Inhibiting an inhibitor: a decoy to recover dexterity after spinal cord injury

Brain, 2020 · DOI: 10.1093/brain/awaa175 · Published: June 1, 2020

Spinal Cord Injury Regenerative Medicine Neurology

Simple Explanation

This article discusses a potential new therapy for spinal cord injury that involves blocking the action of inhibitory molecules that prevent nerve regeneration. The approach uses a 'decoy' molecule to bind to these inhibitors, allowing nerve growth and improved function. Researchers tested a Nogo receptor decoy (AXER-204) in rodents and monkeys with spinal cord injuries. The study focused on cervical injuries, which are the most common in humans and often affect hand function. The study found that the decoy molecule was safe and effective in improving forelimb use in monkeys with cervical spinal cord injuries. This improvement was linked to the regeneration of a major motor pathway in the spinal cord.

Study Duration

7-16 months

Participants

13 African green monkeys

Evidence Level

Not specified

Key Findings

1
AXER-204 showed no toxicity in rodents or primates.
2
Monkeys treated with AXER-204 showed an increase in right forelimb usage and a decline in left-side preference over time.
3
Corticospinal tract labeling revealed significantly increased axon density below injury only in animals treated with AXER-204.

Research Summary

This commentary discusses a study that investigated the use of a Nogo receptor decoy (AXER-204) to promote recovery after spinal cord injury in non-human primates. The study found that AXER-204 was safe and effective in improving forelimb function and promoting corticospinal tract regeneration. The observed recovery in hand function is particularly relevant, as this is a high priority for individuals living with spinal cord injuries. The fact that AXER-204 was effective at a chronic post-injury time point is also significant. A clinical trial for AXER-204 in participants with chronic spinal cord injury is currently recruiting, and the authors express hope that this will be one of a range of neuroplasticity-promoting therapies to become available in the clinic.

Practical Implications

Clinical Translation

The favorable toxicity profile and efficacy in primates support the clinical progression of AXER-204 as a potential therapy for spinal cord injury.

Combination Therapy

The recovery observed with AXER-204 treatment might be further enhanced if combined with additional therapies, such as those targeting scar-associated inhibitors or boosting regenerative capacity.

Rehabilitative Training

AXER-204 would likely be combined with a program of rehabilitative training to harness the neuroplasticity potential of the drug.

Study Limitations

1
Pain sensitivity was not specifically tested.
2
Some additional behavioral time points might have provided a more complete understanding of the time course of recovery.
3
Some information on skill and dexterity while handling, holding and grasping food, in addition to hand use preference, would also have been informative.

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