Currently, spinal cord injury has no effective treatment; Physical rehabilitation can help patients regain some mobility, but for severe cases the results are extremely limited due to the lack of natural regeneration of spinal neurons after an injury. However, in a study published on September 20 in the open access journal PLOS Biology, researchers led by Simone Di Giovanni at Imperial College London in the UK show that weekly treatments with an epigenetic activator can help the growth of sensory and motor neurons in the spinal cord. when given to mice 12 weeks after severe injury.
Building on their past success, the researchers used a small molecule called TTK21 to activate the genetic programming that induces axon regeneration in neurons. TTK21 changes the epigenetic state of genes by activating the CBP/p300 family of coactivator proteins. They tested the TTK21 treatment in a mouse model of severe spinal cord injury. The mice lived in an enriched environment that gave them opportunities to be physically active, as is encouraged in human patients.
Treatment began 12 weeks after a severe spinal cord injury and lasted 10 weeks. The researchers found several improvements after TTK21 treatment compared to control treatment. The most noticeable effect was that more axons sprouted in the spinal cord. They also found that retraction of motor axons above the point of injury stopped and that sensory axon growth increased. These changes are likely due to the observed increase in gene expression related to regeneration. The next step will be to further enhance these effects and cause the regenerating axons to reconnect with the rest of the nervous system so that the animals can regain their ability to move easily.
This work shows that a drug called TTK21 that is administered systematically once a week after chronic spinal cord injury (SCI) in animals can promote neuronal regrowth and an increase in synapses needed for neuronal transmission. This is important because chronic spinal cord injury is an incurable condition where neural regrowth and repair fail. We are now exploring the combination of this drug with strategies that bridge the spinal cord gap such as biomaterials as possible avenues to improve disability in LM patients.”
Simone Di Giovanni, Imperial College London
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Journal reference:
Müller, F., et al. (2022) CBP/p300 activation promotes axon growth, sprouting and synaptic plasticity in chronic experimental spinal cord injury with severe disability. PLOS Biology. doi.org/10.1371/journal.pbio.3001310.