A study conducted by the Institut de Neurociencies (INc-UAB) at UAB revealed the potential benefits of vorinostat in animal models following a stroke. Vorinostat, a drug commonly used to treat cutaneous T-cell lymphoma in humans, has been found to reduce brain damage and facilitate brain tissue restoration.
Ischemic stroke, the second leading cause of mortality globally, occurs when a blockage obstructs blood flow to the brain, resulting in brain damage and functional impairment due to oxygen depletion. Hypertension, a modifiable risk factor, is closely associated with worse stroke outcomes.
Currently, only one pharmacological treatment exists to alleviate stroke effects, but its efficacy varies among patients and is accompanied by significant adverse effects. The researchers at INc-UAB demonstrated that vorinostat (suberoylanilide hydroxamic acid) holds promise in treating stroke-induced brain lesions.
Vorinostat functions by inhibiting histone deacetylases, enzymes that regulate gene expression by modifying histone acetylation levels. In a study published in Biomedicine and Pharmacotherapy, the research group showed, in a hypertensive rat stroke model closely resembling the clinical scenario, that vorinostat administration during reperfusion improved neurological deficits, reduced brain damage, and attenuated inflammatory response, among other effects.
“We observed that a single dose of the drug, administered during the reperfusion phase, prevented various factors associated with stroke pathology. This sets the stage for further research involving this treatment beyond the preclinical stage,” explained Andrea Diaz, the article’s primary author.
Furthermore, the researchers demonstrated that vorinostat not only protects the brain but also the surrounding blood vessels, even several hours after the stroke onset.
“Considering the pressing clinical need for acute ischemic stroke drugs and vorinostat’s approval for human use, these findings should encourage further preclinical investigations to assess its effects in diverse scenarios such as female and elderly animals, animals with common stroke comorbidities like diabetes, and its long-term effects. This would lay the groundwork for well-designed clinical trials to evaluate its efficacy and safety in stroke patients,” concluded study coordinator Francesc Jimenez-Altayo, a researcher from UAB’s Department of Pharmacology, Therapeutics, and Toxicology and the Cardiovascular Diseases Area of the Centre for Biomedical Research Network (CIBERCV).