Grant: Operating Grant - Priority Announcement: Neuromuscular Research

Amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease, is an insidious and rapidly progressing disease affecting the brain, spinal cord and muscle function. ALS is a disease of motor neurons, which are specialized cells needed for muscle control. Diagnostic features of the disease are muscle weakness and paralysis, with an invariably fatal outcome. The swiftness of the disease progression makes ALS devastating for the affected individuals as well as their loved ones. Much progress has been made in understanding the disease mechanisms underlying the inherited form of ALS with the aid of an excellent mouse model. Mounting evidence from numerous studies suggests that ALS is actually a multi-systemic disorder, and disease progression is influenced by cells other than motor neurons. A recent study suggests that muscle is also a primary target organ affected in the familial form of ALS. In our preliminary study, specific genes expressed in muscle alone significantly modulated disease onset and progression in an ALS mouse model expressing a human ALS gene (the mutant G93A human SOD1 gene). The proposed studies aim to determine the skeletal muscle properties important for modulating ALS disease progression. These studies may lead to the development of effective muscle-based therapies for ALS.