Preclinical characterization of the efficacy and safety of biologic N‑001 as a novel pain analgesic for post‑operative acute pain treatment

Authors

• Derek Allen, Neurocarrus Inc, University of California-Santa Cruz, University of Nebraska-Lincoln
• Samerender Nagam Hanumantharao, Neurocarrus Inc
• Rylie McDonell, University of Nebraska-Lincoln
• Karen‑Amanda Irvine, Stanford University School of Medicine
• Peyman Sahbaie, Stanford University School of Medicine
• David Clark, Stanford University School of Medicine, VA Palo Alto Health Care
• Paul H. Blum, Neurocarrus Inc, University of California-Santa Cruz, University of Nebraska-LincolnFollow

Document Type

Article

Date of this Version

7-21-2023

Citation

Scientific Reports | (2023) 13:11778 | https://doi.org/10.1038/s41598-023-38618-4

Comments

Open access.

Abstract

Inhibition of actin remodeling in nerves modulates action potential propagation and therefore could be used to treat acute pain. N-001 is a novel protein analgesic engineered from several C. Botulinum toxins. N-001 targets sensory neurons through ganglioside GT1b binding and ADP-ribosylates G-actin reducing actin remodeling. The activity and efficacy of N-001 was evaluated previously in vitro and in a mouse inflammatory pain model. To assess the relevance of N-001 for treatment of acute post-surgical pain, the current study evaluated the efficacy of N-001 in a mouse hind-paw incision model by periincisional and popliteal nerve block administration combined with mechanical testing. N-001 provided relief of pain-like behavior over 3 days and 2 days longer than the conventional long-acting anesthetic bupivacaine. Preclinical safety studies of N-001 indicated the drug produced no toxic or adverse immunological reactions over multiple doses in mice. These results combined with past targeting results encourage further investigation of N-001 as an analgesic for post-operative pain management with the potential to function as a differential nociceptor-specific nerve block.