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“Epigenetic therapy supports spinal cord regeneration in mice”
Currently, spinal cord injuries have no effective treatment. Physical rehabilitation can help patients regain some mobility but, for severe cases, results are extremely limited by the inability of neurons in the spine to regenerate naturally after injury.
However, new research conducted by Professor Simone Di Giovanni and published in the journal PLOS Biology shows that weekly treatments with an epigenetic activator can promote the regrowth of 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 induces the regeneration of axons (nerve fibers) in neurons. TTK21 alters the epigenetic state 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 an enriched environment that gave them the opportunity to be physically active, as is encouraged in human patients.
Treatment started 12 weeks after severe spinal cord injury and lasted 10 weeks. The researchers found several improvements after the TTK21 treatment compared to the control treatment. The most notable effect was greater sprouting of axons in the spinal cord. They also found that the retraction of motor axons above the point of injury stopped and the growth of sensory axons increased. These changes were likely due to the observed increase in regeneration-related gene expression.
Although the approach is still far from being tested on human patients, the researchers say their initial findings are encouraging. The next step will be to further enhance these effects and induce the regenerating axons to reconnect to 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 administered systemically once a week after chronic spinal cord injury (SCI) in animals, can promote neuronal regeneration. and an increase in synapses necessary for neuronal transmission.
“This is important because chronic spinal cord injury is an incurable condition where neural regeneration and repair fail. We are currently exploring the combination of this drug with strategies that bridge the spinal cord gap, such as biomaterials, as possible avenues to improve disability in patients with IBS.
Reference: Muller F, Virgilis FD, Kong G, et al. CBP/p300 activation promotes axon growth, sprouting, and synaptic plasticity in experimental chronic spinal cord injury with severe disability. Organic PLOS. 2022;20(9):e3001310. doi:10.1371/journal.pbio.3001310
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