The main reason that the outlook for recovery in those with spinal cord injuries is often poor is because damaged nerve cells within this region don’t regenerate. Scientists are therefore endeavoring to develop therapies that promote nerve cell regrowth at the site of injury, but few have offered much hope so far. Now, scientists may have some promising candidates on their hands with the discovery that a class of FDA approved anticancer drugs not only boosted cell regeneration in rodents with spinal cord injuries, but they also improved the animals’ motor skills, such as walking. The study has been published in Science.
Unlike nerve cells in other areas of the body, such as the limbs and torso, those in the central nervous system (brain and spinal cord) fail to regenerate after injury. Although scientists do not fully understand why, it is believed to be a consequence of several different factors, including the formation of scar tissue and the presence of various inhibitory factors that prevent the nerve cell’s long stringy projection, called an axon, from regrowing. If the axon can’t repair itself, the flow of information between nerves is interrupted, which is why many with spinal cord injuries suffer disabilities or paralysis.
Recently, lab studies demonstrated that it is possible to promote axon regeneration using a combination of drugs and interventions that ultimately result in stabilization of the rigid, hollow rods within cells known as microtubules. These structures, which are constantly growing and shrinking, perform a variety of cellular functions, including providing mechanical support, determining cell shape and assisting cell movement. Unfortunately, the fact that so many different treatments were required, some of which can’t reach the brain, meant that translating this as a valid clinical therapy would be exceedingly difficult.
Armed with the knowledge that it is indeed possible to boost axon regeneration, an international team of scientists, led by researchers at the German Center for Neurodegenerative Diseases, aimed to find a way to achieve this outcome but with a clinically feasible technique. They decided to investigate the potential of a class of FDA-approved anticancer drugs called epothilones, which are not only capable of reaching the brain, but also act to stabilize microtubules.
The researchers therefore administered one of these drugs, called epitholone B, to rats with spinal cord injuries and monitored their progress. They found that those treated with epothilone B showed a significant reduction in scar tissue at the site of trauma, which is important since this tissue contains axon growth inhibitory factors. They discovered that this was the result of the drug inhibiting the microtubules from forming within the scar tissue-producing cells, which prevented them from migrating towards the injury site. Concomitantly, epothilone B also promoted microtubule extension within the tips of nerve cell axons, which propelled their growth and thus assisted their regeneration.
Of course, these effects are fairly meaningless if a clinical improvement is not observed, so the researchers investigated whether the drug also benefitted their motor function. Using a clinically relevant spinal cord injury model, the researchers found that epothilone B improved both walking balance and coordination in the animals, which is promising. The researchers would therefore like to continue their work by investigating the drug’s efficacy in different types of injury.