AAV-NRIP

AAV-NRIP is an investigational gene therapy that utilizes an adeno-associated virus (AAV) vector to deliver the human nuclear receptor interaction protein (NRIP) gene. NRIP is a multifunctional protein involved in muscle contraction, sarcomere integrity, and neuromuscular junction (NMJ) stabilization through interactions with calmodulin, α-actinin 2, and the acetylcholine receptor. Loss of NRIP leads to progressive motor neuron degeneration and NMJ abnormalities resembling amyotrophic lateral sclerosis (ALS). In preclinical studies using SOD1 G93A ALS mouse models, intramuscular administration of AAV-NRIP restored NRIP expression in skeletal muscle and spinal cord, improved motor function, increased myofiber size and slow myosin expression, ameliorated NMJ degeneration and axon terminal denervation at NMJs, increased α-motor neuron counts, enhanced compound muscle action potential (CMAP), and reduced muscle atrophy. These findings suggest that AAV-NRIP may be a promising therapeutic candidate for ALS by targeting both muscular and neuronal pathology[1][3].