OPTOGENETIC THERAPY FOR INHIBITION OF MUSCLE SPASMS AND HYPERREFLEXIA AFTER SPINAL CORD INJURY

Following spinal cord injury (SCI), many patients develop peripheral complications marked by muscle hyperactivity, such as spasticity. These symptoms—often painful and disruptive—can significantly hinder rehabilitation efforts. Current treatment options frequently carry substantial side effects and offer only limited relief. To better understand and address these challenges, we established a model of incomplete SCI in mice. These animals exhibit restricted hindlimb mobility, clonus, and prolonged spasms. Electrophysiological evaluation of Hoffmann’s reflex confirms pronounced hyperreflexia, reflecting underlying neural hyperactivity. To treat this dysfunction, we are developing a targeted optogenetic therapy aimed at selectively inhibiting overactive muscle groups. Our two-part strategy begins with intramuscular delivery of AAV viral vectors that drive expression of inhibitory opsins in spinal motor neurons. This is followed by implantation of a soft optoelectronic nerve cuff that contains LEDs around the sciatic nerve, enabling precise light delivery to activate opsin-expressing motor axons and suppress muscle activity. In acute electrophysiological tests, optical activation of the inhibitory opsin JAWS significantly reduced electrically induced muscle responses. Moreover, in mice with chronically implanted nerve cuffs, both normal locomotor function and spasm-related activity could be disrupted upon JAWS activation. With successful validation in murine models, we are now preparing to advance this therapy to trials in nonhuman primates.