Repurposing available drugs for neurodevelopmental disorders: The fragile X experience

Many available drugs have been repurposed as treatments for neurodevelopmental disorders. In the specific case of fragile X syndrome, many clinical trials of available drugs have been conducted with the goal of disease modification. In some cases, detailed understanding of basic disease mechanisms h...

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Bibliographic Details
Published in:Neuropharmacology 2019-03, Vol.147, p.74-86
Main Authors: Tranfaglia, Michael R., Thibodeaux, Clare, Mason, Daniel J., Brown, David, Roberts, Ian, Smith, Richard, Guilliams, Tim, Cogram, Patricia
Format: Article
Language:English
Subjects:
Animals
Disulfiram - pharmacology
Drug Repositioning
Fragile X Syndrome - drug therapy
Humans
Metoprolol - pharmacology
Minocycline - pharmacology
Motor Activity - drug effects
Randomized Controlled Trials as Topic
Sulindac - pharmacology
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Summary:Many available drugs have been repurposed as treatments for neurodevelopmental disorders. In the specific case of fragile X syndrome, many clinical trials of available drugs have been conducted with the goal of disease modification. In some cases, detailed understanding of basic disease mechanisms has guided the choice of drugs for clinical trials, and several notable successes in fragile X clinical trials have led to common use of drugs such as minocycline in routine medical practice. Newer technologies like Disease-Gene Expression Matching (DGEM) may allow for more rapid identification of promising repurposing candidates. A DGEM study predicted that sulindac could be therapeutic for fragile X, and subsequent preclinical validation studies have shown promising results. The use of combinations of available drugs and nutraceuticals has the potential to greatly expand the options for repurposing, and may even be a viable business strategy. This article is part of the Special Issue entitled ‘Drug Repurposing: old molecules, new ways to fast track drug discovery and development for CNS disorders’. •The history of drug repurposing efforts for fragile X is reviewed.•Results of an original repurposing study using transcriptomic data is presented.•Original results from preclinical validation of repurposing predictions are presented.•Sulindac is identified as a promising repurposing candidate for fragile X.•Metformin is confirmed as another promising candidate drug.
ISSN:0028-3908
1873-7064
DOI:10.1016/j.neuropharm.2018.05.004