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 neuroenetherapeutics.com.

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 musc.edu. For more information on hospital patient services, visit muschealth.org.

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 frd.musc.edu.

Source: MEDICAL UNIVERSITY OF SOUTH CAROLINA

Electronic device used to detect, treat epileptic seizures in mice

Electronic device used to detect, treat epileptic seizures in mice

Researchers are hoping an electronic device used to detect, stop and prevent epileptic seizures in mice can be used to treat other neurological disorders, according to a study published in Science Advances.

In the study led by a U.K. research team, scientists looked at the benefits of “direct in situ electrophoretic drug delivery to treat neurological disorders.” The team developed a neural probe with a microfluidic ion pump for on-demand drug delivery and electrodes for recording neural activity.

“The (device) works by electrophoretically pumping ions across an ion exchange membrane and thereby delivers only the drug of interest and not the solvent,” wrote lead author Christopher M. Proctor, of the University of Cambridge, and colleagues. “This ‘dry’ delivery enables precise drug release into the brain region with negligible local pressure increase.”

The device’s therapeutic potential was then implanted and tested on anesthetized mice in which seizure-like events (SLEs) were induced. According to the study, the probe was able to detect the pathological activity and stop seizures by delivering the drug directly to the source. Based on the results, researchers are hoping further development of the device could be used to treat other neurological disorders.

“The (microfluidic ion pump) probe demonstrated the capability to detect, stop, and even completely prevent SLEs in an animal model by timely delivery of inhibitory neurotransmitters to the seizure source,” the authors concluded. “Although this work is focused on epilepsy treatment, we anticipate that tailored engineering of the (microfluidic ion pump) platform will enable additional applications for electrophoretic drug delivery in neural interfacing and the treatment of neurological disorders.”

Source: Clinical-Innovation.com

FUTURE – Brain implant could stop epilepsy seizures

FUTURE – Brain implant could stop epilepsy seizures

For many people who suffer from neurological disorders, such as epilepsy, there are no viable treatment options. In our latest research, we developed an implantable device that may one day offer relief. We show that the implant can treat problems in the brain, such as epileptic seizures, by delivering brain chemicals – known as neurotransmitters – directly to the cells in the brain that cause the problem.

The implant works by using an electric field to push neurotransmitters out of the device from an internal reservoir. This process, known as electrophoresis, allows for precise control over the dose and timing of drug delivery, which is important for addressing intermittent disorders such as epilepsy. (more…)

Moving Toward Enhanced Regenerative Medicine To Cure Epilepsy

At the border between regenerative medicine and neural engineering lies enhanced regenerative medicine. Using brain tissue modulated by electronic components, EU research has tackled the most common form of epilepsy.

Photo© Gabriella Panuccio

Temporal lobe epilepsy (TLE) is the most common form of epilepsy and yet, the most unresponsive to treatment. Patients have a typical pattern of progressive brain damage that affects cognitive and emotional processes. (more…)

Flexible drug delivery microdevice to advance precision medicine

Flexible drug delivery microdevice to advance precision medicine

A Korea Advanced Institute of Science and Technology (KAIST research team has developed a flexible drug delivery device with controlled release for personalized medicine, a step toward theragnosis.

Theragnosis, an emerging medical technology, is gaining attention as key factor to advance precision medicine with simultaneous diagnosis and therapeutics.

Photo: The flexible drug delivery device for controlled release fabricated via inorganic laser lift off. Credit: KAIST

Theragnosis devices including smart contact lenses and microneedle patches integrating physiological data sensors and drug delivery devices. The controlled drug delivery has fewer side effects, uniform therapeutic results, and minimal dosages compared to oral ingestion. Recently, some research groups conducted in-human applications of bulky, controlled-release microchips for osteoporosis treatment. However, they failed to demonstrate successful human-friendly flexible drug delivery systems for controlled release.

For this microdevice, the team under Professor Daesoo Kim from the Department of Biological Science and Professor Keon Jae Lee from the Department of Materials Science and Engineering, fabricated a device on a rigid substrate and transferred a 50 μm-thick active drug delivery layer to the flexible substrate via inorganic laser lift off. The device shows mechanical flexibility with the capability of precise administration of exact dosages at desired times. The core technology is a freestanding gold capping layer directly on top of the micro-reservoir containing the drugs, previously regarded as impossible in conventional microfabrication.

The flexible drug delivery device for controlled release attached on a glass rod. Credit: KAIST

This flexible drug delivery system can be applied to smart contact lenses or the brain disease drug delivery implants. In addition, when powered wirelessly, it will represent a novel platform for personalized medicine.

In animal experiments, the team treated epilepsy by releasing anti-epileptic medication through the device. Professor Lee believes the flexible microdevice will further expand the applications of smart contact lenses, therapeutic treatments for brain disease, and subcutaneous implantations for daily healthcare.

This study “Flexible Wireless Powered Drug Delivery System for Targeted Administration on Cerebral Cortex” was published in the June issue of Nano Energy.

Source and Photo Credits –  Provided by: The Korea Advanced Institute of Science and Technology (KAIST)

 

RECENT NEWS