The National Institute of Health estimates that 100 million Americans, or around a third of the US population, live with a chronic pain condition. While the economic burden, more than US$500 billion annually, is well documented, increasingly studied is its wide-ranging impact on mental health and the growth in opioid addiction.
As such, scientists are eager to develop effective non-opioid, gene-based ways to disrupt the pain signaling experienced in chronic conditions, in the hope that it can vastly improve one’s quality of life without any negative side effects.
The latest promising discovery comes out of the New York University (NYU) College of Dentistry’s Pain Research Center, which has developed a novel targeted therapy to alleviate pain delivered by an engineered virus.
“There is a significant need for new pain treatments, including for cancer patients with chemotherapy-induced neuropathy,” said Rajeesh Khan, director of the center and professor of molecular pathobiology at NYU Dentistry. “Our long-term goal is to develop a gene therapy that patients could receive to better treat these painful conditions and improve their quality of life.”
What makes their findings different is that it indirectly targets the NaV1.7 sodium channel, which is is found at the end of pain-detecting nerves, and has been the focus of a lot of research into tackling chronic pain so far. Instead of trying to block the sodium channel, in order to disrupt messages along those pain nerves, the scientists indirectly regulated it with a protein known as CRMP2.
“Our study represents a major step forward in understanding the underlying biology of the NaV1.7 sodium ion channel, which can be harnessed to provide relief from chronic pain,” said Khanna. “CRMP2 ‘talks’ to the sodium ion channel and modulates its activity, allowing more or less sodium into the channel.
“If you block the conversation between Nav1.7 and CRMP2 by inhibiting the interaction between the two, we can dial down how much sodium comes in,” he added. “This quiets down the neuron and pain is mitigated.”
The researchers found the region within the NaV1.7 channel where CRMP2 binds to it to regulate its activity. Interestingly, the protein didn’t bond to other sodium ion channels, suggesting it has a unique ability to disrupt this pathway for therapeutic uses.
“This got us really excited, because if we took out that particular piece of the NaV1.7 channel, the regulation by CRMP2 was lost,” said Khanna.
In an animal study, the scientists created a peptide from the channel corresponding to that binding region and inserted it into an adeno-associated virus to deliver it to neurons, where it would disrupt NaV1.7 function.
When the engineered virus was given to mice with chronic pain, such as sensitivity to touch, heat or cold, and peripheral neuropathy from chemotherapy, it took between a week and 10 days for the animals’ pain to be reversed.
They also gauged its inhibiting abilities on the cells of primates and humans. The team cautions more work is needed, but they believe the success of their research will translate into a therapy for humans.
“We found a way to take an engineered virus – containing a small piece of genetic material from a protein that all of us have – and infect neurons to effectively treat pain,” said Khanna. “We are at the precipice of a major moment in gene therapy, and this new application in chronic pain is only the latest example.”
The study was published in the journal Proceedings of the Natural Academy of Sciences (PNAS).
Source: New York University