▎Editor of WuXi AppTec content team

Spinal cord injury is an irreversible neurological injury that causes many inconveniences
to the patient's daily life.

At present, there is still no effective treatment for patients with severe spinal cord injury, and physical rehabilitation therapy can help some patients restore partial mobility, but for cases of severe spinal cord injury, the effect of physical rehabilitation therapy is very limited
for these patients because spinal cord neurons cannot regenerate after injury.

Recently, scientists at Imperial College London found that after 12 weeks of severe spinal cord injury, weekly treatment with an epigenetic activator can promote the regrowth of sensory and motor neurons in the spinal cord, which was published in the academic journal PLOS Biology
.

In this study, a small molecule called TTK21 can induce genetic reprogramming of axonal regeneration in neurons, and TTK21 alters the epigenetic state
of genes by activating the co-activator CBP/p300.

Subsequently, the team tested the therapeutic effects
of TTK21 in mouse models with severe spinal cord injury.

These mice have a privileged living environment and are well equipped for physical activity, as we advocate for rehabilitation in human spinal cord injury patients
.

TTK21 treatment began 12 weeks after severe spinal cord injury and lasted a total of 10 weeks
.

The researchers found that the TTK21 treatment resulted in significant improvements
in spinal cord neuron status in mice compared to the control group.

The most pronounced change is an increase
in axons in the spinal cord.

They also found that motor neuron axons located above the point of injury stopped contracting and that the growth of sensory neuron axons increased, and the researchers believe these changes were due to increased gene expression associated with axon regeneration
.

In its natural state, axons do not have the ability to regenerate, and if damaged, the growth vertebrae responsible for promoting axonal growth disintegrate, and this study shows that the regeneration of neuronal axons can be achieved through epigenetic intervention in genes involved in cell regeneration
.

This work builds on the team's previous research, which previously found that TTK21 treatment immediately after injury in mice or rats with moderate spinal cord injury improved mouse function, and that TTK21 treatment was able to upregulate the expression of PCAF genes and increase the regeneration
of axonal fibers.

If supplemented with exercise, these treatments are more effective, similar to the situation of human physical therapy
.

In this study, the researchers attempted to reproduce previous trial results
in mice with chronic, severe spinal cord injury.

Image source: 123RF

However, unlike previous results in rodents with moderate spinal cord injury, mice with severe spinal cord injury in this study did not see much improvement in their ability to walk after treatment with TTK21, suggesting that TTK21 was not sufficient to improve overall activity
of the nervous system.

Nonetheless, the neuronal axonal changes observed in this study, fiber growth within the dorsal root ganglia, and genetic changes associated with these processes provide us with more clues to further our understanding of the mechanisms associated with spinal cord injury recovery, laying the groundwork
for the development of new therapies.

TTK21 is still a long way from human application, but these findings are very encouraging and bring new hope for the treatment of spinal cord injuries in
the future.

The team's next research plan is to explore how to further enhance the neuronal changes brought about by TTK21, prompting regenerated axons to reconnect with other parts of the nervous system, so that spinal cord-damaged animals can regain the ability to
move at will.

At the same time, the team intends to explore combining this small molecule with strategies to bridge the gaps in the spinal cord, such as biomaterials, to provide more treatment options
for patients with spinal cord injuries.

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