Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig’s disease, is a progressive, neurodegenerative disorder characterized by the progressive loss of motor neurons controlling voluntary muscles and leading to paralysis. In addition, spinal interneurons and descending motor system (corticospinal and rubrospinal tract) show extensive degeneration. The accumulation of a misfolded protein in alpha motor neurons (but also in glial cells) gradually reduces function, eventually causing affected cells to atrophy and die. Until now, there has been no treatment to halt disease progression. Some familial form amyotrophic lateral sclerosis (FALS) has been linked to mutations in the homodimeric enzyme Cu/Zn superoxide dismutase 1 (SOD1) resulting in progressive motor neuron and descending motor tracts death through one or more acquired toxicities.
Our research study aims:
- to understand the molecular mechanism of SOD1 gene-mutation-linked ALS,
- to develop and characterize a new subpial route for spinal delivery of AAV9 encoding an shRNA-SOD1, and,
- to test the treatment potency of subpially-delivered shRNA-SOD1 in suppressing the disease onset/progression in SOD1-gene mutation transgenic rodent models of ALS (G93A, G37R)
Extensive A-motoneuron and interneuron degeneration in end-stage G37R ALS mice (compare to wild-type age-matched animal)