A research team from the German Centre for Neurodegenerative Diseases (DZNE) made a breakthrough that can potentially lead to more effective treatments for paralysis and other spinal cord-related injuries.
The study stemmed from the common belief that when we reach adulthood and our bodies have been fully formed, our neurons (also known as nerve cells) stop growing. In terms of injuries that affect the brain and the spinal cord — when cells of the central nervous system get damaged, the neuron connectors called axons may get severed. When this happens, the axons are no longer able to grow back, the nerve cells can no longer transmit electrical impulses to the brain, and this leads to paralysis.
This is what we know happens; what we don’t know is what prompts the severing. And this is the main question that the DZNE team led by Frank Bradke struggled to find an answer for.
Based on their hypothesis that there is some kind of ‘molecular brake’ that stops the growth of neurons, using mice as their test subjects, the team went on to search if such gene did exist. It could have been an impossible search due to the large number of genes present in the body. But with the help of bioinformatics — using computers to analyse and interpret biological data — the team was able to narrow down their search to a ‘promising candidate’.
The gene is known as Cacna2d2 and it is believed to play a role in regulating the flow of calcium particles into cells, which in turn affects communication between nerve cells. As Bradke said, “This gene…plays an important role in synapse formation and function, in other words in bridging the final gap between nerve cells.”
To test if Cacna2d2 was indeed the gene that functioned as the body’s ‘molecular brake’, the team tried to reactivate it by administering a drug called Pregabalin (PGB) — known for its calcium channel binding and pain relieving effects on damaged nerves — to mice with spinal cord injuries. After the PGB was given, the researchers noticed that new nerve connections began to grow in the mice. Conversely, by deactivating the gene, the team was able to validate that it indeed affected nerve fiber regeneration.
According to Bradke, the study showed that “synapse formation acts as a powerful switch that restrains axonal growth. A clinically-relevant drug can manipulate this effect.” In other words, a drug such as PGB may have regenerative effects if it is given in time. And in the long run, it may even lead to the development of new or better treatment options.
Everything is still speculative at this point, especially when considering human clinical trials are still a long way off. But just like with other discoveries, sometimes the first step is all that’s needed. Who knows, perhaps, and if that step is the right one, it could lead us to a feasible treatment for paralysis together with other neurodegenerative diseases.
The research was published on October 19, 2016 in Neuron.