OPTOGENETIC THERAPY TO TREAT SPASTICITY IN A MOUSE MODEL OF SPINAL CORD INJURY

Spasticity is a sensorimotor condition affecting more than 12 million people worldwide and presents a large unmet clinical need. It is highly prevalent across neurological disorders, occurring in 79% of individuals after spinal cord injury, 85% with cerebral palsy, 35% after stroke, and 80% of patients with multiple sclerosis. Spasticity is characterized by involuntary, painful, muscle spasms, hypertonicity, hyperreflexia and clonus. Current treatments are often ineffective due to slow pharmacokinetics, tolerance, or nonspecific side effects, highlighting the urgent need for therapies with greater spatiotemporal precision.To address this, we are developing an optogenetic therapy for spasticity composed of two elements: a motor‑neuron‑targeted gene therapy to deliver light‑sensitive inhibitory opsins to affected muscles, and a soft, stretchable optoelectronic nerve cuff containing micro‑LEDs for photo-stimulation of peripheral nerves. Focusing on the gene therapy component, we have achieved efficient retrograde transduction and opsin expression in spinal motor neurons that innervate specific muscles. Leveraging cell‑type‑specific targeting strategies and viral serotype selection, we demonstrate improved specificity and transduction efficiency, resulting in the efficient optogenetic inhibition of muscle function in vivo.By combining cell‑targeted gene therapy with implantable, biocompatible optoelectronic devices, this platform has the potential to transform treatment for a range of neurological disorders. With modifications to the gene therapy component, the same strategy could be adapted to manage other peripheral nervous system conditions, including control of micturition, pain alleviation, and restoration of motor function.