Precision medicine for rare diseases: The times they are A-Changin'. (April 2022)

• Record Type: Journal Article
• Authors: Amaral, Margarida D.
• Is Part Of: Current opinion in pharmacology. Volume 63(2022)
• Publication Date: 2022-04
• Subjects: CF cystic fibrosis -- CFTR CF transmembrane conductance regulator -- EMA European Medicines Agency -- ER endoplasmic reticulum -- ERQC ER quality control -- FDA Food and Drug Administration -- NMD nonsense-mediated decay -- ODD orphan drug designation -- PM plasma membrane -- PTC premature termination codon -- RD rare disease -- SME small and medium-sized enterprise; Pharmacology -- Periodicals; Pharmaceutical Preparations -- Periodicals; Drug Therapy -- Periodicals; Biopharmaceutics -- Periodicals; Pharmacologie -- Périodiques; Pharmacology; Periodicals; 615.105
• DOI: 10.1016/j.coph.2022.102201
• Languages: English
• ISSNs: 1471-4892

Abstract

Abstract: The greatest challenge of current biomedicine is to identify curative therapies for every disease in a personalized way so that every individual gets benefit. To that end, however, we need fully understand mechanisms of disease that will drive the design of novel therapies and innovative approaches. For rare diseases (RDs) which individually affect low numbers of people (< 1:2000), but together, affect 300 million (∼10% of the world population) the constraints are greater. This is because: 1) there is limited knowledge on RD physiopathology; 2) the low number of patients strongly limits clinical trials; 3) there is low commercial interest by pharma; 4) when specific drugs reach the market, their high cost precludes their reaching all those who need them. Several possibilities that can help mitigate these barriers are discussed here, including orphan drug designation, drug repurposing, break-down into theratypes (as currently in place for Cystic Fibrosis), or novel precision-medicine-based approaches. Highlights: Finding curative therapies for rare diseases (RDs) is a major unmet need. High RD heterogeneity, low patient number, and weak pharma interest are key hurdles. Orphan drug designation and drug repurposing open promising paths. Breaking down sub-types of RDs into theratypes can help finding "common" drugs. Precision medicine can overcome drug development barriers for RDs.