Drug Therapy

The most common seizures in adults are complex partial seizures, which often start at the sides of the brain – regions known as the temporal lobes. These seizures are very hard to control with standard anti-seizure drugs.

Preclinical evidence from animal models show that cannabidiol (CBD) – the extract in medical marijuana that doesn’t make you high – has anticonvulsant effects. Dr. McIntyre Burnham’s lab at the University of Toronto found that a combination of CBD and tetrahydrocannabinol (THC) works better to reduce the number of seizures than CBD or THC alone in rat models of complex partial seizures.

In addition, along with an industry partner, EpLink has organized a clinical study examining the effects of CBD in adults with drug-resistant epilepsy. The study will begin in Phase 3 and assess whether CBD plus a low dose of THC will decrease the number of motor seizures in adults with refractory (drug-resistant) epilepsy. This study will also examine the genetic profile of participants in an effort to understand the genes associated with epilepsy and whether different epilepsy syndromes respond to treatment with medical cannabis. If the results are positive, it is hoped that CBD will gain wider acceptance as a new therapy for seizure control.

During Phase 2, EpLink identified other new targets for drug development. Dr. Burnham’s group found that a progesterone-like compound (called dihydroprogesterone) combined with a solvent (benzyl alcohol) suppressed seizures in the same rat model of complex partial seizures.

At the Krembil Research Institute, Dr. James Eubanks and collaborators examined the activity of a new type of anti-seizure drug in animal studies of Rett Syndrome, a genetic disorder that may result in both intellectual disability and seizures. “Rett-like” mice have an overly active protein called histone deacetylase 6 (HDAC6). Dr. Eubanks’ group found that the drugs worked by inhibiting HDAC6 activity, thereby stopping seizures in animal epilepsy models (i.e. in wild-type mice). Researchers are working with EpLink’s industrial partners to test the toxicity of the drugs for chronic use. If the drugs are well tolerated, then the group can begin submitting applications to move the drugs towards clinical use.