Research & Development Epigenetic Treatment Stimulates Spinal Cord Regeneration in Mice

Epigenetic Treatment Stimulates Spinal Cord Regeneration in Mice

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A research group led by scientists from Imperial College London has found success in promoting axon fiber regeneration in mice with major spinal cord injuries.

Even though the rodents weren’t able to improve their walking – in contrast to earlier experiments using the same molecule at a different time and mice with less serious SCI – it’s still a significant step toward comprehending and possibly designing treatments for patients with calamitous injuries.

Physical therapy can often help partially cure many mild and moderate spinal cord injuries, but the best way to treat more critical cases has so far eluded medical professionals. The main challenge is in reattaching the axon fibers – the nerve cells that transmit signals from the brain and move through the spinal cord  – below and above the point of the injury. The growth cones, which are the components of the cells that promote growth, disintegrate if the axon fibers are damaged in any way. The spinal cord cannot function normally due to this. 

The research team had been searching for other methods to promote axon fiber growth, since this was the only practical way to make progress in this case. One possible approach in this regard is to induce epigenetic modifications to genes involved in cell regeneration. The team used TTK21, a tiny-molecule epigenetic activator, to enhance numerous aspects of spinal axon growth in mice with acute SCI.

To be able to effectively use TTK21, the team needed to look back on previous use cases. Many older studies suggested that TTK21 improves the expression of PCAF regeneration genes, thereby enhancing axon fiber regeneration. They did point out that rats with reasonable spinal cord injuries needed to receive the activator six to twelve hours after the injury was sustained.

The researchers had also earlier noted that to make the most of the ambitious treatment and improve the chances of recovery, the mice needed to be kept in a refined environment – ideally, one with big cages, running wheels and other toys they might enjoy.

The aim this time around was to understand the effectiveness of TTK21 in mice with severe SCI instead of just mild or moderate. For this, the team injected TTK21 into a group of mice suffering from chronic SCI on a weekly basis for ten weeks. The experiment began 12 weeks after the mice had sustained the injuries. The researchers ensured that both groups of mice – control and experimental – were kept in the healthiest environment possible.

Although the mice couldn’t walk better, they showed new growth of motor axon fibers. The fact that sensory growth increased at all is a big triumph, according to Simone Di Giovanni, Head of the Neuroscience Division at Imperial College. He said, “This work shows that a drug called TTK21, when administered systemically once/week after a chronic spinal cord injury (SCI) in animals, can promote neuronal regrowth and an increase in synapses that are needed for neuronal transmission.” 

The researchers expressed optimism about what these findings mean for human patients, despite the fact that the approach is still far from being tested on them.

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