Protective effect of a mitochondria-targeting peptide against paclitaxel-induced peripheral neuropathy

Chem Biol Drug Des. 2023 Apr;101(4):1012-1018. doi: 10.1111/cbdd.14192. Epub 2022 Dec 23.

Abstract

Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect of several anticancer agents including paclitaxel, a chemotherapeutic drug widely used in cancer treatment. CIPN deteriorates patients' quality of life and compromises cancer treatment. Dysfunction or injury of mitochondria has been suggested to be involved in the induction of this neuropathy. SS-20 is a tetrapeptide that targets mitochondria and restores mitochondrial bioenergetics. This study was aimed to examine the protective effect of SS-20 against paclitaxel-induced peripheral neuropathy using a murine model. Repeated administration of paclitaxel to mice induced peripheral neuropathy as demonstrated by the presence of mechanical allodynia and the loss of intraepidermal nerve fibers in the hind paw. Concomitant administration of SS-20 protected against the development of the neuropathy. Our results suggest that SS-20 may be a drug candidate for the prevention of CIPN.

Keywords: chemotherapy-induced peripheral neuropathy; mitochondria; neuropathic; paclitaxel; pain; painchemotherapy.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Letter

MeSH terms

  • Animals
  • Antineoplastic Agents* / pharmacology
  • Hyperalgesia / chemically induced
  • Mice
  • Mitochondria
  • Paclitaxel / pharmacology
  • Peptides / pharmacology
  • Peripheral Nervous System Diseases* / chemically induced
  • Peripheral Nervous System Diseases* / drug therapy
  • Peripheral Nervous System Diseases* / prevention & control
  • Quality of Life

Substances

  • Paclitaxel
  • Antineoplastic Agents
  • Peptides