Grant: Operating Grant - Priority Announcement: Neuromuscular Research

Lou Gehrig's disease, also known as amyotrophic lateral sclerosis or ALS, is a disease that causes the death of nerve cells in the brain and spinal cord. The disease specifically targets the motor neurons that are essential for producing movement. Individuals with the disease become progressively weaker until fully paralyzed and die within 3-5 years of diagnosis. While motor neurons are particularly susceptible to ALS, we recently found that motor neurons connected to fast twitch muscle are especially vulnerable whereas motor neurons connected to slow twitch muscle show some resistance to the disease. We have used three types of interventions to convert fast into slow twitch muscle and have preliminary evidence that all three enhance the survival of motor neurons. We think it is likely that the molecular mechanisms that result in protecting the motor neurons are common for the three interventions. We will test this hypothesis by measuring changes in gene expression that are common across the three interventions. These results will identify which genes and proteins are ultimately responsible for the protective effect that results when the fast twitch muscles are converted to slow. These results will be translated into specific exercise training recommendations for people with ALS and will aid in the development of evidence based treatments for this devastating disease.