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The Role of Pharmacogenomics in Rare Diseases

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Abstract

Rare diseases have become an increasingly important public health priority due to their collective prevalence and often life-threatening nature. Incentive programs, such as the Orphan Drug Act have been introduced to increase the development of rare disease therapeutics. While the approval of these therapeutics requires supportive data from stringent pre-market studies, these data lack the ability to describe the causes of treatment response heterogeneity, leading to medications often being more harmful or less effective than predicted. If a Goal Line were to be used to describe the multifactorial continuum of phenotypic variations occurring in response to a medication, the ‘Goal Posts’, or the two defining points of this continuum, would be (1) Super-Response, or an extraordinary therapeutic effect; and (2) Serious Harm. Investigation of the pharmacogenomics behind these two extreme phenotypes can potentially lead to the development of new therapeutics, help inform rational use criteria in drug policy, and improve the understanding of underlying disease pathophysiology. In the context of rare diseases where cohort sizes are smaller than ideal, ‘small data’ and ‘big data’ approaches to data collection and analysis should be combined to produce the most robust results. This paper presents the importance of studying drug response in parallel to other research initiatives in rare diseases, as well as the need for international collaboration in the area of rare disease pharmacogenomics.

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Authors and Affiliations

  1. BC Children’s Hospital Research Institute, 950 West 28th Avenue, Vancouver, BC, V5Z 4H4, Canada

    Alice Man, Colin J. D. Ross & Bruce C. Carleton

  2. Division of Translational Therapeutics, Department of Pediatrics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Alice Man, Gabriella S. S. Groeneweg & Bruce C. Carleton

  3. Michael G. DeGroote School of Medicine, McMaster University, Hamilton, ON, Canada

    Alice Man

  4. Pharmaceutical Outcomes Programme, British Columbia Children’s Hospital, Vancouver, BC, Canada

    Gabriella S. S. Groeneweg & Bruce C. Carleton

  5. Department of Medical Genetics, Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada

    Colin J. D. Ross & Bruce C. Carleton

  6. Faculty of Pharmaceutical Sciences, University of British Columbia, Vancouver, BC, Canada

    Colin J. D. Ross

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Bruce C. Carleton and Colin J.D. Ross receive federal grant funds from the Canadian Institutes of Health Research, Genome Canada, and Genome BC, with additional support provided by the British Columbia Provincial Health Services Authority, BC Children's Hospital Foundation, and Health Canada. They have also previously received research funding from Dynacare Next Specialized Diagnostics as part of a Genome Canada federal grant. Gabriella S.S. Groeneweg provides program management of these research funds. Bruce C. Carleton also receives federal grant funds from the US Centers for Disease Control and Prevention, and in the past 3 years has provided consultation services to the Canadian Agency for Drugs and Technologies in Health and Dynacare. Alice Man declares no conflicts of interest.

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AM contributed to the conceptualization, literature search, and writing of the original draft. BCC played a supervisory role and contributed to the conceptualization and writing of the original draft. AM, BCC, CJDR, and GSSG contributed to the review and editing of the manuscript. All authors read and approved the final manuscript.

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Man, A., Groeneweg, G.S.S., Ross, C.J.D. et al. The Role of Pharmacogenomics in Rare Diseases. Drug Saf (2024). https://doi.org/10.1007/s40264-024-01416-6

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