ALS (SOD1)

AMT-162 is designed to be a novel, one-time, intrathecally administered gene therapy for ALS caused by mutations in SOD1, a rapidly progressing, rare motor neuron disease that leads to loss of everyday functions and is uniformly fatal.

Mutations in the SOD1 gene of ALS account for approximately one-fifth of all inherited forms of this fatal disease. AMT-162 is comprised of a recombinant AAVrh10 vector that expresses a micro ribonucleic acid (miRNA) designed to knock down the expression of SOD1 with the goal of slowing down or potentially reversing the progression of ALS in patients with SOD1 mutations.

The clinical development of AMT-162 is based on nearly 30 years of research demonstrating the link between the SOD1 gene mutation and ALS. Preclinical studies in a SOD1-ALS mouse model demonstrated that APB-102 greatly enhanced survival in affected mice. Relevant SOD1 reduction in spinal cord motor neurons also was demonstrated in rodents, as well as in non-human primates at proposed clinical doses.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by loss of motor neurons, leading to muscle weakness and eventual paralysis. Most patients face mortality within five years of disease onset due to respiratory failure. ALS can be caused by multiple genetic mutations and can be sporadic (spontaneous mutations) or familial (inherited mutations). Familial mutations account for approximately ten percent of ALS cases, and of these, approximately twenty percent are linked to a mutation in the SOD1 gene that codes for the enzyme superoxide dismutase 11. SOD1-linked ALS is most likely caused by toxic mutant forms of the superoxide dismutase 1 (SOD1) protein (a gain-of-function mutation). Current approved ALS treatments only delay disease progression without addressing the underlying genetic causes of the disease.

The U.S. Food and Drug Administration has cleared the investigational new drug (IND) application for AMT-162 and has granted Orphan Drug and Fast Track designations.