Stimulating axon regrowth can help promote functional regeneration after spinal cord injury (SCI), a new study has discovered.
Through the activation of MAP2K signaling by genetic engineering, or non-invasive repetitive transcranial magnetic stimulation (rTMS), this can promote corticospinal tract (CST) axon sprouting.
The study in mice, led by Burke Neurological Institute, suggests that rTMS might be a valuable treatment option for humans living with SCI. Clinical trials are now underway to establish the feasibility for this.
Facilitating axon regeneration in the injured central nervous system (CNS) remains a challenging task. The failure of mature CNS neurons to activate cell-intrinsic growth mechanisms and regenerate injured axons severely hinders functional recovery after a traumatic brain or spinal cord injury, which requires the development of effective new therapies.
Building on previous research, the team from BNI hypothesised that RAF signalling regulates an intrinsic axon growth program and that its activation could enable re-growth of adult mammalian CNS axons after SCI.
They found that CST axon sprouting and regeneration was seen in different experimental models of SCI in mice.
According to Dr Xiaofei Guan, a postdoctoral research fellow at BNI who conducted the experiments, newly sprouting CST axons formed synapses with local spinal circuits and further resulted in improved motor functional recovery.
rTMS has been emerging as a promising strategy to enhance recovery in patients with spinal cord or brain injury, but the underlying plasticity mechanisms and the full therapeutic potential of these approaches remain unknown.
The BNI research team found that a course of daily high-frequency rTMS sessions activated MAP2K signalling and modulated the expression of a set of regeneration-related transcription factors in the same way as genetic BRAF activation.
Endogenous MAP2K activity was required for enhanced CST sprouting, regeneration and functional recovery in HF-rTMS treated SCI model mice.
The researchers believe these results collectively demonstrate a central role of MAP2K signalling in augmenting the growth capacity of mature corticospinal neurons, and suggest that HF-rTMS might have potential for treating spinal cord injury by modulating MAP2K signalling.
The BNI team has begun clinical trials testing the HF-rTMS protocol on able-bodied individuals and SCI patients. If successful, HF-rTMS could emerge as a non-invasive, low risk treatment option to facilitate axon regeneration, alone or in combination with other additional interventions, for SCI or other individuals who may benefit from CNS circuitry repair.
