Researchers showed that blocking the dual leucine zipper kinase (DLK) gene inhibits degeneration of ailing nerve cell branches, possibly preventing neuropathy. The condition is a side effect of some forms of chemotherapy and can also afflict patients with cancer, diabetes, kidney failure, viral infections, neurodegenerative disorders and other ailments.
"Neuropathy can become so extraordinarily painful that some patients stop taking their chemotherapy, regardless of the consequences in their fight against cancer," says co-senior author Aaron DiAntonio. "So we are very excited about the possibilities this gene may offer for reducing that pain."
Scientists have known since 1850 that nerve cells have ways to prune branches (also known as axons) that are injured. Although axon pruning is also a normal part of early human development, inappropriate loss of axons in the adult nervous system causes painful sensations that have been compared to burning, freezing or electric shock and have come to be known as neuropathy.
The researchers showed that the long axons of the sciatic nerve in mice with a mutated DLK gene resisted degeneration after it was surgically cut. In follow-up tests, the researchers took nerve cells in culture and treated their axons with the chemotherapy drug vincristine. Normal axons degenerated rapidly after exposure to the drug, but axons where DLK's activity had been blocked were protected from degeneration. DLK appears to act like a contractor that calls in wrecking crews, DiAntonio notes. It helps make the decision to eradicate an axon, but the actual demolition is left to other processes called up by DLK.
"The pain of neuropathy is often a key factor that limits the dose in cancer chemotherapy," DiAntonio notes. "We know when patients are going to start their treatment, so one day it might be possible to start patients on a DLK-blocking drug before their chemotherapy and spare them considerable pain."
MEDICA.de; Source: Washington University School of Medicine