Drug repositioning for orphan diseases
Open accessAbstract
The need and opportunity to discover therapeutics for rare or orphan diseases are enormous. Due to limited prevalence and/or commercial potential, of the approximately 6000 orphan diseases (defined by the FDA Orphan Drug Act as <200 000 US prevalence), only a small fraction (5%) is of interest to the biopharmaceutical industry. The fact that drug development is complicated, time-consuming and expensive with extremely low success rates only adds to the low rate of therapeutics available for orphan diseases. An alternative and efficient strategy to boost the discovery of orphan disease therapeutics is to find connections between an existing drug product and orphan disease. Drug Repositioning or Drug Repurposing--finding a new indication for a drug--is one way to maximize the potential of a drug. The advantages of this approach are manifold, but rational drug repositioning for orphan diseases is not trivial and poses several formidable challenges--pharmacologically and computationally. Most of the repositioned drugs currently in the market are the result of serendipity. One reason the connection between drug candidates and their potential new applications are not identified in an earlier or more systematic fashion is that the underlying mechanism 'connecting' them is either very intricate and unknown or indirect or dispersed and buried in an ever-increasing sea of information, much of which is emerging only recently and therefore is not well organized. In this study, we will review some of these issues and the current methodologies adopted or proposed to overcome them and translate chemical and biological discoveries into safe and effective orphan disease therapeutics.
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Most repurposed drugs are the result of serendipity, either observed through off-label prescriptions written by clinicians or discovered through patient experience.
“However, most repurposed drugs are the result of serendipity7,8—either observed through off-label prescriptions written by clinicians, as with gabapentin and bupropion8, or discovered through patient experience, as with sildenafil6.”
From A foundation model for clinician-centered drug repurposing (2024) · cites this paper as [7]
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A foundation model for clinician-centered drug repurposing
Huang, K., Chandak, P., Wang, Q., Havaldar, S., Vaid, A., Leskovec, J., Nadkarni, G. N., Glicksberg, B. S., Gehlenborg, N., & Zitnik, M. (2024) · Nature Medicine · doi:10.1038/s41591-024-03233-x · Cited by 249 · see citing works
“To facilitate model interpretation, TxGNN’s Explainer module offers transparent insights into multi-hop medical knowledge paths that form TxGNN’s predictive rationales.”
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- Authors
- Sardana, D., Zhu, C., Zhang, M., Gudivada, R. C., Yang, L., & Jegga, A. G.
- Affiliations
- University of Cincinnati (US)
- Cincinnati Children's Hospital Medical Center (US)
- Venue
- Briefings in Bioinformatics
- Publisher
- Oxford University Press (OUP)
- Published
- 2011-04-18
- Volume
- 12
- Issue
- 4
- Pages
- 346-356
- ISSN
- 1467-5463 (ISSN-L)
- 1477-4054
- OpenAlex
- W2145321215
- Cited by
- 228
- References
- 59
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 12 · 2023: 9 · 2022: 24 · 2021: 15 · 2020: 16 · 2019: 17 · 2018: 14 · 2017: 19 · 2016: 17 · 2015: 15 · 2014: 19 · 2013: 17 · 2012: 12
- FWCI
- 1.70
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Briefings in Bioinformatics (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Cincinnati Children's Hospital Medical Center
- European Commission
- National Institutes of Health
- Topics
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biomedical Text Mining and Ontologies
- Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
- Keywords
- drug repurposing, rare diseases, orphan drug development, drug target identification, computational drug discovery
- MeSH terms
- Health Services Needs and Demand, Humans, Orphan Drug Production, United States, United States Food and Drug Administration, Rare Diseases, Drug Repositioning
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