Polyethylene Glycol (PEG)-Mediated Fusion (PEG Fusion) Repair of Mixed Motor-Sensory Acute Peripheral Nerve Injuries (PNI) for Rapid and Immediate Improvement in Outcome
Abstract
Background: Major mixed motor/sensory nerves of the extremities provide critical sensation and muscle function that allow us to use our arms/hands and legs/feet for everything we do in everyday life. PNI can be devastating by robbing the body of its ability to function causing severe disability, pain, loss of duty or employment, and increased burdens on family, friends and the health system. Our goal is to drastically improve outcomes after repair or reconstruction of PNI by attempting to reconnect cells that have been divided in nerve injury and prevent them from degenerating in a normal process called Wallerian Degeneration (WD), which ALL PNI injuries are currently destined to undergo. Once this process is underway, nerve recovery is destined to progress through the normal, slow, inefficient biological process of nerve regeneration by growing the proximal stump of the divided nerve cell distally toward the target it used to innervate at a historically cited rate of ~1 mm/day in healthy young adults. By reconnecting these cells within 24 hours of injury using a process called PEG fusion and utilizing a substance that is already used safely in humans for multiple applications, outcomes could potentially be much greater, as evidenced by the PEG fusion research performed by ourselves and others in animal experiments, which resulted in a rapid return of measurable motor function and restoration of behavior. Objective: We will begin the translation process for PEG fusion into humans by assessing its safety when used on major upper extremity PNI. We will assess this process in a phase 1 study in humans to make sure it does not cause harm and secondarily for any possible benefit in nerve recovery outcome. We will also compare the data from this trial to data we are already collecting for upper extremity major PNI across a spectrum of upper extremity nerve injuries and repair/reconstruction methods in the METRC NERVE study ongoing for almost 4 years now. This would directly address the focus area of Peripheral Nerve Regeneration by immediate reconnection of severed peripheral nerves to prevent WD and indirectly enhance all other areas of encouragement via the downstream effect of restoring the nerve-motor unit and preventing those problems. Applicability/Impact: Over a 5-year time span, we will train surgeons to perform this technique on animals then enroll and randomize 40 patients (injured civilians and military members from five health system/university sites and two military treatment facilities) into this study, with 20 receiving PEG fusion and 20 not receiving PEG fusion. We will follow them for 2 years and compare outcomes between groups as well as to the METRC NERVE study patients. If the process proves safe and ultimately proves itself beneficial, it would be applicable to all persons with a peripheral nerve injury if they could be treated in the immediate post-injury period. We believe the risk to be very low. We have not observed morbidity in animals from the PEG fusion process and believe that, if it is not success, the nerve is still capable of standard regeneration, as evidenced by a sudden improvement in animal function after PEG fusion, then a continuous improvement afterwards that mirrors normal nerve regeneration and is additive to the original advantage provided by PEG fusion. In fact, this would cause a drastic change in how PNI is treated throughout the world by turning this injury into an emergency or urgent condition so that the nerve could be PEG fused prior to the onset of WD. The potential benefit for recovery, in particular for those with motor nerve injuries that operate extremity muscles, would be potentially months to years saved in nerve regeneration time and possibly a higher expected level of function than possible with standard nerve regeneration. Overall Benefit: The ultimate impact and benefit to military Service members, Veterans, families, caregivers, and clinicians are
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Mar 10, 2021
- Source ID
- W81XWH2010825
Entities
People
- Jamie Shores
Organizations
- Johns Hopkins University
- United States Army