Asim Beg, assistant professor at University of Michigan in Ann Arbor, was awarded an MDA research grant totaling $300,000 over a period of three years to study the role of a protein, EphA4, in amyotrophic lateral sclerosis (ALS). High levels of EphA4 correlate with rapid disease progression in ALS patients. Beg and colleagues will work on the development of a strategy to reduce EphA4 levels. This work will provide insight into the molecular mechanisms of motor neuron degeneration and will facilitate new strategies to slow ALS disease onset and progression.
Please describe your current research.
Mutations in the repulsive axon guidance receptor EphA4, a known human ALS modifier, delay disease onset and prolong survival in human ALS patients. Moreover, numerous ALS-associated mutations converge to alter actin cytoskeletal dynamics, implicating that disruption of cytoskeletal architecture may be a central mechanism underlying ALS pathogenesis. However, the critical signaling proteins that drive pathological cytoskeletal alterations are largely unknown.
We have identified a protein that links repulsive EphA4 signaling to actin cytoskeletal reorganization, which when inhibited delays disease onset, suppresses motor neuron degeneration and significantly extends lifespan in ALS mouse models. Our results will provide important insight into the molecular mechanisms of motor neuron degeneration and will facilitate new strategies to slow ALS disease onset and progression.
What inspired you to study ALS?
The devastating impact that ALS has on patients and their families is a major factor that has inspired me to study the disease. The lack of therapies to delay disease onset or progression is a major roadblock. Thus, identifying strategies that alter disease trajectory to regain quality of life would be incredibly beneficial for both patients and families.
What is your area of focus within the ALS field and why is it important?
My focus is to identify key convergent signaling pathways that are altered in ALS motor neurons that drive neurodegeneration.
Understanding the key critical intersecting pathways involved in motor neuron degeneration is a logical path to identifying new therapeutic strategies to halt or delay motor neuron degeneration.
Why is it important that MDA continue to fund research in ALS?
The impact that ALS has on patients and their families is devastating. Identifying strategies that can delay the progression and onset of the disease will have the broadest impact and improve quality of life for those affected.
What do you feel people impacted by ALS can have the most hope about with respect to research right now?
The massive amount of information and identification of genetic risk factors and signaling pathways involved in the disease pathogenesis provides a promising foundation for creating new strategies to treat the disease.
Does your work have any potential implications for other disease fields?
Motor neuron degeneration is the unifying feature in ALS, spinal muscular atrophy (SMA), Parkinson’s, Alzheimer’s and Huntington’s disease; therefore, our findings may provide a shared strategy to protect motor neurons from degeneration in these other devastating disorders.