A Vitamin K analogue could be utilised as a potential treatment for the medication-resistant seizures caused by mitochondrial dysfunction, reveals a new study published in the Journal of Medicinal Chemistry.
The drug which forms a new class of anti-seizure medication was developed by the researchers at the Department of Drug Discovery and Biomedical Sciences in MUSC’s College of Pharmacy and Neuroene Therapeutics.
The orally deliverable compound which is a modified form of the naturally occurring vitamin K, was found to effectively eliminate seizure activity in the mouse models, noted the study.
“The drug showed remarkable brain penetration, and was rapidly distributed in the central nervous system and is well-tolerated in mice and rats,” explained one of the authors Dr Sherine S. L. Chan.
“We are targeting a new mechanism of action — mitochondrial dysfunction — that is a big underlying cause for neurological disease,” he added.
Mitochondria functions as a storehouse of energy for the cells. Mitochondrial dysfunction in the brain cells would affect their function requiring a significant amount of energy which is an underlying cause to many neurological diseases, including epilepsy, Parkinson’s disease and rare mitochondrial disorders.
Currently, available treatments for medication-resistant epilepsy mostly include invasive procedures such as implanting a responsive neurostimulation device in the brain, vagus nerve stimulation (through an implant in the brain) and epilepsy surgery.
The uniqueness of the structure of the new Vitamin K3 analogue is responsible for the increased functionality of the drug say the researchers. The compound which is named as 3d attenuated seizures in a dose-dependent manner in the mouse 6 Hz and maximal electric shock (MES) models.
“Treatment with the compound increased the brain cells’ ability to produce energy,” showed the researchers. The compound 3d also remained non-toxic up to a dose of 800 mg/kg and protected the mitochondrial health,” noted the authors.