Neuron-targeted caveolin-1 improves neuromuscular function and extends survival in SOD1G93A mice

What is it about?

Amyotrophic lateral sclerosis (ALS), better known as Lou Gehrig's disease, is a progressive neurodegenerative disease resulting from loss of motor nerve cells (a.k.a. neurons) in the brain and spinal cord. ALS symptoms include diffuse muscle weakness, muscle loss, uncontrolled muscle contraction (a.k.a. spasticity), and paralysis, and short life expectancy (2-5 years). One approach to combat ALS is to deliver pro-survival growth factors to prevent loss of these motor neurons, yet this is dependent upon expression and the proper cellular localization of key protein receptors that in turn bind these growth factors. Our group has shown that when we over-express a scaffolding protein called caveolin (i.e., Cav, which is analogous to a coat hanger) specifically in neurons, these growth factor receptors move to the membrane of neurons, which allows them to bind these pro-survival growth factors. The goal of the current project is to deliver a vector that contains the genetic material for Cav, with selectivity to only increase Cav expression in neurons within the brain and spinal cord of ALS rodents. The objective is that delivery of this vector in combination with drugs that stimulate these growth factor receptors (i.e., agonists) and inhibit neurotoxic microglia will protect motor neurons in the brain and spinal cord of early on-set, moderate on-set, and late-stage ALS rodents as well as regenerate motor neurons in late stage ALS rodents (a.k.a. functional neuroplasticity). Our ultimate objective is to extend life expectancy in both early and late stage ALS patients.

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