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


Newer epilepsy drugs fail to improve outcomes

Newer epilepsy drugs fail to improve outcomes

Overall treatment outcomes in patients with epilepsy have failed to improve, despite the proliferation of several newer antiepileptic drugs (AEDs) with different mechanisms, according to a recent study published in JAMA Neurology.

Treatment outcomes in patients with epilepsy have not improved, despite the advent of more than 15 newer antiepileptic drugs.


“Despite the availability of over 15 new drugs, overall seizure control in newly diagnosed patients has not fundamentally changed,” said senior author, Patrick Kwan, MD, PhD, Department of Medicine, The University of Melbourne, Parkville, Australia. “Newer AEDs are generally effective, and many have favorable safety profiles, but all have been reported to have efficacy similar to the established AEDs when used as monotherapy or adjunctive treatment.”

In a previous study, Dr. Kwan and colleagues initially followed 470 patients with newly diagnosed epilepsy between 1982 and 1998. They found that greater than one-third of patients continued to experience seizures despite AED treatment. Furthermore, subjects who exhibited no response to first or second AED regimens were likely to manifest refractory epilepsy.

In this current study, Dr. Kwan and colleagues sought to assess whether the overall treatment outcomes have changed with the advent of these additional drugs. They analyzed an expanded cohort of 1,795 newly diagnosed patients followed up from 1982 to 2014 at the Epilepsy Unit at the Western Infirmary.

The team followed 1,795 patients (53.7% male; median age: 33 years) in the current study for at least 2 years or until death. Median follow-up for the study was 11 years. They assessed the probability of attaining 1-year seizure freedom for each AED regimen, and used multivariable models to assess the associations between risk factors and AED treatment outcome after controlling for demographic and clinical characteristics.

The researchers defined an AED regimen as either monotherapy or a combination of two or more drugs. All initial regimens were montherapies.

During last follow-up, 1,440 patients (80.2%) received AED monotherapy and 355 patients (19.8%) took combinations of two or more AEDs.

In total, 1,144 patients (63.7%) were seizure free for 12 or more months, and 993 subjects (55.3%) became seizure free after treatment with a single AED. Further, 820 subjects (45.7%) attained at least 1 year of seizure freedom with their first AED monotherapy, and 208 subjects (28.0%) attained this freedom with a second regimen.

The team found that if an initial AED failed, second regimens led to seizure freedom 11.6% of the time and third regimens were effective in 4.4%.

“In our cohort, there had been a continual increase in the use of the new AEDs, both as initial and subsequent treatments, since the early 1990s,” the authors wrote. “Yet compared with our initial analysis in the first 470 patients, the seizure-free rate observed in the present study (63.7%) was virtually unchanged from that of 16 years ago (64.0%).”

Results of the present study also confirmed previous observations by the researchers that the chances of becoming seizure free drops with each subsequent AED regimen.

“Most patients who attain control do so with the first or second AED. The probability of achieving seizure freedom diminishes substantially with each subsequent AED regimen tried. More than one-third of patients experience epilepsy that remains uncontrolled,” the researchers concluded, adding that most newer AED drugs have similar mechanisms to old ones, and novel therapies are needed.

“We’re not being nihilistic and saying there’s no hope—for individual patients who tried a second and a third [regimen], there is a respectable chance [for seizure freedom]. But it does get harder after you try two or three drugs,” Dr. Kwan noted.

“Patients, their families, and doctors are desperate for new paradigms and novel approaches to treat epilepsy. We need new approaches, more adventurous approaches, rather than pouring more money into getting another ‘me-too’ drug out there,” he reflected.

Source: article by N. Saleh, MD, MS

Medication Adherence Key to Epilepsy Treatment

Medication Adherence Key to Epilepsy Treatment

In assessing the effectiveness of prescribed medication there is a strong emphasis on the ability of the patient to adhere to the regime recommended by the clinician. For individuals with epilepsy, adherence to medication is crucial in preventing or minimizing seizures and their cumulative impact on everyday life. Non-adherence to antiepileptic drugs (AEDs) can result in breakthrough seizures many months or years after a previous episode and can have serious repercussions on an individual’s perceived quality of life. Reasons for non-adherence are complex and multilayered. Patients can accidentally fail to adhere through forgetfulness, misunderstanding, or uncertainty about clinician’s recommendations, or intentionally due to their own expectations of treatment, side-effects, and lifestyle choice. (more…)

More Than a Third of Patients Do Not Respond to Antiepileptics

More Than a Third of Patients Do Not Respond to Antiepileptics

More than one-third of patients with newly diagnosed epilepsy do not respond to treatment with antiepileptic drugs (AEDs), according to a study published online Dec. 26 in JAMA Neurology.

Zhibin Chen, PhD, from the University of Melbourne in Australia, and colleagues conducted a longitudinal observational cohort study to assess long-term outcomes in 1,795 patients with newly diagnosed and treated epilepsy. Patients were followed for a minimum of two years or until death. (more…)

Nearly Half of Persons With Epilepsy Forget to Take Their Meds at Least Once a Month, Poll Shows

Nearly Half of Persons With Epilepsy Forget to Take Their Meds at Least Once a Month, Poll Shows

Almost half of epilepsy patients surveyed in a British poll say they’ve forgotten to take their medications at least once in the past month.

Researchers at Epilepsy Research UK wanted to know how meticulously people receiving their newsletter adhere to medication regimes. They stress, however, that these results pertain to a sample of 125 respondents and that the poll is still active.

Medication adherence is an important healthcare problem worldwide. According to a news release, across all fields of medicine, up to 75 percent of people don’t take their medicines properly. In epilepsy, forgetting to take anti-epileptic drugs could lead to seizures.

Respondents were asked to estimate for themselves how many times in the last month they had forgotten to take their medication at all – or had taken it a different time than recommended. This is what they answered:

  • 52 percent reported not forgetting to take their medicines – or give someone their medicines
  • Just over 20 percent said they had forgotten to take their medication once
  • About 25 percent reported forgetting to take their medication twice or more in the past month
  • 54 percent said they did not forget to take their medicine at the right time
  • 15 percent reported taking their medication at the wrong time once in the past month
  • Over 25 percent said they had taken their medicine at the wrong time at least twice in the past month.

In addition, the poll revealed that:

  • Almost 90 percent of the 125 respondents said they were responsible for their own epilepsy medication, while only 9 Percent said they were responsible for someones medication, as a caretaker or as a parent.
  • About 90 percent of respondents said they had to take medications two or more times per day, although most reported taking medication twice daily
  • About 50 percent of the respondents said they were taking just one medication, while 28 percent reported taking two different medications. Almost 25 percent of the poll’s respondents reported taking three, four or even more different medicines for their epilepsy daily.

Source: Epilepsy News Today