A study led by researchers at RCSI (Royal College of Surgeons in Ireland) has identified a new genetic test that can be used to predict if a patient with epilepsy will develop an adverse reaction to a common anti-epileptic drug. The finding will help inform doctors to prescribe the safest and most beneficial treatment for patients with epilepsy.

The study, “Genetic variation in CFH predicts phenytoin-induced maculopapular exanthema in European-descent patients,” is published in the journal Neurology.

The research has identified a genetic factor that can be used to predict whether a patient with epilepsy will develop a rash in reaction to a common anti-epileptic drug called phenytoin. Phenytoin is used worldwide and is the most commonly prescribed anti-epileptic drug in developing countries.

Dr. Mark McCormack of the Department of Molecular and Cellular Therapeutics, RCSI, and first author on the paper commented: ‘Our finding will make it easier for clinicians to predict a troublesome rash which occurs as an allergic reaction to the drug phenytoin. Adverse reactions can sometimes cause more harm to patients than seizures and patients may stop taking otherwise useful drugs as a result of the side-effects. Through genetic testing we can now estimate a patient’s risk prior to placing them on phenytoin.’

Professor Gianpiero Cavalleri, Associate Professor in Human Genetics at RCSI and the FutureNeuro SFI Research Centre, coordinated the study. ‘This work represents a step towards more holistic, personalized care of epilepsy by improving patient safety and targeting the right drug to the right patient,’ Professor Cavalleri said.

Smart Monitor, a Silicon Valley, CA-based provider of clinically validated solutions for the management of complex chronic conditions has announced the launch of SmartWatch Inspyre for the Apple Watch.  The new Apple Watch app uses a unique algorithm to recognize a wearer’s repetitive shaking movements, similar to those caused by convulsive seizures.

Designated family members and care providers are alerted upon onset of these movement patterns so they can intervene in a timely manner to maximize safety of their loved one. The episodic data is captured in a secure HIPAA-compliant cloud for review and analysis.

SmartWatch Inspyre users can also summon help with the push of a button. Alerts can be sent to any phone, anywhere, and detailed reports of each event can be securely accessed for later review with physicians.

“We are pleased to be able to offer Inspyre on the Apple Watch,” said Anoo Nathan, CEO in a statement. “This really is a game changer for patients and families alike. Inspyre enhances the safety and autonomy of people prone to seizures while providing peace of mind for families and loved ones.

The purpose of the Brivaracetam Clinical Trial is to evaluate the pharmacokinetics (PK), safety, and tolerability of brivaracetam (BRV) administered intravenously (iv) in subjects between 1 month and 16 years of age with epilepsy.

Eligibility Criteria

Inclusion Criteria:

• Male or female from >= 1 month to < 16 years of age. For subjects who are < 1 year from birth and who were preterm infants, the corrected gestational age should be used for this entry requirement
• Weight >= 3 kg (6.6 lbs)
• Diagnosis of epilepsy
• Acceptable candidate for venipuncture and intravenous (iv) infusion
• Treatment with >=1 anti epileptic drug (AED; including BRV) without a change of dose regimen for at least 7 days prior to Screening
• No treatment with vagus nerve stimulation (VNS), OR the subject is being treated with VNS and the settings have been constant for >=7 days prior to Screening
• For female subjects: not of childbearing potential, OR of childbearing potential and not sexually active/negative pregnancy test, OR of childbearing potential and sexually active/negative pregnancy test/uses medically acceptable contraceptive methods

Exclusion Criteria:

• Subject has previously received iv Brivaracetam (BRV) in this study
• Subject is being treated with BRV at a dose >5mg/kg/day (rounded) or >200mg/day for subjects with body weights >40kg
• Subject requires or is likely to require a change in concomitant antiepileptic drug(s) (AED[s]), dose of concomitant AED(s), or formulation of AED(s) during the 7 days prior to the intravenous (iv) pharmacokinetic (PK) Period
• Subject is likely, in the opinion of the Investigator, to require rescue medication during the Initiating Oral BRV (IOB) Treatment or iv PK Periods
• Subject has experienced generalized convulsive status epilepticus in the 28 days prior to Screening or during the Screening Period

Delayed first-line benzodiazepine treatment is independently associated with major adverse outcomes in children with status epilepticus (SE), according to a JAMA Neurology study. The results raise the question as to whether poor outcomes could, in part, be prevented by earlier administration of treatment.

Patients in the status epilepticus study were admitted with refractory convulsive SE to 11 pediatric tertiary hospitals in the United States and stratified into two groups — those who received timely first-line benzodiazepine (i.e., given within less than 10 minutes of seizure onset); and those who received treatment within 10 or more minutes.

The status epilepticus study associated an untimely treatment with a higher frequency of death, use of continuous infusions, longer convulsion duration, and more frequent hypotension. These findings may change the perception of acute seizure and status epilepticus treatment, tentatively converting it into an extremely time-sensitive emergency that is similar to stroke or other cardiovascular events.

Dr. Nagai’s research found that training patients to increase their levels of alertness helped them to become better at calming their brain and reducing seizures.

Forty patients with drug-resistant temporal lobe epilepsy, aged 18 to 70, were recruited for a controlled trial from three screening centres. Some 45 percent of patients demonstrated a reduction in seizures of 50 percent or more. Dr. Nagai said: “Our clinical study provides evidence for autonomic biofeedback therapy as an effective and potent behavioural intervention for patients with drug-resistant epilepsy… This approach is non-pharmacological, non-invasive and seemingly side-effect free.”

The U.S. Food and Drug Administration has accepted for review a New Drug Application for clobazam Oral Soluble Film (clobazam OSF) for adjunctive treatment of seizures associated with Lennox-Gastaut syndrome in patients two years of age or older. The target date for completion of the FDA review is the third-quarter of 2018.

Clobazam OSF is administered using Aquestive’s PharmFilm drug delivery technology. Similar in size and thickness to a stamp, Aquestive’s PharmFilm dissolves instantly after being placed on the tongue and can be administered without water.

Two multicenter controlled studies were conducted to evaluate the bioequivalence of clobazam OSF with clobazam tablets, a benzodiazepine currently on market, at the same dosage strengths. Based on the studies, clobazam OSF was demonstrated to be bioequivalent to clobazam tablets and have comparable safety.

A database focused on repurposing drugs to treat epilepsy has been released by the University of Liverpool. The aim of the project is to help prioritize the most promising candidates for drug repurposing.

Repurposing drugs offers the potential of significant savings in the time and cost of drug development by discovering new indications for approved drugs. Given that 20 to 30 percent of individuals with epilepsy do not respond to traditional medications, there is a need to identify new antiepileptic drugs.

The database is reliable: 94 percent of the included drugs have corroborative evidence of efficacy in animal models. The database includes many drugs that are appealing candidates for repurposing, as they are widely accepted by prescribers and patients.

We previously found that genetic mutants with reduced expression or activity of Scn8a are resistant to induced seizures and that co-segregation of a mutant Scn8a allele can increase survival and seizure resistance of Scn1a mutant mice. In contrast, Scn8a expression is increased in the hippocampus following status epilepticus and amygdala kindling. These findings point to Scn8a as a promising therapeutic target for epilepsy and raise the possibility that aberrant overexpression of Scn8a in limbic structures may contribute to some epilepsies, including temporal lobe epilepsy.

Using a small-hairpin-interfering RNA directed against the Scn8a gene, we selectively reduced Scn8a expression in the hippocampus of the intrahippocampal kainic acid (KA) mouse model of mesial temporal lobe epilepsy. We found that Scn8a knockdown prevented the development of spontaneous seizures in 9/10 mice, ameliorated KA-induced hyperactivity, and reduced reactive gliosis.

These results support the potential of selectively targeting Scn8a for the treatment of refractory epilepsy.