Research uncovers ‘brake’ that blocks spinal cord repair

Researchers in South Korea have identified the molecular “brake” that halts spinal injury repair.

They found that GABA, a chemical messenger that normally dampens nerve signals,  is produced in excess by astrocytes, star-shaped support cells, after injury.

This happens through the enzyme monoamine oxidase B (MAOB), which becomes overactive.

GABA was shown to suppress brain-derived neurotrophic factor (BDNF) and its receptor TrkB, both essential for nerve growth.

Without these growth signals, damaged fibres cannot regenerate, leading to paralysis.

Director C. Justin Lee of the Institute for Basic Science said: “This study identifies a direct molecular pathway that suppresses neural regeneration after spinal cord injury and presents a strategy to overcome it.

“Unlike existing treatments, this offers a fundamentally new therapeutic approach.

“The multi-level validation in rodents, primates, and Phase I clinical trials provides strong evidence that this drug candidate could translate into real treatment for patients.”

Until now, recovery failure was blamed on the glial barrier, a scar formed by rapidly multiplying astrocytes and other glial cells.

This barrier helps protect the wound early on but was thought to later block regrowth. The new work shows the mechanism is chemical as well as physical.

The team had previously shown that reactive astrocytes produce excess GABA via MAOB in Alzheimer’s disease.

They tested whether the same process occurs after spinal cord injury and confirmed it acts as a molecular brake on recovery.

Animal models supported the theory. Suppressing MAOB in spinal astrocytes allowed axons to regrow and restored hindlimb motor function.

Increasing MAOB caused severe tissue loss and almost no recovery.

The researchers also tested KDS2010, a drug that blocks MAOB, in mice with spinal injuries.

Treated animals had fewer hindlimb slips in ladder-walking tests, with robust axonal regrowth at the injury site.

Tissue analysis showed reduced cavity formation and more remyelinated axons – rebuilt protective nerve sheaths.

Similar benefits appeared in non-human primates, where the treatment preserved tissue and improved neural protection. KDS2010 has already completed a Phase I safety trial in healthy adults.

Professor Ha Yoon of Yonsei University College of Medicine added: “KDS2010 has already demonstrated safety in a Phase I clinical trial, and we plan to proceed with Phase II trials to evaluate its efficacy in spinal cord injury patients.

“Moreover, we aim to investigate whether the MAOB–GABA pathway plays a role in other neurological disorders, broadening its potential applications into a more comprehensive therapeutic platform.”