Stanford study identifies molecular mechanism triggering Parkinson's Disease

7/28/2010

NPF's National Medical Director, Dr. Michael Okun, comments on Stanford University's study focused on the Parkinson's disease mutation. Read the full story from the San Jose Mercury News below.


Stanford study identifies molecular mechanism triggering Parkinson's Disease

Stanford scientists have identified a molecular pathway responsible for the death of key cells that causes Parkinson's disease, a discovery that could open the door to new treatments for the devastating malady.

A genetic mutation linked to the disease causes a malfunction in molecules called microRNAs, resulting in the overproduction of proteins that can cause brain cells to die.

"The clinical impact of our findings may be five to 10 years down the road," said pathology professor Bingwei Lu, senior author of the study published in today's issue of the journal Nature. "But their impact on our understanding of the disease process is immediate."

Parkinson's is a movement disorder characterized outwardly by tremors, difficulty in initiating movement and postural imbalance. In the brain, the disease leads to a massive loss of nerve cells in areas that fine-tune motor activity. It affects about 1 million people in the United States. The incidence of Parkinson's, rare in younger people, increases dramatically with age, although nobody is sure why.

"This study represents a truly new and potentially important piece of information for Parkinson's disease researchers," said Dr. Michael S. Okun of the University of Florida Movement Disorders Center in Gainesville, who is not affiliated with the team.

"The finding of a potential microRNA problem may help us to better understand specific mutations that may result directly, or indirectly, in the symptoms of Parkinson's disease," said Okun, a spokesman for the National Parkinson Foundation.

Working with fruit flies, the Stanford School of Medicine team studied a common mutation that's been implicated in many, although not all, cases of Parkinson's. This mutation, LRRK2, increases the likelihood of contracting the disease.

Fruit flies with the Parkinson's disease mutation were found to have faulty microRNAs, whose job it is to fine-tune protein production in cells. The result was death of cells that make the brain chemical dopamine — a hallmark of Parkinson's.

The mutated flies lost the dopamine-producing brain cells, so they couldn't move like normal flies. When tapped to the bottom of their plastic cage, normal flies quickly climb back up; the sick flies climbed up slowly, or simply sat at the bottom, said Lu.

Already, Lu's team has explored avenues of therapy. They found that reducing the levels of two overproduced proteins prevented the death of flies' nerve cells. Many pharmaceutical companies are already making compounds that act on these two proteins, which play roles in other diseases, as well.

"The flies no longer got symptoms of Parkinson's," said Lu. "This alone has immediate therapeutic implications."

This newly discovered link between the common Parkinson's-producing mutation and consequent microRNA malfunction is an exciting new finding — but its broader relevance must still be proven, said Okun.

"One issue moving forward," he said, "is how applicable this finding will be to all genetic and nongenetic causes of Parkinson's disease."

-- Lisa M. Krieger

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