Amyotrophic lateral sclerosis (ALS), known commonly as Lou Gehrig’s disease in the United States, is an adult-onset neurodegenerative disorder that is usually fatal within three to five years of the initial presentation of symptoms. The disease is characterized by the progressive loss of the motor nervous system and voluntary muscle function. To date, there is no effective means to slow or reverse the progression of ALS. Thus, my laboratory seeks to provide information which will translate to both improving the general health and extending the lives of ALS patients.
While motor neuron death is perhaps the most recognized characteristic of ALS, the molecular events that underlie ALS are not restricted to the nervous system. A more accurate description of ALS pathology is that paralysis occurs as a result of motor unit loss. In this regard, the fidelity of these connections between motor neurons and skeletal muscle is dependent not only on neuronal input but also on the integrity of the muscle. For this reason, we endeavor to reveal a link between impaired intrinsic muscle excitability and the loss of motor units in ALS. To establish such a connection, my laboratory will utilize a combination of biochemical, electrophysiological, optical and calcium imaging techniques. Looking forward, we aim to identify small molecules as therapeutic targets in the fight against ALS and other degenerative neuromuscular diseases.