FMR 1-SLS: Improving Fragile X diagnosis using amplification-free single locus ta

DESCRIPTION (provided by applicant): Of the approximately 10 million people in the US living with paralysis, 15,000 are the result of spinal cord injury each year. The first year of car can range from 322,000- 986,000, with lifetime costs of 1.4-4M forsomeone 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 fromspinal 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 years post-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 daily epidural stimulation and motor training, voluntary control of both legs was evident in the presence of epidural stimulation, whereas completeparalysis remained in absence of epidural stimulation. We will advance these discoveries with the use of non-invasive stimulation of the cervical cord to improve arm and hand function following SCI. Central to this proposal is our discovery of a painlesselectrical single-channel (stimulation of one part of the spinal cord) and dual-channel (stimulation of two different parts of the cord) paradigm that can be applied to the surface of the skin, termed transcutaneous electrical stimulation (TES), bypassingthe need for a surgically-implanted electrode array. In the first phase of this proposal we will demonstrate proof-of-principle that stimulation of the cervical spinal cord can improve 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 dual-channel commercial prototype. This commercial productwill undergo testing similar to the proof- of-principle device. This device will then be tested in subjects with cervical spinal cord injury and evaluated with a machine-learning protocol. This Phase I proposal will deliver a device that can painlessly andnon-invasively aid in the recovery of SCI by delivering a specific electrical stimulation paradigm to the cervical cord that improves use of the arms and hands. PUBLIC HEALTH RELEVANCE PUBLIC HEALTH RELEVANCE: Electrical modulation of the spinal cord can restore voluntary motor function in patients with spinal cord injury, a phenomenon we have demonstrated with both implantable electric devices and devices that provide electrical stimulation to the cord through the surface of the skin. Here, wepropose to build and test a refined device that stimulates the skin above the spinal cord at two different locations to improve arm and hand motor function in spinal cord injury patients.