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Erschienen in: NeuroMolecular Medicine 4/2021

04.05.2021 | Review

Repurposing Vorinostat for the Treatment of Disorders Affecting Brain

verfasst von: K. V. Athira, Prashant Sadanandan, Sumana Chakravarty

Erschienen in: NeuroMolecular Medicine | Ausgabe 4/2021

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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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Metadaten
Titel
Repurposing Vorinostat for the Treatment of Disorders Affecting Brain
verfasst von
K. V. Athira
Prashant Sadanandan
Sumana Chakravarty
Publikationsdatum
04.05.2021
Verlag
Springer US
Erschienen in
NeuroMolecular Medicine / Ausgabe 4/2021
Print ISSN: 1535-1084
Elektronische ISSN: 1559-1174
DOI
https://doi.org/10.1007/s12017-021-08660-4

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