Inhibition of retinoic acid metabolism for reversal of cognitive deficits in AD

A Theranostic Tool to Assess and Enable Spared Spinal Motor Function After SCI NeuroEnabling Technologies, Inc. RESEARCH and RELATED Other Project Information 7. PROJECT SUMMARY Of the approximately 10 million people in the US living with paralysis, 15,000are the result of spinal cord injury each year. The first year of care can range from 322,000- 986,000, with lifetime costs of 1.4-4M for someone injured at 25 years of age. In addition to potentially devastating sensorimotor disturbances, there is a huge financial cost, estimated to be 13.55B in medical care, therapy, and lost productivity nationwide. Until very recently, the recovery from spinal cord injury (SCI) was bleak, with little hope of restoring motor function. To address this we have demonstrated that the physiological state of the spinal circuitry of rats and cats can be modulated with epidural stimulation to generate voluntary limb motor function over a range of speeds, loads, and directions, a finding we have extended to humans. Three yearspost-injury, a motor complete spinal cord injured human subject was implanted with an epidural electrode array over the lumbosacral spinal cord. In less than one month after implantation, the subject could stand independently, and after 7 months of dailyepidural stimulation and motor training, voluntary control of both legs was evident in the presence of epidural stimulation, whereas complete paralysis remained in absence of epidural stimulation. We will advance these discoveries with the use of non-invasive stimulation of the lumbosacral cord to improve lower limb function following SCI. Central to this proposal is our discovery of a painless electrical multi-channel (stimulation of multiple parts of the spinal cord) theranostic tool that can be applied to the surface of the skin, termed transcutaneous spinal cord electrical stimulation (TESCS), bypassing the need for a surgically-implanted electrode array. In the first phase of this proposal we will demonstrate proof-of-principle that stimulation of the lumbosacral spinal cord can assess spared spinal motor function by: 1) Testing responses to transcutaneous electrical stimulation in subjects with spinal cord injury; and 2) defining the operational parameters of electrical stimulation that that are most effective using a machine-learning protocol, and 3) produce a multi-channel commercial prototype. This commercial product will undergo testing similar to the proof-of- principle device. This device will then be tested in subjects with cervicothoracic spinalcord injury and evaluated with a machine-learning protocol. This Phase I proposal will deliver a device that can painlessly and non-invasively aid in the assessment and recovery of SCI by delivering a specific electrical stimulation paradigm to the lumbosacral cord that improves use of the lower limbs. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: A Theranostic Tool to Assess and Enable Spared Spinal Motor Function After SCI NeuroEnabling Technologies, Inc. PROJECT NARRATIVE It now seems possible to apply three interventions: transcutaneous stimulation, administration of pharmacological agents, and motor training, to assess and enable the excitability of spared neural circuits in humans with a thoracic spinal cord injury (SCI), thus enabling these individuals to regain use of their legs. This enabling effect is similar to that observed with improved postura and locomotor function after a mid-thoracic SCI in which epidural stimulation was used. We will build and demonstrate a multi-channel transcutaneouselectrical spinal cord stimulation theranostic tool that we propose will allow assessment and enabling of lower limb function following a cervicothoracic spinal cord injury.