The epileptic encephalopathies (EE), also known as epilepsy syndromes, are severe seizure disorders that start in childhood. The seizures are often frequent and drug-resistant, and they are associated with progressive impairment of the child’s cognition. There are a number of different epileptic encephalopathies, including West Syndrome, Dravet Syndrome, Lennox-Gastaut Syndrome, Doose Syndrome and Landau-Kleffner Syndrome (ESES). These are the syndromes currently being studied by EpLink.
The epileptic encephalopathies are rare – perhaps (1/1000-1/2000 live births) – but the cognitive impairment they cause is often permanent and lasts for life.
EpLink’s research objectives are: 1) to predict and prevent the onset of the new encephalopathies; 2) to provide early treatment for encephalopathies that can’t be prevented; 3) to provide better treatments for children with established encephalopathies; and 4) to develop a registry of patients with epileptic encephalopathies in order to promote future studies and clinical trials.
In Phase 3, drug development will be linked to genetic studies in order to produce new genetic models of the intractable epilepsies for the purposes of drug development, and preclinical studies in order to monitor seizure activity in these novel animal models.
Cannabis Extract in Refractory Epilepsy (CERES) Study
Anti-seizure drugs continue to be the first‐line treatment for epilepsy, and they successfully control seizures in about 2/3 of patients. Unfortunately, about 1/3 of patients have seizures that cannot be controlled with the drugs that are presently available. New drugs are needed for these patients. In particular, the use of cannabis extracts to treat seizures is a strong area of focus. Both cannabis and its cannabinoid-rich extracts are known to have anti-seizure actions. The two major cannabinoids present in the cannabis plant are cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC). Anecdotal reports suggest that both cannabinoids have anticonvulsant properties, and scientific reports support these observations. Although THC is psychoactive and would not be useful on its own for the therapy of epilepsy, CBD could be developed as an anti-seizure medication. Recent studies, including randomized controlled trials (RCTs), have confirmed that CBD is effective in reducing seizures in children and young adults with epilepsy at non-toxic doses. Thus, CBD represents a potential new therapy for use in the treatment of epilepsy.
The CERES study has been discontinued. EpLink is considering a future study on the effects of cannabinoids in adults with focal impaired awareness seizures (FIAS). This study would be a small open label, phase 2 trial designed to establish the effective doses that can be used in a future phase 3 (randomized, double blind, placebo controlled) trial. The study would compare: 1) CBD alone, and 2) CBD plus a small amount of THC. This research has been explored in animal models but further research is needed to examine effects in humans with FIAS.
Developmental Epileptic Encephalopathy (DEE) Registry
EpLink aims to establish a DEE Registry containing the clinical profiles of DEE patients with or without clinically diagnosed genetic abnormalities. The Registry will be created to help recruit patients with known genetic epileptic encephalopathies (EEs) for clinical trials, to examine the natural history of these patients, and develop personalized medicine approaches.
By establishing personalized treatment options for patients with DEE, we hope to offer better and/or more treatment options to this drug-resistant group of patients, where potential gene editing approaches may offer a cure.