Value Proposition:
· First Non-Surgical Therapy for Schwannomatosis Pain: Introduces the first targeted, injectable, mechanism-based treatment for schwannoma-associated pain, replacing the current reliance on tumor resection for pain control.
· Mechanosensitive Ion Channel (MSC) Inhibition: GsMTx-4 uniquely blocks mechanosensitive ion channels (Piezo1, Piezo2, TRPV4) by membrane-mediated gating inhibition rather than direct channel binding.
· Prevents and Reverses Tumor-Induced Hyperalgesia: Demonstrated both prophylactic and reversal efficacy in validated chronic schwannomatosis pain mouse models.
· Local, Minimally Invasive Therapy: Designed for focal peritumoral injection, enabling precision pain control without systemic exposure.
· Non-Toxic, Non-Immunogenic Peptide: Biologically stable, enzymatically resistant, and previously evaluated for safety in additional disease models.
· Broad Mechanotransduction Platform Potential: Applicable beyond schwannomatosis to other mechanically driven neuropathic pain and compressive tumor pain syndromes.
Unmet Need:
Schwannomatosis is a rare genetic tumor disorder with an incidence of approximately 1 in 40,000, characterized by multiple painful schwannomas along peripheral nerves. Patients suffer from severe neuropathic, nociceptive, and inflammatory pain - often triggered by light touch or tumor palpation. At present, surgical resection is the only effective pain treatment, yet most patients develop multiple tumors over time, making repeat surgery medically and logistically untenable. There are no FDA-approved pharmacologic therapies for schwannomatosis tumor pain. GsMTx-4 directly addresses this critical therapeutic gap by offering a non-surgical, locally injected, disease-mechanism-targeted analgesic solution.
Technology Description:
This technology utilizes GsMTx-4, a cysteine-knot peptide derived from Grammostola spatulata spider venom, as a potent inhibitor of mechanosensitive ion channels (MSCs) responsible for pressure-induced pain signaling. Schwannoma tumor cells secrete pro-inflammatory factors that chemically sensitize peripheral sensory neurons while simultaneously inducing mechanical nerve compression. This dual inflammatory-mechanical mechanism generates persistent hyperalgesia.
In multiple in vivo mouse models using conditioned media from human painful schwannomas, GsMTx-4 completely prevents and reverses mechanical hypersensitivity. Local co-injection with tumor-conditioned media restores paw-withdrawal thresholds to baseline and reverses established chronic primed pain states. The peptide embeds within strained lipid bilayers and physically prevents MSC gating without off-target ion channel inhibition.
Key scientific features include:
· Membrane-mediated mechanotransduction blockade
· Selective inhibition of stretch-activated pain signaling
· Reversal of both acute and chronic pain sensitization
· Validated efficacy in two-hit chronic hyperalgesic priming models
Clinical Validation and Stage of Development:
Extensive in vivo mouse validation demonstrates robust prevention and reversal of schwannoma-related pain using local GsMTx-4 injection, including long-term suppression of chronic primed hyperalgesia lasting weeks. Prior toxicology, biodistribution, tissue accumulation, and clearance studies have already been performed in muscular dystrophy and myocardial infarction models by external collaborators. The technology is now positioned for IND-enabling toxicology and formulation development for first-in-human localized injection studies.
Data Availability:
· Comprehensive in vivo pain reversal data available
· Available upon request
Patent Status:
GsMTx-4 as a Treatment of Schwannomatosis Induced Pain
U.S. Patent Application P19032-01
Current Status: Unfiled (as of 8/14/2025)
Select Publications:
Carson Gutierrez, Randy Rubright, and Kimberly Laskie Ostrow. "GsMTx-4 Reduces Mechanical Allodynia in a Model of Schwannomatosis-related Pain." The Journal of Pain (2025): 105597.
