REVIEW article
Front. Surg.
Sec. Neurosurgery
This article is part of the Research TopicAdvances in Nerve Repair and RegenerationView all 6 articles
Treatment of spinal cord injury, by restoration of neuronal networks using a combination of surgery and KCL-286 an retinoic acid receptor (RAR) orally available drug
Provisionally accepted
- King's College London, London, United Kingdom
Select one of your emails
You have multiple emails registered with Frontiers:
Notify me on publication
Please enter your email address:
If you already have an account, please login
You don't have a Frontiers account ? You can register here
The most complicated nerve injury occurs in the spinal nerves. Following traumatic injury at the nerve root attachment to the spinal cord(avulsion), there is degeneration of nerve fibres in the root as well as the spinal cord. The result for the patient is paralysis with sensory loss and typical severe excruciating pain. An obvious fundamental surgical treatment for such injuries is to re-create continuity for the ruptured spinal nerve as well as for the roots detached from the spinal cord. Reimplanting motor spinal roots leads to neuronal growth within the spinal cord and distally in the peripheral nerves resulting in recovery of shoulder and proximal arm muscles. Sensory function cannot be restored surgically from dorsal root to spinal cord replantation due to impediment of regrowing sensory fibres at the spinal cord glia scar. However, when a ganglionectomised dorsal root-in effect a peripheral nerve conduit-was implanted into the spinal cord sensory system intramedullary (secondary) sensory neurons extended distally, resulting in recovery of some sensory function. Patients profited from this surgery with better functional performance without movement synkinesis and reduced pain. Full functional restoration after a nerve injury cannot be achieved by means of surgery alone due to impediment of regrowing sensory fibres at the spinal cord glia scar. To identify pathways required for adult spinal cord injury repair embryonic axogenesis was studied. From this a key regulator, the retinoic acid receptor (RAR) was identified. This signalling cascade can be reactivated in the injured adult nervous system with the orally available drug KCL-286. This drug has been shown to be safe and tolerated in humans at doses predicted to be used in human spinal cord injuries to give functional recovery. Therefore, the combination of surgical root implantation and KCL-286 represents a promising therapeutic strategy to improve the quality of life for patients with root avulsions and the broader spinal cord injury patient population.
Keywords: avulsion brachial plexus injury, drug, nuclear receptor signalling, orally available, Retinoic acid, spinal cord injury
Received: 10 Nov 2025; Accepted: 23 Jan 2026.
Copyright: © 2026 Corcoran and Carlstedt. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence: Jonathan Corcoran
Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.