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01-12-2021 | Spinal Muscular Atrophy | Review

Repurposing Vorinostat for the Treatment of Disorders Affecting Brain

Authors: K. V. Athira, Prashant Sadanandan, Sumana Chakravarty

Published in: NeuroMolecular Medicine | Issue 4/2021

Abstract

Based on the findings in recent years, we summarize the therapeutic potential of vorinostat (VOR), the first approved histone deacetylase (HDAC) inhibitor, in disorders of brain, and strategies to improve drug efficacy and reduce side effects. Scientific evidences provide a strong case for the therapeutic utility of VOR in various disorders affecting brain, including stroke, Alzheimer’s disease, frontotemporal dementia, Parkinson's disease, Huntington's disease, amyotrophic lateral sclerosis, spinal muscular atrophy, X‐linked adrenoleukodystrophy, epilepsy, Niemann-Pick type C disease, and neuropsychiatric disorders. Further elucidation of the neuroprotective and neurorestorative properties of VOR using proper clinical study designs could provide momentum towards its clinical application. To improve the therapeutic prospect, concerns on systemic toxicity and off-target actions need to be addressed along with the improvement in formulation and delivery aspects, especially with respect to solubility, permeability, and pharmacokinetic properties. Newer approaches in this regard include poly(ethylene glycol)-b-poly(dl-lactic acid) micelles, VOR-pluronic F127 micelles, encapsulation of iron complexes of VOR into PEGylated liposomes, human serum albumin bound VOR nanomedicine, magnetically guided layer-by-layer assembled nanocarriers, as well as convection-enhanced delivery. Even though targeting specific class or isoform of HDAC is projected as advantageous over pan-HDAC inhibitor like VOR, in terms of adverse effects and efficacy, till clinical validation, the idea is debated. As the VOR treatment-related adverse changes are mostly found reversible, further optimization of the therapeutic strategies with respect to dose, dosage regimen, and formulations of VOR could propel its clinical prospects.

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Title: Repurposing Vorinostat for the Treatment of Disorders Affecting Brain
Authors: K. V. Athira
Prashant Sadanandan
Sumana Chakravarty
Publication date: 01-12-2021
Publisher: Springer US
Keyword: Spinal Muscular Atrophy
Published in: NeuroMolecular Medicine / Issue 4/2021
Print ISSN: 1535-1084
Electronic ISSN: 1559-1174
DOI: https://doi.org/10.1007/s12017-021-08660-4

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Repurposing Vorinostat for the Treatment of Disorders Affecting Brain

Abstract

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

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