Although psychedelic drugs may get all the attention when it comes to finding new ways to treat neuropathic pain, research in mice has suggested that a peptide approach could also be effective.
Use of a short lipid peptide (SLiP) developed by Mimetic Medicines disrupted a crucial interaction of voltage-gated sodium channels (Nav1.8) by reducing the number of these channels in the cell membrane in mice, according to research published October 6 in Cell Reports Medicine.
Nav1.8 channels are primarily expressed in sensory neurons of the dorsal root ganglion, located along the spinal cord. These neurons relay sensory information from the periphery of the body to the central nervous system (CNS) so that the brain can recognize the signal and decide how to act.
In neuropathic pain, these neurons are dysfunctional because they are in a state of hyperexcitability. This is characterized by an increase in Navs on the cell surface, which makes the cells overly sensitive and fire more easily, sending a constant pain signal to the CNS, the main symptom of neuropathic pain.
“Nav 1.8 still holds a lot of potential as a target for the treatment of chronic pain,” Rasheen Powell, Ph.D., Mimetic’s chief scientific officer, told Fierce in an interview. “This paper lays the groundwork for everyone to be able to say that we need to go beyond just allosteric inhibition of this channel, and that we need to understand these channels not just as static proteins in the membrane, but as actual proteins that move in and out of the membrane.”
In the study, researchers found that the scaffolding protein ankyrin-3 (Ank3) interacts with Nav1.8 to drive neuronal hyperexcitability and pain-triggering signals.
SLiPs are mimetics designed to “function as a bait molecule,” said Powell, who explained that the researchers wanted to test whether Mimetic’s SLiP was able to bind directly to Ank3 and surpass its binding potential to its desired target, Nav1.8.
“SLiP technology lends itself very well to modifications as well as different targets,” Powell said. “We are really confident that we will be able to tackle many different channelopathies and that this SLiP technology can extend beyond ion channels – we just need to show it.”
Massachusetts biotech Mimetic was founded in 2023 with a mission to explore the therapeutic potential of SLiPs. The SLiP used in this study serves as a “prototype for a class of different SLiPs,” Powell noted.
“This molecule has led to the development of several SLiP candidates that we are currently evaluating,” he added.
Common treatments for neuropathic pain include the gabapentinoid pregabalin and duloxetine, a serotonin and norepinephrine reuptake inhibitor. Vertex Pharmaceuticals already has an allosteric Nav1.8 inhibitor on the market for acute pain in the form of the non-opioid analgesic Journavx, but the biopharmaceutical company has not yet won approval for the drug to treat peripheral neuropathic pain.
Another hot area of research in the treatment of nerve pain is psychedelics, with a group at MD Anderson Cancer Center recently reporting the success of the magic mushroom extract, psilocybin, in reducing chemotherapy-induced peripheral neuropathy.
Gn Health
