Safety of TCMCB07, a melanocortin-4 antagonist peptide, in dogs with naturally occurring cachexia

J Vet Intern Med. 2023 Nov-Dec;37(6):2344-2355. doi: 10.1111/jvim.16915. Epub 2023 Oct 28.

Abstract

Background: The melanocortin 4 antagonist TCMCB07 is safe and effective in reversing cachexia caused by sepsis or cancer in rodents. The safety and pharmacokinetics of TCMCB07 are demonstrated in healthy beagle dogs.

Hypothesis/objectives: The objectives of this study were to investigate the safety, peak plasma concentrations, and potential for efficacy of TCMCB07 in pet dogs with naturally occurring cachexia over a 4-week time period.

Animals: Fourteen dogs with cachexia of any underlying cause, except cancer of the oral cavity or gastrointestinal tract, were eligible for enrollment with informed client consent.

Methods: This study was a prospective, 1-armed open-label trial. Physical examination, complete blood count, chemistry panel, and owner-assessed quality of life surveys were checked at weeks 1, 2, and 4. Due to potential for bradycardia and hypotension, Holter monitoring and blood pressure evaluations were scheduled at pre-enrollment and week 4.

Results: Fourteen dogs completed the trial. Significant changes detected included increased mean body weight (18.6-19.5 kg, P < .02), increased body condition score (median Tufts 5-point thin dog scale score P < .004 and WSAVA muscle condition score P < .02) and increased mean blood urea nitrogen (21.79-30.43 mg dL-1 , P < .004). On quality of life surveys, pet owners perceived their dog appeared to be panting less (P < .002) and that the general health improved (P < .03). Four dogs had a change in coat pigmentation. The peak plasma concentration of TCMCB07 in cachectic dogs was similar to that in healthy beagle dogs.

Conclusions and clinical importance: TCMCB07 was safe and has potential efficacy in pet dogs with cachexia.

Keywords: anorexia; canine; emaciation; metabolism; therapy.

MeSH terms

  • Animals
  • Cachexia / drug therapy
  • Cachexia / veterinary
  • Dog Diseases* / drug therapy
  • Dogs
  • Humans
  • Melanocortins
  • Neoplasms* / veterinary
  • Peptides
  • Prospective Studies
  • Quality of Life

Substances

  • Melanocortins
  • Peptides