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.
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
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)
The American Academy of Neurology (AAN) and the American Epilepsy Society (AES) have provided new recommended practice guidelines for the management of new-onset and treatment-resistant epilepsy with anti-epileptic drugs (AEDs).1,2 The new guidelines highlight the evidence supporting the use of lamotrigine, vigabatrin, levetiracetam, pregabalin, gabapentin, and zonisamide for reducing the frequency of seizures in new-onset focal epilepsy and treatment-resistant epilepsy.
An expert subcommittee was formed consisting of members of the AAN and AES to update the 2004 evidence-based guidelines on epilepsy treatment with AEDs. Based on recent evidence, the investigators recommend the use of gabapentin and topiramate in adults and children with newly diagnosed epilepsy.
Class I and II studies support the use of rufinamide, ezogabine, clobazam, perampanel, and immediate-release pregabalin as add-on therapy in adults with treatment-resistant focal epilepsy; however, the adverse events associated with these therapies warrant careful consideration prior to prescribing. Other studies (class I, II, and III) suggest eslicarbazepine at 800 mg/day and 1200 mg/day may possibly be effective in treatment-resistant adult epilepsy.
For monotherapy recommendations in adults with new-onset epilepsy with either focal epilepsy or unclassified tonic-clonic seizures, lamotrigine should be considered over gabapentin or immediate-release carbamazepine due to better tolerability, according to class II evidence.
In addition, class II evidence appears to demonstrate no difference between controlled-release carbamazepine and levetiracetam or zonisamide in terms of reducing seizure frequency in patients with focal epilepsy or unclassified tonic-colonic seizures.
Lamotrigine is recommended over pregabalin in reducing secondarily generalized tonic-clonic seizures within a 6-month period. In adults with treatment-resistant focal epilepsy, class II evidence points to eslicarbazepine as a possibly effective monotherapy for reducing seizure frequency. Comparatively, levetiracetam, oxcarbazepine, and zonisamide may be an effective add-on therapy in pediatric patients with treatment-resistant focal epilepsy.
According to the guideline authors, there is a need for future studies which “use doses commonly used in clinical practice and use flexible-dosing regimens” in order to develop more definitive treatment recommendations.
Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs I: Treatment of new-onset epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society [published online June 13, 2018]. Neurology. doi:10.1212/WNL.0000000000005755
Kanner AM, Ashman E, Gloss D, et al. Practice guideline update summary: Efficacy and tolerability of the new antiepileptic drugs II: Treatment-resistant epilepsy: Report of the Guideline Development, Dissemination, and Implementation Subcommittee of the American Academy of Neurology and the American Epilepsy Society [published online June 13, 2018]. Neurology. doi:10.1212/WNL.0000000000005756
Source: Neurology Advisor By B. May
We have been posting about using Zebrafish to model epilepsy treatment since 2013, and about the potential for treatments to be developed from these models. Fast forward to 2017, and we have a viable treatment in clinical trials!
Via News Medical:
New drug discovered in zebrafish model of pediatric epilepsy shows promising results in clinical study
“Bench-to-bedside” describes research that has progressed from basic science in animal models that has led to therapies used in patients. Now, a study in the journal Brain describes what could be considered a direct “aquarium-to-bedside” approach, taking a drug discovered in a genetic zebrafish model of epilepsy and testing it, with promising results, in a small number of children with the disease. The study was supported by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
“This is the first time that scientists have taken a potential therapy discovered in a fish model directly into people in a clinical trial,” said Vicky Whittemore, Ph.D., program director at the NINDS. “These findings suggest that it may be possible to treat neurological disorders caused by genetic mutations through an efficient and precision medicine-style approach.”
Scott C. Baraban, Ph.D., the William K. Bowes Jr. Endowed Chair in Neuroscience Research and professor of neurological surgery at the University of California, San Francisco (UCSF), postdoctoral fellow Aliesha Griffin, Ph.D., and colleagues used a zebrafish model of Dravet syndrome to test the drug lorcaserin and found that it suppressed seizure activity in the fish. Dravet syndrome is a severe form of pediatric epilepsy characterized by frequent daily drug-resistant seizures and developmental delays. It is caused by a genetic mutation, which Dr. Baraban’s group was able to introduce into the zebrafish to cause epilepsy.
Via News Medical
Medtronic plc (NYSE: MDT) announced today that the first procedure using the Visualase(TM) MRI-Guided Laser Ablation System has been performed in the pivotal SLATE (Stereotactic Laser Ablation for Temporal Lobe Epilepsy) clinical trial at Mayo Clinic in Rochester, Minn. (more…)