AAV9-CMV-sKL

AAV9-CMV-sKL is an experimental gene therapy candidate utilizing an adeno-associated virus serotype 9 (AAV9) vector to deliver the gene for the secreted form of alpha-Klotho (sKL) under the control of a cytomegalovirus (CMV) ubiquitous promoter. Developed by researchers at the Universitat Autònoma de Barcelona and the Vall d'Hebron Institut de Recerca (VHIR), this therapy is being investigated for the treatment of Amyotrophic Lateral Sclerosis (ALS). The secreted form of alpha-Klotho is a circulating anti-aging factor that exhibits pleiotropic neuroprotective and myoregenerative properties, including anti-inflammatory and anti-oxidative effects, modulation of synaptic homeostasis, and support of mitochondrial resilience. In preclinical studies using SOD1G93A mice, intrathecal administration of AAV9-CMV-sKL has shown the potential to preserve motor neuron function and improve neuromuscular transmission, with additive benefits observed when combined with muscle-targeted gene therapies.