Combined with anti‐Nogo‐A antibody treatment, BDNF did not compensate the extra deleterious motor effect caused by large size cervical cord hemisection in adult macaques

CNS Neuroscience & Therapeutics, 2020 · DOI: 10.1111/cns.13213 · Published: February 1, 2020

Spinal Cord Injury Neurology Rehabilitation

Simple Explanation

This study investigates whether adding BDNF (brain-derived neurotrophic factor) to anti-Nogo-A antibody treatment can improve recovery of hand dexterity in monkeys with spinal cord injuries. Anti-Nogo-A antibodies help nerve fibers regenerate, while BDNF promotes nerve growth and protects damaged neurons. The researchers created larger spinal cord injuries in some monkeys to see if the combined treatment could overcome the increased damage. They compared the recovery of hand function in monkeys treated with a control antibody, anti-Nogo-A antibody alone, and the combined anti-Nogo-A antibody and BDNF treatment. The study found that while anti-Nogo-A antibody treatment alone improved hand dexterity, adding BDNF did not provide additional benefits and, in some cases, seemed to hinder recovery, especially in monkeys with larger injuries. This suggests that BDNF may not enhance the effects of anti-Nogo-A antibody treatment for spinal cord injury recovery.

Study Duration

About 200 and 350 days

Participants

18 adult macaque monkeys: control monkeys (n = 6), anti-Nogo-A antibody-treated monkeys (n = 7), and anti-Nogo-A antibody and BDNF-treated monkeys (n = 5)

Evidence Level

Level II: Therapeutic, experimental study in non-human primates

Key Findings

1
Monkeys treated with anti-Nogo-A antibody alone showed functional recovery of manual dexterity performances close to prelesion ones, irrespective of lesion size.
2
The group receiving combined anti-Nogo-A antibody and BDNF treatment had significantly lower functional recovery compared to the anti-Nogo-A antibody-treated monkeys, even though some in the combined treatment group had larger lesions.
3
The functional recovery of score or contact time was significantly different when a control antibody was applied, as compared to administration of the anti‐Nogo‐A antibody alone or to administration of the combined treatment.

Research Summary

This study investigated whether adding BDNF to anti-Nogo-A antibody treatment could enhance functional recovery after spinal cord injury (SCI) in adult macaque monkeys. Previous research has shown that anti-Nogo-A antibodies promote axonal regeneration and functional recovery, while BDNF stimulates neurite outgrowth. The researchers compared three groups of monkeys: a control group, a group treated with anti-Nogo-A antibody alone, and a group treated with a combination of anti-Nogo-A antibody and BDNF. The size of the cervical cord hemisection was controlled to assess if BDNF could compensate for larger lesions. The study found that while anti-Nogo-A antibody treatment alone improved manual dexterity, the addition of BDNF did not enhance recovery and, in some cases, appeared to reduce it, particularly in monkeys with larger lesions. This suggests that BDNF may not provide a synergistic benefit when combined with anti-Nogo-A antibody treatment for SCI recovery in primates.

Practical Implications

Clinical Implications

The findings suggest that BDNF may not be an effective adjunct therapy to anti-Nogo-A antibody treatment for spinal cord injury recovery. Further research is needed to understand the potential negative effects of BDNF in this context.

Research Implications

Future studies should explore the specific mechanisms by which BDNF may interfere with the benefits of anti-Nogo-A antibody treatment. This could involve investigating the effects of BDNF on different neuronal populations or its impact on pain and spasticity.

Therapeutic Strategies

The results highlight the importance of carefully evaluating the potential benefits and risks of combining different therapeutic agents for spinal cord injury. Further research is necessary to identify alternative neurotrophic factors or treatment strategies that can effectively enhance recovery in conjunction with anti-Nogo-A antibody therapy.

Study Limitations

1
Small sample size in the combined treatment group (n=5).
2
Potential variability in lesion location and extent, despite efforts to control it.
3
The study focused solely on manual dexterity, and the findings may not generalize to other functional outcomes.

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