Drug discovery and development for rare genetic disorders
Open accessAbstract
Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated.
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Many rare diseases still lack effective cures and call for new therapeutics.
“Despite the great efforts that have been devoted to supporting the development of orphan drugs, many rare diseases still lack effective cures and call for new therapeutics.[3]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [3]
Recent progress in gene therapies could offer more options for treating GARDs.
“Since a majority of GARDs stem from genetic disorders, recent progresses in gene therapies could offer more options for treating GARDs.[3, 5]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [3]
A majority of GARDs stem from genetic disorders.
“Since a majority of GARDs stem from genetic disorders, recent progresses in gene therapies could offer more options for treating GARDs.[3, 5]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [3]
An increasing number of RNA molecules are emerging as promising breakthrough therapies for many diseases.
“Recently, an increasing number of RNA molecules are emerging as promising breakthrough therapies for many diseases.[3]”
From RNA delivery biomaterials for the treatment of genetic and rare diseases (2019) · cites this paper as [3]
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Polypharmacology by Design: A Medicinal Chemist’s Perspective on Multitargeting Compounds
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- Authors
- Sun, W., Zheng, W., & Simeonov, A.
- Affiliations
- National Institutes of Health (US)
- Corresponding author
- Simeonov, Anton
- Venue
- American Journal of Medical Genetics Part A
- Publisher
- Wiley
- Published
- 2017-07-21
- Volume
- 173
- Issue
- 9
- Pages
- 2307-2322
- ISSN
- 1552-4825 (ISSN-L)
- 1552-4833
- PMC
- PMC5662129
- OpenAlex
- W2738402542
- Cited by
- 107
- References
- 109
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 22 · 2023: 8 · 2022: 10 · 2021: 11 · 2020: 19 · 2019: 5 · 2018: 8 · 2017: 3
- FWCI
- 1.23
- Type
- journal article
- Language
- en
- Open access
- green
- europepmc.org
- Locations
- American Journal of Medical Genetics Part A (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Center for Advancing Translational Sciences (Z99 TR999999)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Physical Sciences › Computer Science › Computational Theory and Mathematics › Computational Drug Discovery Methods
- Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
- Keywords
- rare diseases, drug discovery, drug development, pharmacogenetics, whole genome sequencing, high-throughput screening, target-based screening, phenotypic screening, drug repurposing, gene therapy, recombinant protein, autologous transplantation, disease models, induced pluripotent stem cells, animal models, biomarkers, clinical trials
- MeSH terms
- Animals, Disease Models, Animal, Humans, United States, Genetic Therapy, Genetic Diseases, Inborn, Rare Diseases, Small Molecule Libraries, Drug Discovery, Induced Pluripotent Stem Cells
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
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