The study of different animal models, such as salamanders, hydras or frogs, has given important clues about how regeneration works in other species and, although we are still far from being able to regenerate a limb, we could be closer to achieving it with nerve cells. . A team of scientists from University College London has identified a new compound that can stimulate nerve regeneration after injury, as well as protect heart tissue from the type of damage seen in a heart attack.
The study, published in Nature, identified a chemical compound, called 1938, that activates the phosphoinositide 3-kinase, or PI3K, signaling pathway and is involved in cell growth. The results of this initial research showed that the compound increased the growth of neurons in nerve cells and, in animal models, reduced heart tissue damage after major trauma and was also able to regenerate lost motor function in a model. of nerve injury.
Phosphoinositide 3-kinase (PI3K) is a type of enzyme that helps control cell growth. It is active in various situations, such as initiating wound healing, but its functions can also be hijacked by cancer cells to allow them to proliferate. As a result, cancer drugs have been developed that inhibit PI3K to restrict tumor growth. But the clinical potential of activating the PI3K pathway remains unexplored.
“Kinases are key ‘molecular machines’ for controlling the activities of our cells, and are targets for a wide range of drugs – explains Roger Williams, leader of the study, in a statement -. Our goal was to find activators of one of these machines “We found that we can directly activate a kinase with a small molecule to achieve therapeutic benefits by protecting the heart from injury and stimulating neuronal regeneration in animal studies.”
Although more research is needed to translate these findings into clinical practice, 1938 appears to be one of the few compounds in development that can reliably promote nerve regeneration. The 1938 administration during the first 15 minutes of blood flow restoration after a heart attack provided substantial tissue protection in a preclinical model. Usually, when blood flow is restored, areas of dead tissue form that can lead to heart problems later in life.
For its part, when 1938 was added to nerve cells grown in the laboratory, the growth of the neurons increased significantly. A rat model with a sciatic nerve injury was also tested, and administration of 1938 to the injured nerve resulted in increased recovery in the hindlimb muscle, indicating nerve regeneration.
The authors are currently working to develop new therapies that target peripheral nerve damage, such as occurs in severe hand and arm injuries. They are also exploring whether PI3K activators could be used to help treat damage to the central nervous system, for example due to spinal cord injury, stroke, or neurodegenerative disease.
“There are currently no approved drugs to regenerate nerves that can be damaged as a result of injury or disease, so there is a great unmet need,” concludes James Phillips, co-author of the study. Our results show that there is potential for drugs that activate PI3K to speed up nerve regeneration and, more importantly, localized delivery methods could prevent problems with unwanted effects that have caused other compounds to fail.”
