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Epigenetic therapy supports spinal cord regeneration in mice.
Currently, there is no effective treatment for spinal cord injury. Physical rehabilitation can help patients regain some mobility, but in severe cases, results are severely limited due to the failure of spinal nerve cells to regenerate normally after an injury.
However, new research led by Professor Simon DiGiovanni And the Published in the magazine Biology Plus He shows that weekly treatments with an epigenetic activator can help regrow sensory and motor neurons in the spinal cord when given to mice 12 weeks after severe injury.
The researchers used a small molecule called TTK21 to activate genetic programming that stimulates regeneration of axon (neuron fibers) in neurons. TTK21 alters the epigenetic status of genes by activating the CBP/p300 family of co-activator proteins. The team tested the TTK21 treatment in a mouse model of severe spinal cord injury. The mice lived in a rich environment that provided opportunities for physical activity, and human patients were encouraged.
Treatment was started 12 weeks after severe spinal cord injury and continued for 10 weeks. The researchers found many improvements after the TTK21 treatment compared to the control treatment. The most obvious effect was increased axon growth in the spinal cord. They also found that retraction of motor axons above the point of injury was halted, and growth of sensory axons increased. These changes are likely due to the observed increase in gene expression related to regeneration.
While this approach is still far from being tried in human patients, the researchers say their early results are encouraging. The next step would be to further enhance these effects and stimulate the regenerated axons to reconnect with the rest of the nervous system so that the animals can regain their ability to move easily.
Professor Di Giovanni commented: “This work shows that a drug called TTK21, when taken regularly once a week after chronic spinal cord injury (SCI) in animals, can promote neuronal regrowth and increase synapses needed for neuronal transmission.
“This is important because chronic spinal cord injury is an untreated condition in which neuronal regrowth and repair fails. We are now exploring the combination of this drug and strategies that bridge the spinal cord gap such as biomaterials as possible ways to improve disability in SCI patients.”
Reference: Muller P, Virgils FD, Kong Ji, et al. CBP/p300 activation enhances axon growth, proliferation, and synaptic plasticity in chronic experimental spinal cord injury with severe impairment. Plus Bio. 2022; 20(9): e3001310. dui: 10.1371 / journal.pbio.3001310
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