Preclinical Testing of Intraspinal Microstimulation for Restoring Walking After Severe SCI
Abstract
Objectives and Rationale: The ultimate solution for spinal cord injury (SCI) is to regenerate the damaged portions of the spinal cord and restore the way is used to be connected prior to the injury. However, this has been extremely challenging so far, and other ways for restoring function after SCI have been studied. One very effective way has been to use electrical stimulation to activate muscles and nerves to restore functions such as breathing, emptying the bladder, using the hands, and standing. But although electrical stimulation has been tested for restoring walking after severe SCI, it has not been very successful. Instead, recent research has proposed that stimulating the spinal cord itself below the level of the injury may activate the walking-related networks that are still in the spinal cord, and may restore the ability to walk that way. Two ways for stimulating the spinal cord have been tested. One places stimulating electrodes on the surface of the spinal cord, called epidural spinal cord stimulation (ESCS), and the other places very fine, micro-implants inside the spinal cord, called intraspinal microstimulation (ISMS). ESCS has been tested in five people with severe SCI in two different studies, and found that this stimulation method when combined with intensive locomotor training therapy for more than 1.5 years, some participants (three of the five) are able to walk for short distances (less than 100 meters). ISMS has not been tested in humans yet, but has been tested in several animal models. The procedure was found to be safe and the micro-implants remain stable. Very importantly, ISMS in animal models of SCI was able to produce walking for long distances (about 1,000 meters)! The goal of this study is to take a critical step in preparing ISMS for testing in humans in the future. Specifically, this study will develop an ISMS system that can be fully implanted (in other words, no wires piercing through the skin to connect to an external stimulator), and will test the system in adult Yucatan pigs, which have the same size and shape of the spine and spinal cord as that in humans. Ultimate Applicability of the Proposed Work: By the end of the study, we would have demonstrated the feasibility, safety, and functionality of ISMS in restoring walking after severe SCI. This is a critical step to determining the future applicability of ISMS in persons with SCI. Importantly, we would have developed the necessary platform upon which we can develop an ISMS system that would meet the regulatory requirements set out by the FDA for implanted medical devices. We would have also learned what we should expect when testing ISMS in humans in the future—from the implantation procedure, to how to ensure that the system remains stable, and how the system improves walking capacity over time. The immediate next step will be to work with the FDA to ensure that our design of the system for the first-in-human testing will meet the regulatory requirements. Once the system is designed and receives the FDA’s approval to test in humans by securing an Investigational Device Exemption (IDE), we will begin testing in a few human volunteers (4-5 people) with severe SCI. This would allow us to do the pivotal testing that will determine the viability of ISMS as a means for restoring functional walking to people with SCI. Projected Timeline to Achieve Person-Related Outcome: If the outcomes of the work proposed in this application are successful, the next 3-5 years will focus on developing the implantable system that meets FDA regulations. The following 3-5 years will then focus on the first-in-human Early Feasibility testing of the system. If the outcomes are positive, commercial uptake of the system will ensure that testing will continue in more and more people, until the system becomes reimbursable. The system may then become available to all persons with SCI who can benefit from it. Persons with severe thoracic and low cer
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010875
Entities
People
- Vivian K Mushahwar
Organizations
- United States Army
- University of Alberta