Epigenetic therapy in mice improves spine

Image: Shown is an increased density of synapses (green) contacting motoneurons (purple) in the spinal cord of an injured animal after treatment with the small molecule TTK21 – these are important for motor function.
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Credit: Franziska Mueller (CC-BY 4.0,

Currently, there is no effective treatment for spinal cord injury. Physical rehabilitation can help patients regain some mobility, but in severe cases the results are very limited because the nerve cells in the spine fail to regenerate normally after an injury. However, in a study published on September 20The tenth In the open access journal Biology PlusResearchers led by Simone Di Giovanni at Imperial College London in the UK show that weekly treatments with an epigenetic stimulant can help regrow sensory and motor neurons in the spinal cord when given to mice 12 weeks after severe injury.

Building on their previous success, the researchers used a small molecule called TTK21 to activate genetic programming that stimulates regeneration of axons in neurons. TTK21 alters the epigenetic status of genes by activating the CBP/p300 family of co-activator proteins. They tested 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. The next step would be to enhance these effects further and stimulate the regenerated axons to reconnect with the rest of the nervous system so that the animals can easily regain their ability to move.

Di Giovanni adds: “This work shows that a drug called TTK21 taken regularly once a week after chronic spinal cord injury (SCI) in animals can promote the regrowth of neurons and increase the synapses needed for neuronal transmission. This is important because injury Chronic spinal cord is an untreated condition where neuronal regrowth and repair fail. We are now exploring the combination of this drug with spinal cord gap-bridging strategies such as biomaterials as possible ways to improve disability in SCI patients.”


In your coverage, please use this URL to provide access to freely available paper in . format Biology Plus:

the quote: Muller F, de Vergilis F, Kong G, Cho L, Serger E, Chadwick J, et al. (2022) CBP/p300 activation enhances axon growth, sprouting, and synaptic plasticity in chronic experimental spinal cord injury with severe impairment. Plus Biol 20 (9): e3001310.

Author countries: United Kingdom, India

Financing: Translated ISRT Award – P90397 to SDG Marina Romoli Onlus-P82836 to SDG Rosetrees Trust-P72986 to SDG Brain Research Trust-P73576 to SDG. .

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