Cited by 358Pharmaceutical Economics and PolicyGenomics and Rare DiseasesStatistical Methods in Clinical Trials

The DOI matches its Crossref record; 163 of the 166 references it cites were found in a registry or an index.

Therapies for rare diseases: therapeutic modalities, progress and challenges ahead

Abstract

Most rare diseases still lack approved treatments despite major advances in research providing the tools to understand their molecular basis, as well as legislation providing regulatory and economic incentives to catalyse the development of specific therapies. Addressing this translational gap is a multifaceted challenge, for which a key aspect is the selection of the optimal therapeutic modality for translating advances in rare disease knowledge into potential medicines, known as orphan drugs. With this in mind, we discuss here the technological basis and rare disease applicability of the main therapeutic modalities, including small molecules, monoclonal antibodies, protein replacement therapies, oligonucleotides and gene and cell therapies, as well as drug repurposing. For each modality, we consider its strengths and limitations as a platform for rare disease therapy development and describe clinical progress so far in developing drugs based on it. We also discuss selected overarching topics in the development of therapies for rare diseases, such as approval statistics, engagement of patients in the process, regulatory pathways and digital tools.

Overview

Integrity signals

Registry

Crossref · 10.1038/s41573-019-0049-9

Cites

163 of 163 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Verification

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Citations

Cites

Show all 166 references

Research works printed but not linked: 5

  1. LiverTox: Clinical and Research Information on Drug-Induced Liver Injury [Internet]. Enzyme Replacement Therapy. National Institute of Diabetes and Digestive and Kidney Diseases https://www.ncbi.nlm.nih.gov/books/NBK548796/ (2016).
  2. Field, M. J. & Boat, T. F. (eds) Rare Diseases and Orphan Products (National Academies Press, 2010).
  3. Journal of Gene Medicine. Gene therapy clinical trials worldwide. Wiley http://www.abedia.com/wiley/vectors.php (2018).
  4. Kaiser, J. New gene-editing treatment might help treat a rare disorder, hints first human test. Science https://doi.org/10.1126/science.aav3226 (2018). · DOI
  5. Alliance for Regenerative Medicine. Quarterly data report Q3. ARM http://alliancerm.org/wp-content/uploads/2018/10/ARM_Q3_2018_Web-1.pdf (2018).

Cited by

Sorted by citations

Items 101–200 of 358

Metadata

Authors
Tambuyzer, E., Vandendriessche, B., Austin, C. P., Brooks, P. J., Larsson, K., Miller Needleman, K. I., Valentine, J., Davies, K., Groft, S. C., Preti, R., Oprea, T. I., & Prunotto, M.
Affiliations
  • Rare Disease Foundation (CA)
  • Case Western Reserve University (US)
  • National Institutes of Health (US)
  • European Medicines Agency (NL)
  • University of Oxford (GB)
  • University of New Mexico (US)
  • University of Geneva (CH)
Corresponding author
  • Tambuyzer, Erik
  • Prunotto, Marco
Venue
Nature Reviews Drug Discovery
Published
2019-12-13
Volume
19
Issue
2
Pages
93-111
ISSN
  • 1474-1776 (ISSN-L)
  • 1474-1784
OpenAlex
W2994844251
Cited by
357
References
166
Citations by year
2026: 44 · 2025: 52 · 2024: 70 · 2023: 68 · 2022: 58 · 2021: 43 · 2020: 21 · 2019: 1
FWCI
8.52
Type
journal article
Language
en
Open access
closed
Locations
  • Nature Reviews Drug Discovery (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Social Sciences › Economics, Econometrics and Finance › Economics and Econometrics › Pharmaceutical Economics and Policy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
  • Physical Sciences › Mathematics › Statistics and Probability › Statistical Methods in Clinical Trials
Keywords
rare diseases, orphan drugs, therapeutic modalities, small molecules, monoclonal antibodies, protein replacement therapy, oligonucleotides, gene therapy, cell therapy, drug repurposing, drug development, regulatory pathways, patient engagement, digital tools, translational gap
MeSH terms
Drug Development, Humans, Orphan Drug Production, Drug Approval, Rare Diseases, Drug Repositioning

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.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review