JNCASR researchers used a small molecule conjugated to carbon nanospheres to activate an enzyme (Cbp) that promotes axon regeneration and recovery after spinal cord injury. Regeneration and growth of axons led to recovery of sensory and motor functions in the animals with spinal cord injury. Mice could walk normally on the floor without limping and quickly sense and remove the adhesive stuck to the hindpaws indicating recovery.
Spinal cord injury can now be repaired using a small molecule (TTK21) synthesised by a team led by Prof. Tapas Kumar Kundu from the Molecular Biology and Genetics Unit at Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR), Bangalore, a study has found. The small molecule tested both on mice and rat models promoted regeneration and growth of new sensory and motor axons leading to recovery of sensory and motor functions in the animals with spinal cord injury.
This finding in animal models prompted the researchers to investigate the underlying molecular mechanism to identify a therapeutic target to achieve recovery after spinal injury. They found that post spinal cord injury, animals that were earlier exposed to different stimuli expressed changes in the Cbp enzyme–mediated acetylation. This change brought about by the enzyme caused an increase in the expression of a set of genes associated with regeneration and growth of axons.
“Mimicking the regenerative effect of environmental stimuli, we wanted to test if our small molecule could activate the Cbp enzyme and promote axon regeneration and recovery,” says Akash K. Singh, a PhD student at JNCASR and co-author of a paper published in the journal Science Translational Medicine.
In trials carried out in mice and rats, the small molecule injected four hours after the injury and once a week for five weeks resulted in regeneration and growth of axons at the site of injury. “The extent of regeneration and functional recovery of axons was nearly the same in both mice and rats. This proved our small molecule has a therapeutic effect,” says Dr. Sarmistha H. Sinha, post-doctoral fellow from JNCASR and co-author of the paper.
“Along with the Imperial College London, we are exploring the possibility of conducting pre-clinical trials and jointly develop the molecule for therapeutic use in humans,” Prof. Kundu says.