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Parkinson's Drug Prompts Brain Cell Growth

A drug that relieves the symptoms of Parkinson's disease - but was controversially withdrawn over toxicity fears - has now been shown to stimulate growth of the nerve fibres damaged by the disease.

When delivered directly to the brain, glial cell-line derived neurotrophic factor (GDNF) had been shown to stimulate regrowth of cells in animal models of Parkinson's. But this is the first time regrowth has been seen in the human brain, says Steven Gill, a neurosurgeon at Frenchay Hospital, Bristol, UK.

Gill was running a trial study where five patients with advanced Parkinson's disease were fitted with a tiny catheter that delivered GDNF direct to the putamen, part of the basal ganglia in the centre of the brain. In the putamen of Parkinson's patients the chemical messenger dopamine is lost.

The symptoms of Parkinson's - which include uncontrollable shaking and trembling - were reduced in all five patients. They showed dramatic improvements with respect to their motor skills, verbal memory, facial expressions and motivation.

Frustrating situation

However, Amgen, the company that makes GDNF, withdrew the drug after fears over its toxicity and a second trial of 34 patients was halted. That was despite the fact that the toxicity trials involved testing far higher doses of GDNF on animal models, and that none of the human subjects had showed any ill-effects.

"For people with Parkinson's disease the situation is frustrating when we've seen significant benefits of GDNF," says Gill. In the US, some patients involved in halted clinical trials are taking legal action to try to force Amgen to supply them with the drug.

Gill, Seth Love, and colleagues were able to demonstrate the regrowth of cells in the human brain after a patient in the original GDNF trial later died of a heart attack. Examination of his brain showed that nerve fibres in the putamen had "sprouted" - specifically in the substantia nigra region where the cells that produce dopamine are sited.

This patient had suffered from unilateral Parkinson's disease, where only half the brain is affected. Therefore a catheter had been fitted only to that half of the brain, enabling the researchers to demonstrate that nerves had sprouted only in the area treated with GDNF.

Journal reference: Nature Medicine (DOI: 10.1038/nm0705-703)

Source Date: Jul 01 2005
Source Publication: New Scientist
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