Promising New Drug Targets Identified for Huntington's Disease

by VR Sreeraman on  March 24, 2008 at 12:59 PM Research News
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Promising New Drug Targets Identified for Huntington's Disease
A new study conducted by researchers at the University of Cambridge has provided a number of promising new drug targets for Huntington's disease, a neurodegenerative disease.

They have identified a number of candidate drugs to study further as to which encourage cells to eat the malformed proteins that causes the disease.

Huntington's disease is marked by build up of malformed proteins in brain cells, mainly in the basal ganglia and the cerebral cortex.

Generally, cells dispose of or recycle their waste material, including unwanted or misfolded proteins, through a process known as autophagy, or 'self-eating'.

And Professor David Rubinsztein, a Wellcome Trust Senior Clinical Fellow at the University of Cambridge, along with his team has already shown that stimulating autophagy in the cells could be an effective way of preventing the malformed proteins from building up.

Now, the same researchers have shown that a number of FDA-approved drugs for treatments such as migraine and hypertension are able to stimulate autophagy in fruit flies and zebrafish through unexpected pathways.

"By screening a number of drugs that have already been shown to be safe in humans, we have been able to identify some unexpected and very promising pathways involved in Huntington's," Nature quoted Professor Rubinsztein, as saying.

Verapamil, which is currently used to treat high blood pressure and heart arrhythmias, is one of the drugs tested that inhibits the influx of calcium into cells, which, in turn, appears to regulate autophagy.

Likewise, clonidine, which is currently used to treat hypertension or migraine, appears to work on autophagy by decreasing levels of cAMP, a molecule that is important in many biological processes.

The researchers said that if the drugs can stimulate autophagy effectively over long-term periods in human brains, then they might have the potential to help delay the onset of Huntington's disease.

The candidate drugs are comparatively safe and well tolerated when used to treat the diseases they were designed for.

A minimal side-effect profile would be highly desirable for a drug treatment aiming to delay the onset or slow the progress of Huntington's disease.

Such drugs may need to be taken for decades, and even moderate side effects may discourage people from taking them over a long period.

"If we can find a safe, well tolerated drug, then a person at risk could be placed on a drug regime to help prevent onset. It is much easier to stop something happening than having to treat it once it has started," Rubinsztein

The researchers will soon start testing the drugs in other animal models to evaluate their safety and efficacy.

The study is published online in the journal Nature Chemical Biology.

Source: ANI

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