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Science in mind

New experiments targeting Parkinson’s

Susan Lindquist

Susan Lindquist

A team of scientists at the Cambridge-based Whitehead Institute for Biomedical Research have identified a compound that can reverse some of the toxicity that occurs in brain cells created from Parkinson’s disease patients’ stem cells.

The work, described in a pair of studies published Thursday in the journal Science, is still very early — the researchers aren’t even using the word “drug” when describing the small molecule that jumped out when they screened a chemical library of about 200,000 compounds. But the methods they used demonstrate the power of an approach that knits together multiple basic biology technologies.

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Similar experiments may now be used to aid drug development efforts in a wide variety of neurodegenerative diseases, including ALS (Lou Gehrig’s disease) and Alzheimer’s.

“It’s a very nice piece of work — an elegant demonstration of bridging basic yeast screens to cells that are directly relevant to the human condition,” said Dr. Dennis Selkoe, professor of neurologic diseases at Brigham and Women’s Hospital and Harvard Medical School, who was not involved in the studies. “The drug in question did interesting things, but is still a long way from being converted into a medicine that people can take.”

The work in Susan Lindquist’s laboratory at the Whitehead grew out of her ongoing efforts to utilize the humble Baker’s yeast to model complex neurodegenerative diseases. The researchers engineered the yeast to overproduce alpha-synuclein, a protein that forms toxic clumps in the brains of Parkinson’s patients.

Similar to human brain cells, yeast were sickened when the protein formed clusters. The researchers then looked for compounds that were able to reverse the problems. A few seemed promising, but one in particular appeared to affect the way the cells cleared out the alpha-synuclein clusters.

Researchers collected cells from patients with an aggressive, genetic form of Parkinson’s samples and used a technique that won the Nobel prize in 2012 to create stem cells. From the stem cells, they created the neurons that are afflicted in Parkinson’s and tested the compound, finding it could reverse signs of pathology.

Carolyn Y. Johnson can be reached at cjohnson@globe.com. Follow her on Twitter @carolynyjohnson.
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