Worm model could yield new Parkinson’s drugs

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The Michael J. Fox Foundation for Parkinson's Research has awarded one of its competitive Fast Track grants to Vanderbilt neuroscientist Richard Nass, Ph.D., to fund his search for drugs that will prevent dopamine nerve cell death. The Foundation's annual Fast Track awards aim to stimulate innovative and high impact Parkinson's research.

Nass's plan is certainly novel — his drug search will involve millions of microscopic worms. Though worms are not known to get Parkinson's disease, they do have dopamine neurons, the same type of nerve cells that die in humans suffering from Parkinson's disease.

Dopamine neurons populate regions of the human brain responsible for movement. The death of these neurons leaves Parkinson's patients with shaking limbs, uncoordinated movements, and shuffling gaits. No one knows why these neurons die.

"If we can find drugs that prevent the death of dopamine neurons in worms, they could be good candidates for protecting human dopamine neurons as well," said Nass, research assistant professor of Pharmacology.

Why the worm? Scientists have increasingly turned to the tiny roundworm, named C. elegans, as a model for human diseases. The worm's short lifespan, small size, and transparent body make it ideal for laboratory study. And at the molecular level, the worm's nervous system is very similar to the human nervous system, Nass said. "It is a very powerful model organism."

Nass and colleagues, including Randy Blakely, Ph.D., director of Vanderbilt's Center for Molecular Neuroscience, discovered a way to make the worm's dopamine neurons — all eight of them — "glow" green, allowing the scientists to actually look at the neurons in living worms.

"It was the first time that anyone's ever been able to clearly see all the dopamine neurons in a living animal," Nass said. What's more, the investigators found they can selectively kill the dopamine neurons by exposing the worms to neurotoxins that are known to induce Parkinson's symptoms in mammals. As the dopamine neurons die, their green glow dims and then disappears entirely.

This simple visual outcome offers a unique tool for drug screening, Nass said. If a drug protects the dopamine neurons against toxin-induced death, the green lights will continue to shine.

Nass will collaborate with industry partner Cambria Biosciences to develop and implement high-throughput screening methods that will be used to assess many different drug candidates. Cambria Biosciences is a drug discovery company dedicated to finding the next generation of medicines for treating neurological diseases.

"The compounds that we find to be neuroprotective will provide good leads for new Parkinson's disease drugs," Nass said.