Novel peptide approach reduces chronic neuropathic pain in mice

New results published today in Cell Reports Medicine help explain why. Previous drug development strategies for targeting Na_V 1.8 focused on reducing the channel's ability to open properly. Researchers have now discovered that Na_V 1.8 activity in neurons relies on an interaction with a scaffolding protein called ankyrin-G (Ank3) to maintain the heightened electrical activity in pain-triggering neurons during pathological pain. They found that disrupting that interaction with a short lipidated peptide (SLiP) reduces the levels of Na_V 1.8 in the cell membrane, quieting hyperexcitable pain-triggering neurons, and reducing pain-like behaviors in mouse models, while sparing acute protective pain.

Boston Children's has licensed the intellectual property arising from this work to Mimetic Medicines, a Boston-based biotechnology company developing novel therapeutics based on this mechanism. Mimetic Medicines has taken the original academic discovery forward by developing investigational long-acting SLiP candidates designed to disrupt the Nav1.8–Ank3 interaction systemically. Their goal is to produce a non-opioid treatment for chronic neuropathic pain that selectively suppresses pathological pain signaling rather than normal sensory function. Rasheen Powell, a former postdoc in the Woolf lab, is the Chief Scientific Officer of Mimetic Medicines.

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Boston Children's Hospital

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