Repurposing Vorinostat for the Treatment of Disorders Affecting Brain

AbstractBased 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 neurorestor ative 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, especial ly 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...
Source: NeuroMolecular Medicine - Category: Neurology Source Type: research