Cancer-related Neuropathy May Respond to Gene Therapy

Recent research using rats indicates that gene therapy might treat the neuropathic pain that affects 90% of patients with cancer. This pain arises from nerve damage caused by tumors, surgery, chemotherapy, and/or radiation.¹

In this study, researchers transferred the KCC2 gene into the spinal canal of rats, restoring the chloride levels that had become abnormal after nerve injury. In addition to holding promise for treating neuropathic pain from the development and treatment of cancer, this gene therapy holds potential for addressing pain from diabetic neuropathy and spinal cord injury as well. Neuropathic pain is associated with lowered activity levels of KCC2.

“We found that delivery of KCC2 produced a complete and long-lasting reversal of nerve injury-induced pain hypersensitivity by restoring chloride homeostasis,” said Hui-Lin Pan, MD, PhD, professor of anesthesiology and perioperative medicine, University of Texas M.D. Anderson Cancer Center, Houston, and study leader.

“This information significantly advances our understanding of these processes and provides a promising gene therapy strategy for treating unmanageable neuropathic pain.”

Proper chloride levels are essential for the function of nerve cells. Nerve damage, such as that accrued during surgery or as a toxic side effect of chemotherapy, disrupts the balance of chloride levels, causing inhibitory neurotransmitters GABA and glycine to be less effective. When GABA and glycine are less effective, the activity of excitatory nerve receptors, called NMDA receptors, increases.

“Diminished synaptic inhibition by GABA and glycine and increased NMDA receptor activity are two key mechanisms underlying neuropathic pain,” said Pan.

“However the reciprocal relationship between the two is unclear. By using KCC2 gene transfer, we were able to restore chloride balance, which also unexpectedly normalized NMDA receptor activity increased by nerve injury.”