Neuroene Therapeutics awarded $1.5 million to develop anti-seizure compound for epilepsy

Neuroene Therapeutics awarded $1.5 million to develop anti-seizure compound for epilepsy

With funding from NIH Phase II SBIR grant, Neuroene Therapeutics will take the next steps toward bringing their vitamin K analogues for drug-resistant epilepsy to clinical trial

Neuroene Therapeutics, a start-up company founded by mitochondrial biologist Sherine S. L. Chan, Ph.D. and medicinal chemist C. James Chou, Ph.D. of the Medical University of South Carolina, has received a $1.5 million NIH Phase II Small Business Innovation Research grant to optimize vitamin K analogues that could improve seizure control in patients with drug-resistant epilepsy. Richard Himes, Ph.D., a chemist at the College of Charleston, serves as the company’s Chief Scientific Officer.

Photo: Dr. Chan and Dr. Chou are the founders of Neuroene Therapeutics, an MUSC start-up company that was awarded a 1.5M SBIR Phase II grant to develop a novel anti-seizure compound for drug-resistant epilepsy.

Of the 3.4 million Americans estimated to have epilepsy, one third do not receive adequate seizure control with current medications, either because the drugs do not work for them or because they cannot tolerate the drug’s side effects.

The SBIR grant will enable Neuroene Therapeutics to test the efficacy and safety of its lead compounds, which are analogues of a naturally occurring form of vitamin K that is essential for mitochondrial and neuronal health.

“Mitochondria are the powerhouses of the cell, and the brain needs a lot of energy for its function. A particular form of vitamin K protects the integrity of the mitochondria and helps them produce enough energy for brain cells,” explained Chan.

The form of vitamin K needed by the brain is not the same as the vitamin K we get from foods in our diet. The vitamin K we eat must first be processed by intestinal bacteria before transport to the brain, and then within neurons must be converted into the specific form of Vitamin K that is needed for mitochondrial and neuronal health.

Because the compound developed by Neuroene Therapeutics mimics this specific form of Vitamin K that the neuron needs (not the ingested form) and because it travels directly to the brain, it bypasses the need for transport systems.

“Unlike other vitamin K analogues, which require additional processing before they are in a usable form, our compounds are a direct substitute for the active form and go directly to the brain where they are needed,” said Chou.

Early testing of these vitamin K analogues by the MUSC investigators with pilot funding from the South Carolina Clinical and Translational Research Institute, a Clinical and Translational Science Awards hub funded by the National Institutes of Health, showed significantly reduced seizure activity with little toxicity in a zebrafish model. Testing in mouse seizure models at the National Institute of Neurological Disorders and Stroke Anticonvulsant Screening Program confirmed those findings.

With assistance from the MUSC Foundation for Research Development, Chan and Chou established Neuroene Therapeutics in 2015 and received a patent on their lead compounds earlier this year.

The current SBIR award will enable additional testing of the compounds’ efficacy and safety at the University of Utah’s Anticonvulsant Drug Development Program, directed by Karen Wilcox, Ph.D., which has robust rodent models of drug-resistant epilepsy. By the end of the two years of SBIR funding, Neuroene Therapeutics will have identified the lead compound to take forward into clinical trial.

Although Neuroene Therapeutics is focused currently on developing its lead compound for drug-resistant epilepsy, Chan and Chou are also studying whether vitamin K analogues could improve outcomes in other difficult-to-treat neurological diseases. They already have some promising preclinical data in Parkinson’s disease and mitochondrial DNA depletion syndrome. In addition, they speculate that the compounds could also be relevant to Alzheimer’s disease.

Apolipoprotein E4, one of the strongest genetic risk markers for late-onset Alzheimer’s disease, has a role to play in vitamin K transport. It is possible, then, that mitochondrial dysfunction due to insufficient transport of vitamin K could be implicated in Alzheimer’s and, if so, these brain-penetrating vitamin K analogues could bypass the transport process, thus improving mitochondrial health and disease outcome.


About Neuroene Therapeutics

Neuroene Therapeutics is a startup biotechnology company developing novel Vitamin K-based therapeutics for neurological disorders such as epilepsy. The company originated from collaborative research between Medical University of South Carolina investigators C. James Chou, Ph.D., and Sherine Chan, Ph.D., who cofounded and continue to lead Neuroene Therapeutics. Visit us at

About MUSC

Founded in 1824 in Charleston, The Medical University of South Carolina is the oldest medical school in the South. Today, MUSC continues the tradition of excellence in education, research, and patient care. MUSC educates and trains more than 3,000 students and residents, and has nearly 13,000 employees, including approximately 1,500 faculty members. As the largest non-federal employer in Charleston, the university and its affiliates have collective annual budgets in excess of $2.2 billion. MUSC operates a 700-bed medical center, which includes a nationally recognized Children’s Hospital, the Ashley River Tower (cardiovascular, digestive disease, and surgical oncology), Hollings Cancer Center (a National Cancer Institute-designated center) Level I Trauma Center, and Institute of Psychiatry. For more information on academic programs or clinical services, visit For more information on hospital patient services, visit

About the South Carolina Clinical and Translational Research Institute

The South Carolina Clinical and Translational Research (SCTR) Institute is the catalyst for changing the culture of biomedical research, facilitating sharing of resources and expertise, and streamlining research-related processes to bring about large-scale, change in the clinical and translational research efforts in South Carolina. Our vision is to improve health outcomes and quality of life for the population through discoveries translated into evidence-based practice.

About MUSC Foundation for Research Development

FRD has served as MUSC’s technology transfer office since 1998. During that period, FRD has filed patent applications on more than 400 technologies, resulting in over 150 U.S issued patents. Additionally, FRD has executed more than 150 licenses and spun out more than 50 startup companies. MUSC startups have had products approved by the FDA and acquired by publicly traded corporations while attracting substantial investment dollars into South Carolina. Innovations from MUSC, including medical devices, therapies and software, are positively impacting health care worldwide. Please visit us online at


FDA Expands Use of Epilepsy Drug Perampanel (Fycompa) to Younger Children

FDA Expands Use of Epilepsy Drug Perampanel (Fycompa) to Younger Children

The US Food and Drug Administration (FDA) has granted expanded approval of perampanel (Fycompa, Esai Inc) for the treatment of “partial-onset seizures (POS) with or without secondary generalized seizures” in patients as young as 4 years, the manufacturer reports.

The expanded indication is for both monotherapy and adjunctive use in patients 4 years of age and older.

The drug was initially approved in 2012 as adjunctive treatment for POS. This was followed in 2015 by approval as adjunctive treatment for primary generalized tonic-clonic seizures in patients with epilepsy who were at least 12 years of age, and in 2017 as monotherapy for POS with or without secondary generalized seizures in the same age group.

To date, the drug “is approved in 55 countries and has treated more than 200,000 patients worldwide across all indications,” the company reported in a press release.

The new approval for the antiepileptic drug (AED) includes both film-coated tablet and oral suspension formulations. The former is available in 2-, 4-, 6-, 8-, 10-, and 12-mg doses; the latter is available at a dose of 0.5 mg/mL.

“Taking an AED as prescribed every day is a critical part of reaching the goal of seizure freedom for pediatric patients,” Jesus Eric Piña-Garza, MD, pediatric neurologist at TriStar Medical Group Children’s Specialists, Nashville, Tennessee, said in the same release.

“With Fycompa, children and their parents now have a once-daily dosing option with a long half-life that can fit into their increasingly busy lives,” added Piña-Garza.

AMPA Receptor Antagonist

It is currently estimated that approximately 470,000 US children have epilepsy. Of these, up to 40% will have uncontrolled seizures even with existing treatments.

“Fycompa has a long half-life and in a pharmacokinetic study, it has been demonstrated that in the event of a missed dose, plasma levels remain relatively stable,” it adds.

The drug is a selective, noncompetitive alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor antagonist.

In addition to past phase 3 trials of adults with POS, two safety studies of children with epilepsy aged 4 to 11 years have been conducted. In the safety studies, 225 pediatric patients received the drug at baseline, 110 were exposed to the drug for at least 6 months, and 21 were exposed for at least a year. Adverse reactions “were similar to those seen in patients 12 years of age and older,” the company reports. It adds that final results of these studies will be presented at an upcoming medical meeting.

The company notes that perampanel, “like other AEDs, may cause suicidal thoughts or actions in a very small number of people, about 1 in 500.” It also may cause psychiatric problems, such as new or worse aggressive behavior or hostility, hallucinations, paranoia, confusion, extreme changes in mood, or memory difficulties.

Other adverse events (AEs) may include dizziness, sleepiness, increased risk for falls, and serious allergic reactions. The most commonly reported AEs include dizziness, tiredness, irritability, falls, nausea and vomiting, and weight gain.

The US Drug Enforcement Administration has designated the product as a federally controlled substance (CIII).


FDA Approves Stiripentol for Dravet Syndrome Seizures

FDA Approves Stiripentol for Dravet Syndrome Seizures

The US Food and Drug Administration today approved stiripentol (Diacomit) for the treatment of seizures associated with Dravet syndrome epilepsy. This is just the second approved form of treatment specifically for patients with Dravet syndrome.

The drug is approved for use in patients 2 years of age and older who are taking clobazam. Stiripentol is not supported by clinical data for use as a monotherapy option for Dravet syndrome.

Stiripentol is available in capsules to be taken orally, or in powder form for oral suspension. The daily dosage is 50mg/kg/day taken in 2 or 3 divided doses (16.67 mg/kg three times daily or 25 mg/kg twice daily). Capsules should be swallowed whole with water during a meal. The powder form should be mixed in water and taken immediately after a meal.

Data from two 12-week studies of stiripentol are included in the FDA’s prescribing information for Diacomit. The studies included 33 patients receiving Diacomit and 31 receiving placebo for a period of 8 weeks. All patients were 3 to ≥18 years of age and taking both clobazam and valproate.

The primary efficacy endpoint of both studies was the responder rate, with responders defined as patients who experienced a greater than 50% decrease in the frequency (per 30 days) of generalized clonic or tonic-clonic seizures during the double-blind treatment period compared to the 4-week baseline period.

In Study 1, the responder rate for patients taking stiripentol was 71% (15 of 21) compared to 5% taking placebo (1 of 20). For Study 2, the response rates were 67% (8 of 12) and 9.1% (1 of 11), respectively.

The most commonly reported side effects of stiripentol, occurring in ≥10% of patients and more frequently than on placebo, included somnolence (67%), decreased appetite (45%), agitation (27%), ataxia (27%), weight decreased (27%), hypotonia (24%), nausea (15%), tremor (15%), dysarthria (12%), and insomnia (12%).

Earlier this year, the FDA approved the use of cannabidiol (Epidiolex) oral solution for the treatment of seizures associated with Dravet syndrome as well as Lennox-Gastaut syndrome, another rare and severe form of epilepsy.

Source: Article by Cecilia Pessoa Gingerich for

Early Treatment Failure More Likely With Carbamazepine vs Lamotrigine in Epilepsy

In patients with epilepsy, moderate-quality evidence indicates that treatment failure for any reason related to therapy or adverse events (AEs) occurs significantly earlier with carbamazepine than with lamotrigine, although the results for time to first seizure imply that carbamazepine may be superior to lamotrigine for seizure control. Results of the review were published in the Cochrane Database of Systematic Reviews.

The current analysis was an individual participant data review. The primary outcome was time to treatment failure, and secondary outcomes included time to first seizure postrandomization; time to 6-month, 12-month, and 24-month remission; and incidence of AEs.

Among the 14 trials included in this review, individual participant data were available for 2572 of 3787 eligible patients from 9 of 14 trials — 68% of the potential data. In terms of remission outcomes, a hazard ratio (HR) of <1 indicated an advantage for carbamazepine. For first seizure and treatment failure outcomes, an HR of <1 indicated an advantage for lamotrigine.

Lamotrigine showed an advantage over carbamazepine in time to treatment failure for any reason related to treatment (pooled HR adjusted for seizure type: 0.71; 95% CI, 0.62-0.82; moderate-quality evidence) and time to treatment failure because of AEs (pooled HR adjusted for seizure type: 0.55; 95% CI, 0.45-0.66; moderate-quality evidence); however, there was no difference between the 2 therapies for time to treatment failure because of lack of efficacy (pooled HR for all participants: 1.03; 95% CI, 0.75-1.41; moderate-quality evidence).

However, time to first seizure (pooled HR adjusted for seizure type: 1.26; 95% CI, 1.12-1.41; high-quality evidence) and time to 6-month remission (pooled HR adjusted for seizure type: 0.86; 95% CI, 0.76-0.97; high-quality evidence) demonstrated a significant advantage for carbamazepine over lamotrigine for first seizure and 6-month remission.

No difference was observed between the 2 agents for time to 12-month remission (pooled HR for all participants: 0.91; 95% CI, 0.77-1.07; high-quality evidence) or time to 24-month remission (HR for all participants: 1.00; 95% CI, 0.80-1.25; high-quality evidence). Because only 2 trials followed participants for >1 year, however, evidence was limited.

The results of this review are applicable primarily to persons with focal onset seizures, with 88% of included participants experiencing this type of seizure at baseline. Moreover, seizures in up to 50% of persons who were classified as experiencing generalized onset seizures at baseline may have been misclassified. Rates of AEs were similar between the 2 agents.

The investigators concluded that although the methodologic quality of the included trials was generally good, some evidence suggests that the design choice of masked or open-label treatment may have influenced the treatment failure or withdrawal rates reported in these studies. They recommend that future trials be designed to the highest quality possible, taking into account masking, selection of patient population, classification of seizure type, choice of outcomes and analysis, duration of follow-up, and presentation of results.


Nevitt SJ, Tudur Smith C, Weston J, Marson AG. Lamotrigine versus carbamazepine monotherapy for epilepsy: an individual participant data review. Cochrane Database Syst Rev. 2018;6:CD001031.


French regulator says up to 4,100 children victims of epilepsy drug

French regulator says up to 4,100 children victims of epilepsy drug

25e49-Depakine-Chrono-300mg-100compPARIS (Reuters) – An estimated 2,150 to 4,100 children in France suffered a major malformation in the womb between 1967 and 2016 after their mothers took a treatment against epilepsy and bipolar disorders known as valproate, France’s drug regulator said on Thursday.

Valproate, which has been manufactured in France by Sanofi under the brand Depakine in the field of epilepsy and Depakote and Depamide in bipolar disorders, is also believed to cause slow neurological development. (more…)