May 10, 2023
The U.S. Department of Defense awarded Alison Axtman, Ph.D. in the UNC Eshelman School of Pharmacy’s Structural Genomics Consortium (SGC-UNC) a two-year grant totaling $1.5 million. The grant will go toward research that could one day lead to new medications and new treatment options for patients with Amyotrophic Lateral Sclerosis (ALS), or Lou Gehrig’s Disease.
ALS is a neurological disease that affects nerve cells in the brain and spinal cord that control voluntary muscle movement. Most cases are sporadic, meaning the disease seems to occur at random with no connection to family history or other risk factors.
Primary investigator Alison Axtman, Ph.D., research associate professor in the SGC-UNC, and co-investigator Adriana Beltran, Ph.D., associate professor at the UNC School of Medicine’s Department of Genetics, believe kinases represent a target class that can be modified using small molecules to develop new ALS drugs.
Kinases are an important class of proteins that are currently targeted by more than 70 small molecule FDA-approved drugs. More than 85% of these drugs have been designed for oncological indications. Despite this incredible drug development success and their playing essential roles in the brain, not a single kinase drug has been approved to treat a neurological disorder, such as ALS.
Because of the lack of focus on targeting kinases in the brain, the potential for these drugs to alter or halt neurological diseases has been left unknown. The buildup of a specific protein (TDP-43) in the brains of ALS patients, for example, is proposed to be regulated by a few kinases. This protein accumulates in patients that suffer from both inherited and sporadic ALS.
“We can use small molecules to specifically inhibit or degrade those kinases that enhance TDP-43 buildup, which will reduce or prevent this harmful process. Since protein buildup is common to nearly all individuals with the disease, our strategy is widely applicable and impacts nearly all ALS patients,” said Axtman.
The grant funding will support the training of a graduate student and allow the team to increase their research and development of these small molecules.
The small molecules could be developed into drugs and offer new treatment options to patients with ALS. These new drugs would not just address symptoms, like the currently available FDA-approved ALS drugs. Instead, these drugs would eliminate protein aggregation, which is one major cause of patient decline in ALS, and they have the potential to slow or halt disease progression.
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