“Human and veterinary medicine are confronted with similar problems and employ similar means for their solution; and taken together, ..justify the contention that they are two branches of one medicine.”

Charnock Bradley D.Sc., M.R.C.V.S, 1927

Existing Challenges in Translational Research

Despite massive investments in drug discovery and preclinical research, >90% of therapeutics fail in clinical trials (Phase I through Phase III), with the majority (>70%) failing in Phase II (efficacy).1  A major root cause for these excessive failure rates are suboptimum laboratory animal models (LAMs) which have low phenotypic diversity, require disease induction and are studied under artificial conditions. Understandably, these suboptimal attributes have produced a long standing reproducibility crisis in translational research which is well acknowledged by the scientific community2, the National Institutes of Health 3,4 and the Food and Drug Administration.5  Based on these LAM failures, in 2022 the FDA Modernization Act 2.0 (Act) was passed, permitting in vitro models to replace the requirements for preclinical LAM studies.  The FDA and NIH are advocating for development of in vitro models despite no evidence they will yield any greater benefit than LAMs.  In reality, in vitro models are a further departure from living system and disease complexity so only time will tell if these in vitro models are predictive.

Veterinary Clinical Studies

Comparative Medicine: A far more rational approach would be to bridge the translational gap by evaluating animals which naturally develop comparative diseases to humans. Notably, companion animal dogs naturally develop >100 diseases with molecular, cellular, and physiological homology to humans;6-18 co-exist in the same environment; and receive near equivalent level of care to humans.  In turn, companion animal dogs largely mirror a human Phase II patient.

There is an increasing demand to leverage veterinary studies within the pharmaceutical industry to de-risk biomedical development. For example, Calviri is pioneering a novel neoantigen cancer vaccine in dogs which proposes to have applications in humans.  Another example is a Valley Fever vaccine being developed for veterinary patients (dogs) that may pave the way for a human vaccine.

Veterinary Clinical Studies

References

 

  1. BIO-Organization. New Clinical Development Success Rates 2011-2020 Report. 2021.
  2. Walker RL, Saylor, K.W., Waltz, M. et al. Translational science: a survey of US biomedical researchers’ perspectives and practices. Lab Animal. 2022;51:22-55.
  3. Austin CP. Translating translation. Nat Rev Drug Discov. 2018;17(7):455-456.
  4. Austin CP. Opportunities and challenges in translational science. Clin Transl Sci. 2021;14(5):1629-1647.
  5. Services UDoHaH. Advancing New Altnerative Methodologies at FDA. In: FDA, ed: US Department of Health and Human Services; 2021:34.
  6. Argyle DJ. The benefits of comparative medicine — a hundred years to come to our senses. Vet J. 2005;170(2):147-148.
  7. Barthelemy I, Hitte C, Tiret L. The Dog Model in the Spotlight: Legacy of a Trustful Cooperation. J Neuromuscul Dis. 2019;6(4):421-451.
  8. Mestrinho LA, Santos RR. Translational oncotargets for immunotherapy: From pet dogs to humans. Adv Drug Deliv Rev. 2021;172:296-313.
  9. Michell A. Only Comparative Medicine: the future of comparative medicine and clinical research. Res Vet Sci. 2000;69(2):101-106.
  10. Pallotti S, Piras IS, Marchegiani A, Cerquetella M, Napolioni V. Dog-human translational genomics: state of the art and genomic resources. J Appl Genet. 2022;63(4):703-716.
  11. Ruple A, MacLean E, Snyder-Mackler N, Creevy KE, Promislow D. Dog Models of Aging. Annu Rev Anim Biosci. 2022;10:419-439.
  12. Schiffman JD, Breen M. Comparative oncology: what dogs and other species can teach us about humans with cancer. Philos Trans R Soc Lond B Biol Sci. 2015;370(1673).
  13. Sebbag L, Mochel JP. An eye on the dog as the scientist’s best friend for translational research in ophthalmology: Focus on the ocular surface. Med Res Rev. 2020;40(6):2566-2604.
  14. Stroud C, Dmitriev I, Kashentseva E, et al. A One Health overview, facilitating advances in comparative medicine and translational research. Clin Transl Med. 2016;5(Suppl 1):26.
  15. Ambrosini YM, Borcherding D, Kanthasamy A, et al. The Gut-Brain Axis in Neurodegenerative Diseases and Relevance of the Canine Model: A Review. Front Aging Neurosci. 2019;11:130.
  16. Cummings BJ, Head E, Ruehl W, Milgram NW, Cotman CW. The canine as an animal model of human aging and dementia. Neurobiol Aging. 1996;17(2):259-268.
  17. Dewey CW, Davies ES, Xie H, Wakshlag JJ. Canine Cognitive Dysfunction: Pathophysiology, Diagnosis, and Treatment. Vet Clin North Am Small Anim Pract. 2019;49(3):477-499.
  18. Ruehl WW, Bruyette DS, DePaoli A, et al. Canine cognitive dysfunction as a model for human age-related cognitive decline, dementia and Alzheimer’s disease: clinical presentation, cognitive testing, pathology and response to 1-deprenyl therapy. Prog Brain Res. 1995;106:217-225.