Defense Department Awards ALS Drug Development Grant to Miller School Researchers

A new drug development grant from the U.S. Department of Defense will allow researchers at the University of Miami Miller School of Medicine to study potential treatments for amyotrophic lateral sclerosis (ALS), a neurological degenerative condition commonly called Lou Gehrig’s disease.

“Despite decades of research and dozens of clinical trials, ALS remains an incurable disease,” said Claes Wahlestedt, M.D., Ph.D., Vice Chair for Research, Leonard M. Miller Professor of Psychiatry and Behavioral Sciences, Associate Dean for Therapeutic Innovation, and Director of the Center for Therapeutic Innovation. “Currently, the median interval from the onset of symptoms to death is three years, and the only drug with a beneficial effect is Riluzole, which only prolongs survival by several months.”

The Department of Defense (DOD), which has a long relationship with the Miller School, recently awarded the $600,000 grant to co-principal investigators Wahlestedt, Michael Benatar, M.D., Ph.D., associate professor of neurology and Chief of the Neuromuscular Division, and Zane Zeier, Ph.D., assistant scientist in psychiatry and behavioral sciences. Although about 100 institutions applied for the DOD “therapeutic idea” grant, the Miller School application was the only one funded, said Benatar, adding that a pilot grant from the ALS Association helped the researchers prepare the groundwork for the two-year DOD-funded study. UHealth offers a multi-disciplinary ALS program for patients.

The Miller School researchers will study a wide range of compounds that could be used to develop drugs to treat patients with a recently discovered genetic mutation that is related to some types of ALS and to frontotemporal dementia (FTD). “Our therapeutic approach is based on a well-defined hypothesis of how this mutation causes neuron degeneration in about 10 to 15 percent of ALS patients,” said Benatar. “Since the same mutation also occurs in patients with FTD, they are also highly likely to benefit from any new drugs.”

Benatar said the researchers will take a parallel drug development strategy using advanced biological assay technology to accelerate the search for potential treatments. First, the team will screen existing compounds that have received approval from the Food and Drug Administration (FDA) for another purpose to see if they are also effective against neuron degeneration. “If an FDA-approved compound appears to show promise, then the pathway to clinical trials can be swift,” Benatar said. At the same time, the researchers will be screening new compounds for effectiveness. Since more data will be needed to determine the safety and effectiveness of those compounds, it will take longer to bring them from the laboratory into clinical trials.

“The tool we have developed to facilitate our therapeutic discovery efforts is called a semi-high-throughput screen,” said Zeier. “That enables us to rapidly evaluate a large number of potential therapeutic compounds within a relatively short period of time. Once we identify compounds that appear to have a therapeutic effect, we will validate them using more specific laboratory tests.”

About 6,000 people are diagnosed with ALS each year, and 20,000 to 30,000 people are living with the disease in the U.S. Early symptoms often include muscle weakness in the arms and legs and difficulties with speech, swallowing or breathing. As neurons that control the body’s motor movements die, patients in the later stages of the disease may become paralyzed. ALS primarily affects adults in their 40s to 70s.

“We used to think of ALS as a specific disease with minimal contribution from genetic risk factors,” Benatar said. “But genetic researchers have now identified more than 20 different genetic causes. Therefore, a single treatment may not be effective for all patients with ALS, and targeted treatments may be needed for individual patients with various forms of the disease.”

Other Miller School collaborators in the project are Stephan Züchner, M.D., Ph.D., professor and interim chair of the Dr. John T. Macdonald Foundation Department of Human Genetics and Neurology Director of the Center for Human Molecular Genomics at the John P. Hussman Institute for Human Genomics, and Joanne Wuu, Sc.M., research assistant professor of neurology. Since 2001, the Miller School has received approximately $48 million in cumulative research funding from the Department of Defense.

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