vesicles; it is enriched in the striatum. While the precise role of the mutant protein is uncertain, it has been hypothesized that it plays a role in the transcription and regulation of other proteins, abnormal transcription thereby resulting in premature apoptosis. Hopefully recent research into the transgenic mouse model, and the effects of subchronic interleukin-1 in the rat, may enable a better understanding of the pathology of the disorder to be obtained. It is not without interest that the polyunsaturated fatty acid eicosapentaenoic acid has been shown to attenuate the symptoms of the disorder not only in the animal models but also in patients. This finding, if replicated in controlled trials, could provide a new insight into the cause, and treatment, of Huntington's disease.
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