New Scientist : Parkinson's drug prompts brain cell growth
http://www.newscientist.com/article.ns?id=dn7619

Parkinson's drug prompts brain cell growth
16:55 01 July 2005
NewScientist.com news service

by Rowan Hooper

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controversially withdrawn over toxicity fears – has now been shown to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)

 The full journal article is at:
Glial cell line-derived neurotrophic factor induces neuronal sprouting in
human brain by
Seth Love1, Puneet Plaha2, Nikunj K Patel2, Gary R Hotton3, David J
Brooks3 & Steven S Gill2
 Nature Medicine, July 1, 2005.
http://www.nature.com/nm/journal/v11/n7/full/nm0705-703.html

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