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Grant Fuels Drug Discovery Efforts for ALS

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Two Northwestern University scientists have received a $3.1 million grant from the National Institute on Aging (NIA) to collaborate and investigate drug therapies for amyotrophic lateral sclerosis (ALS).

The grant was awarded to P. Hande Ozdinler, associate professor of neurology at Northwestern University Feinberg School of Medicine, and Richard B. Silverman, the Patrick G. Ryan/Aon Professor in the departments of chemistry and molecular biosciences in the Weinberg College of Arts & Sciences.

ALS, also known as Lou Gehrig's disease, is a progressive neurodegenerative disease that affects nerve cells in the brain and spinal cord. There is an immense global effort to identify effective treatments.

Silverman, the inventor of Lyrica, previously received a U.S. Department of Defense grant to screen compounds that overcome protein aggregation and then modify them for enhanced potency. Protein aggregation -- when nerve cell proteins accumulate and clump together -- is often correlated with such neurodegenerative diseases as ALS, Alzheimer's and Parkinson's.

"The problem we are trying to solve is to identify a common underlying cause for many different neurodegenerative diseases," Silverman said. "The compounds we develop initially for ALS may have broader applications for neurodegeneration."

Silverman and Ozdinler began to collaborate to investigate whether these compounds and their derivatives would have an impact on the degenerating upper motor neurons in ALS. Ozdinler's previous research showed that degeneration of the upper motor neurons, not just spinal neurons, is an important contributor to ALS.

"Our initial results with these compounds are quite promising, and because we use upper motor neurons, our findings will have implications in other upper motor neuron diseases as well," Ozdinler said.

Ozdinler is able to cloak the upper motor neurons that die in ALS in green fluorescence.

"We can now track their responses to compounds both in a dish and in the brain," Ozdinler said. "This was not possible in the drug discovery field before. "

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