Abnormal urethral sphincter contractions can prevent bladder emptying and cause significant morbidity and reduction in quality of life after neurological disease or injury. Existing treatment options are of limited effectiveness, destructive, or possess systemic side effects, reducing patient acceptance of these therapies. Electrical stimulation of sacral motor nerve roots can restore bladder voiding after SCI; however only when combined with the irreversible surgical transection of the sensory spinal nerve roots (i.e., a dorsal rhizotomy) to eliminate reflex contractions of the urethral sphincter that otherwise prevent voiding. Other effects of the rhizotomy (loss of remaining sensation, reflex sexual function and reflex defecation) limit the clinical acceptance of this procedure. The goal of this project is to develop a neural prosthesis that uses electrical pudendal nerve block to eliminate urethral sphincter activation and allow bladder voiding. High frequency nerve block provides, rapid, complete and reversible local nerve conduction block. We have demonstrated that bilateral pudendal nerve block can prevent urethral sphincter activation and produce bladder voiding equivalent to nerve transection in animals. We have also demonstrated that pudendal nerve block can be achieved with available nerve cuff electrodes approvable for human studies. Demonstration of electrical pudendal block and improved voiding in humans is the next major milestone to translate this approach to humans. Implantation of a pudendal nerve cuff electrode for the feasibility study requires FDA approval of an investigational device exemption (IDE). This Phase I project will identify and prepare the necessary components for an FDA investigational device exemption (IDE) application and conduct a pre-IDE meeting with the FDA. This process and the pre-IDE FDA meeting will define the effort and resources required to obtain FDA approval to conduct the human feasibility trial in the next phase (next application). This Phase I project will also establish a screening procedure using temporary anesthetic pudendal nerve block and identify initial candidates for the implanted device. At the end of this Phase I project, we will be ready to assemble and submit an IDE to conduct the human feasibility study in the next phase. This approach is expected to expand the population of individuals who could benefit from neural prostheses to control the bladder, and thereby improve their health and quality of life while reducing costs to the healthcare system.
Public Health Relevance: Abnormal urethral sphincter contractions can prevent bladder emptying. This project begins the translation of a neural prosthesis to restore bladder voiding using electrical pudendal nerve block of the urethral sphincter.
Public Health Relevance Statement: Abnormal urethral sphincter contractions can prevent bladder emptying. This project begins the translation of a neural prosthesis to restore bladder voiding using electrical pudendal nerve block of the urethral sphincter.
NIH Spending Category: Assistive Technology; Bioengineering; Clinical Research; Injury (total) Accidents/Adverse Effects; Injury - Trauma - (Head and Spine); Neurodegenerative; Neurosciences; Prevention; Rehabilitation; Spinal Cord Injury
Project Terms: Adverse effects; Anesthetics; Animals; Bilateral; Bladder; Bladder Control; Chemicals; Clinical; clinical efficacy; Clinical Research; cost; Cytolysis; Data; Defecation; design; Devices; Dorsal; Effectiveness; Electric Stimulation; Electrodes; Elements; Esthesia; Feasibility Studies; Feedback; Frequencies (time pattern); Goals; Health; Health Care Costs; Healthcare Systems; Human; implantable device; implantation; Implanted Electrodes; improved; Individual; innovation; Investigation; Local Anesthetics; meetings; Morbidity - disease rate; Motor; Nerve; Nerve Block; nervous system disorder; Nervous System Trauma; Neural Conduction; neural prosthesis; Neurologic; operation; Operative Surgical Procedures; patient population; Patients; Phase; Plant Roots; Population; prevent; Procedures; Process; Protocols documentation; prototype; Proxy; Quality of life; Reflex action; Reporting; Research; Resources; Rhizotomy procedure; Screening procedure; Sensory; Sex Functioning; Spinal cord injury; Spinal nerve root structure; System; Technology; TimeLine; Translating; Translations; Urethral sphincter
