Year: 2022
Type: article
Abstract: Drug-resistant epilepsy remains a significant clinical and societal burden, with one third of people with epilepsy continuing to experience seizures despite the availability of around 30 anti-seizure drugs (ASDs). Further, ASDs often have substantial adverse effects, including impacts on learning and memory. Therefore, it is important to develop new ASDs, which may be more potent or better tolerated. Here, we report the preliminary preclinical evaluation of BICS01, a synthetic product based on a natural compound, as a potential ASD. To model seizure-like activity in vitro, we prepared hippocampal slices from adult male Sprague Dawley rats, and elicited epileptiform bursting using high extracellular potassium. BICS01 (200 μM) rapidly and reversibly reduced the frequency of epileptiform bursting but did not change broad measures of network excitability or affect short-term synaptic facilitation. BICS01 was well tolerated following systemic injection at up to 1,000 mg/kg. However, we did not observe any protective effect of systemic BICS01 injection against acute seizures evoked by pentylenetetrazol. These results indicate that BICS01 is able to acutely reduce epileptiform activity in hippocampal networks. Further preclinical development studies to enhance pharmacokinetics and accumulation in the brain, as well as studies to understand the mechanism of action, are now required.
Source: Frontiers in Neurology
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $2,950
Awards: G1311090270, G2189472788, G2628364946, G285994706, G3345895242, G4689608210, G4937468798, G5237714278, G5254896286, G593288916, Using human tissue to translate microRNA-based therapies for epilepsy, FutureNeuro, G6329715174, G6509606559, G7128578356, Using human tissue to translate microRNA-based therapies for epilepsy, G8156542052, G836282752, MicroRNAs in the Pathogenesis, Treatment and Prevention of Epilepsy, G8411905823, G8512683158
OpenAlex ID: W4206815627