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.