Neuron-loving protein could treat Parkinson's

By Mike Nagle



Amgen
neurotrophic
Parkinson's
CDNF
Third time lucky for Parkinson's drugs?


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05/07/2007 - The discovery of a new protein that can protect, and even rescue, damaged dopamine neurons could significantly impact future Parkinson's therapies.

As revealed in today's issue of Nature, scientists at the University of Helsinki, Finland, have discovered a new protein called conserved dopamine neurotrophic factor (CDNF), which could form the basis for a new drug to tackle the debilitating effects of Parkinsons.

Around one per cent of people over 60 get the disease and the aging global population means this figure is set to rise. It causes dopamine-producing nerve cells in the brain to die, leading to muscle rigidity and slowness of movement.

The current gold-standard of therapy is levodopa (L-dopa), which replaces the lost dopamine. However, this drug becomes less effective over time and the increasing doses cause side effects such as uncontrollable movement.

Therefore, drugs that could slow or halt the progression of the disease are badly needed. In fact, this is not the first time that neurotrophic proteins have been investigated as a possible answer. Amgen was looking at glial cell-line derived neurotrophic factor (GDNF), which did indeed show positive effects in clinical trials. However, development was halted in 2005 with Amgen citing adverse effects as the reason.

At the time, the Amgen CEO, Kevin Sharer, said: "We've looked at this decision from every perspective -- scientific, medical and ethical. Our hearts truly go out to trial patients and their families, but we simply cannot allow trials to continue given the potential safety risks and the absence of proven benefit."

Since then, others have been searching for similar proteins to GDNF but ones that will be better tolerated.

When the CDNF was tested by Professor Raimo Tuominen in an experimental model of the disease, the researchers found that dopamine neurons were protected and even recovered - even after an experimental lesion of neurons in the area of the brain that causes Parkinson's (the Substantia Nigra).

The scientists injected one side of a rat's brain with 6-OHDA to cause the dopamine nerves to progressively degenerate. A single injection of CDNF six hours before delivery of the toxin "significantly prevented the degeneration of dopamine nerves in the brain" and the rat's movement returned to normal.

If the CDNF was given four weeks after the toxin instead, it still prevented nerve degeneration and cured the behavioural imbalance.

CDNF belongs to a family of molecules that is the first evolutionarily conserved family of neurotrophic factors having a representative also in invertebrate animals.

Ceregene is actively investigating this family of proteins also. Its Cere-120 gene therapy is based upon the gene for neurturin, a member of the GDNF family. Just over a week ago, Genzyme committed well over $150m (€112m) to its development.

http://www.biopharma-reporter.com/news/ng.asp?n=77964-university-of-helsinki-amgen-neurotrophic-parkinson-s-cdnf-gdnf