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Home » ALS Drug Grant to Spur Drug Discovery at Northwestern
Disease Discoveries

ALS Drug Grant to Spur Drug Discovery at Northwestern

By Marla PaulSep 5, 2019
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Promising early results of compounds to address protein clumping and neuron degeneration

P. Hande Ozdinler, PhD, associate professor of  Neurology in the Division of Neuromuscular Disease, and Richard Silverman, PhD, the Patrick G. Ryan/Aon Professor in the departments of chemistry and molecular biosciences in the Weinberg College of Arts and Sciences, will lead the drug discovery project.

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

The grant was awarded to P. Hande Ozdinler, PhD, Associate Professor of  Neurology in the Division of Neuromuscular Disease, and Richard Silverman, PhD, the Patrick G. Ryan/Aon Professor in the departments of chemistry and molecular biosciences in the Weinberg College of Arts and 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. “

Silverman is a member of the Chemistry of Life Processes Institute, Center for Molecular Innovation and Drug Discovery and Center for Developmental Therapeutics. Ozdinler is a member of Les Turner ALS Center, Mesulam Center for Cognitive Neurology and Alzheimer’s Disease and the Robert H. Lurie Comprehensive Cancer Research Center of Northwestern University.

The NIH grant is 1 R01 AG061708-01A1from the National Institutes of Health.

The initial phases of research were supported by the Les Turner ALS Foundation and an N.XT grant.

Neurology and Neuroscience Research
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