Grant: Project Grant

Amyotrophic lateral sclerosis (ALS), commonly known as Lou Gehrig's disease, is a devastating disease marked by the deterioration of nerve cells that control muscles, leading to paralysis and ultimately death. ALS afflicts approximately 30,000 people in North America; however, there is currently no cure for this disease. ALS can be genetically inherited or can occur sporadically in people without any apparent history of the disorder in their family. The cause(s) of sporadic ALS remain(s) unknown. Infection with enteroviruses, a family of RNA viruses that include poliovirus, coxsackievirus, enterovirus-A71, and enterovirus-D68, has been proposed as a possible factor because they can target muscle-controlling nerve cells and polio survivors have been reported to experience new weakening in muscles that were previously affected by viral infection. However, definitive evidence of the role of enteroviruses in sporadic ALS is lacking. We recently made an exciting discovery that enteroviral infection results in the hallmark molecular and pathological features of ALS. In the present project, we will examine whether enteroviral infection induces ALS-like symptoms in normal mice and/or accelerates disease onset and progression in mice that are genetically susceptible. We will also test whether application of anti-enterovirus drugs can lessen the development of ALS. Moreover, we will investigate the possible mechanisms involved, with an emphasis on the RNA metabolic pathway, the host disposal system for damaged proteins and organelles, and the spreading mechanisms of ALS. We expect that the results of this project will not only uncover a potentially powerful new factor that contributes to the development of ALS, but also will allow for the development of novel forms of treatments for ALS.