This is a survey of the efficacy of perampanel as an add-on therapy in children with Dravet syndrome. Perampanel (a.k.a. Fycompa) was first approved in 2012, and last year its use was extended to pediatric patients. The authors were able to gather data on 10 Dravet patients - their average age was 11.5 years, [...]
When the human genome was sequenced in 2000, it was hoped it would simplify the search for medicines - just compare the genome of someone with a disease to the healthy standard, identify the mutated gene, and develop a drug targeting that gene product. It turned out disease states were much more complicated, usually [...]
This article brought forth some interesting observations. First, a major caveat - this study was done in mice. Mice with a relevant mutation in the Scn1a gene have proven to be a useful model of Dravet, but one must never directly extrapolate any results to humans. Dividing the day into three 8-hour periods, it [...]
Long-term safety and efficacy of cannabidiol in children and adults with treatment resistant Lennox-Gastaut syndrome or Dravet syndrome: Expanded access program results
A number of publications have appeared recently reporting on the efficacy and safety of cannabidiol (CBD) as an add-on therapy, as its clinical trials are concluding and its use is extending. This paper describes an "expanded access" program - that is, when the FDA allows access to a drug before approval. This is of [...]
(Ho et al. 2018) The Rare Epilepsy Network (REN), a collaboration among more than 30 rare epilepsy patient groups including the Dravet Syndrome Foundation, released the first summary of data collected through their web-based, patient-reported database. 795 patients and caregivers participated, 106 of which were identified as Dravet syndrome, representing the 3rd largest group of [...]
(Ruffolo et al. 2018) Gamma-aminobutyric acid (GABA) is a small compound that acts on different receptors in the brain such as GABAA and GABAB and is considered one of the main inhibitory neurotransmittors. Dysfunction of the GABAergic system is found in many neurological disorders, and although mutations in genes that code for subunits of GABA [...]
Evolution of Brain Glucose Metabolic Abnormalities in Children With Epilepsy and SCN1A Gene Variants.
(Kumar et al. 2018) Similar to the last study reviewed, the authors examined the fluorodeoxyglucose positron emission tomography (FDG-PET) scans of 3 patients with refractory epilepsy and SCN1A mutations. (Recall, FDG-PET scans provide images of the rate at which glucose is utilized by brain tissue.) However, in this study, the patients were imaged at least [...]
[18F]fluorodeoxyglucose-positron emission tomography study of genetically confirmed patients with Dravet syndrome.
(Haginoya et al. 2018) This study out of Japan examined the glucose uptake in the brain of 8 patients with Dravet syndrome, 4 of whom were three years or younger, and 4 of whom were 6 years and older. During the fluorodeoxyglucose positron emission tomography (FDG-PET) scan, the patients were injected with a chemically labeled [...]
(Richards et al. 2018) SCN1A is primarily expressed in inhibitory interneurons in the brain. These cells counteract the excitatory neurons, so mutations in SCN1A disrupt inhibition, leading to too much excitation and seizures. An ideal treatment would be one that encourages the inhibitory neurons to work more efficiently without simultaneously increasing excitatory neuron function. Based on previous [...]
(Frasier et al. 2018) It has long been known that SCN1A is expressed in heart cells as well as brain cells, and for several years scientists have hypothesized that the high rate of mortality in patients with Dravet syndrome could be due in part to some dysfunction in the heart caused by SCN1A mutations. The [...]