Published On: Thu, Sep 27th, 2012

Huntington's Disease and Drugs for its Treatment

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What is Huntington’s Disease?

Huntington’s disease is a kind of neurodegenerative disorder, which is an inherited (autosomal dominant) disorder.

What does Huntington’s disease result in?

It results in progressive brain degeneration, which starts in adulthood and cause rapid deterioration and death. It also causes dementia and severe motor symptoms like involuntary writhing movements (twistings/contortions), which are disabling movements.

It is the commonest of the trinucleotide repeat neurodegenerative diseases. It is associated with the expansion of the number of repeats of the CAG sequence in the specific genes and the number of consecutive glutamine residues in the expressed proteins.

When do symptoms appear and a note on Huntingtin protein?

The larger the number of repeats, the earlier the appearance of the symptoms. Huntingtin is the protein that is coded by the gene of the Huntington’s disease. This protein interacts with various regulatory proteins, including one of the caspases, which participates in excitotoxicity and . Some of these interactions are enhanced by the poly-Gln repeat in the mutant protein, which accounts for the neuronal loss, affecting mainly the cortex and the striatum, resulting in the progressive loss of memory (dementia) and severe involuntary jerky movements.

The mutant protein may also be prone to misfolding and aggregation. The studies on post-mortem brains have showed that there was a 75% reduction in the activity of the glutamic acid decarboxylase, the enzyme that is responsible for the GABA synthesis and the dopamine content of the striatum was normal or slightly increased.

The loss of GABA-mediated inhibition in the basal ganglia produces a hyperactivity of the dopaminergic synapses and it shows some senses as a mirror image to the Parkinson’s disease.

The effects of that influence the dopaminergic transmission are opposite of the effects of drugs that are used in the Parkinson’s disease.

Drugs used for the treatment of Huntington’s Disease:

Dopamine antagonists are effective in reducing the involuntary movements. The drugs like Levodopa and Bromocriptine worsen the involuntary movements. The drugs that alleviate the motor symptoms include dopamine antagonists like chlorpromazine and the GABA agonist baclofen. These drugs do not affect the dementia or retard the course of the disease. The drugs act by inhibiting the excitotoxicity or neural transplantation procedures may be useful, which are still under the experimental phase.

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