Grant: Operating Grant

It is estimated that 2 out of 100,000 people will be diagnosed each year with the degenerative motor neuron disease, amyotrophic lateral sclerosis (ALS). Patients suffering from ALS face a severely impaired quality of life and a rapid degeneration causing death. An important part of ALS research involves investigations into why motor neurons are selectively lost in this disease, and how they might be replaced in order to restore the functions of sufferers. In this regard, understanding how motor neurons are generated and become part of neural circuits controlling motor functions is of utmost importance for the development of successful strategies of neuron replacement therapy for ALS and other motor neuron diseases. The present application seeks to characterize the mechanisms that govern the development and connectivity of selected motor neurons known to be vulnerable to degeneration in ALS in order to use this information to develop motor neuron replacement therapies. More specifically, it is proposed to investigate how motor neurons that control muscles involved in voluntary movement and breathing acquire their specific cellular properties and become connected to their target muscles. It is then proposed to use this information to develop strategies to promote the regeneration of these particular classes of motor neurons from pluripotent embryonic stem cells. The results of the planned investigations will provide new insight into how to promote the regeneration of particular types of motor neurons with defined characteristics. Restoring muscle functions through the production of new motor neurons from either endogenous or transplanted stem/progenitor cells represents one of the highest priorities in the treatment of many neurodegenerative diseases, including ALS.