Amyotrophic lateral sclerosis (ALS), also known as motor neuron disease or Lou Gehrig’s disease, is a devastating and fatal neurodegenerative disease, characterized by rapid degeneration of upper and lower motor neurons in the brain and spinal cord, leading to progressive paralysis and death. Patients with ALS survive an average of 2 – 5 years after their diagnosis. Each year, more than 15,000 people in the U.S. and EU are diagnosed with ALS and an estimated 55,000 are living with this disease. Currently, treatment options for patients with ALS are extremely limited with no drugs that significantly slow disease progression.
While approximately 90% of ALS patients have no known family history of the disease, approximately 10% of ALS patients have a known genetic cause for their disease. An expanded hexanucleotide GGGGCC repeat in the first intron of the chromosome 9 open reading frame 72 (C9orf72) gene is the most common genetic defect implicated in ALS (C9orf72-ALS), accounting for approximately 34% of familial ALS cases and approximately 12% of all ALS cases. The expanded GGGGCC repeats cause neuronal dysfunction by a variety of mechanisms including generation of toxic RNA foci formation of abnormal dipeptide-repeat protein aggregates and a reduction of C9orf72 expression.
AGTC is investigating a unique platform that potentially delivers the best of gene silencing and gene augmentation therapy in a single trivalent vector. Using this approach, we aim to simultaneously address both the toxic gain-of-function and loss-of-function caused by mutations of C9orf72 while augmenting with wild type protein. We hope to transform the lives of patients living with C9orf72-ALS through this novel gene therapy strategy.
© agtc. All rights reserved.