A new, smart implant that “listens” to brain signals could help treat epilepsy and other neurological conditions, such as Parkinson’s disease.
Could an innovative brain-stimulating device make a difference to the treatment of neurological conditions?
Doctors use neurostimulation to treat various conditions, including epilepsy, the effects of stroke, and even depression. This treatment involves using special devices that send electrical impulses to control the activity of the brain and central nervous system.
Doctors sometimes also use this technique to improve the symptoms of Parkinson’s disease, a neurological condition that affects physical balance and the ability to move or coordinate the movement of the limbs.
However, the neurostimulator devices that are currently available for the treatment of neurological conditions are unable to both stimulate brain activity and record it at the same time.
Now, specialists from the University of California (UC), Berkeley have developed a new, sophisticated neurostimulator that seems able to achieve this. It may have the potential to improve the treatment of epilepsy, Parkinson’s, and other conditions.
The research team has named this device “WAND,” which stands for “wireless artifact-free neuromodulation device.” WAND has two tiny external controllers, each of which monitors 64 electrodes that sit in the brain.
This device can monitor electrical activity in the brain and learn to identify abnormal signals that indicate the presence of a seizure or tremors. WAND can then help modulate electrical signals in the brain to prevent such events and symptoms.
Unlike similar existing devices, which can only record electrical activity from up to eight points in the brain, WAND can track activity from 128 different channels.
New device is cost- and time-efficient
In their study paper, which the journal Nature Biomedical Engineering has published, the researchers note that, in the future, WAND could potentially help improve the lives of people who have seizures or live with various neurological conditions.
“The process of finding the right therapy for a patient is extremely costly and can take years,” explains assistant professor Rikky Muller, one of the researchers.
“Significant reduction in both cost and duration can potentially lead to greatly improved outcomes and accessibility. We want to enable the device to figure out what is the best way to stimulate for a given patient to give the best outcomes. And you can only do that by listening and recording the neural signatures.”
Muller and team have tested WAND in an animal model, using rhesus macaques to show how the device can learn to recognize brain signals for specific arm movements and how it can then act on those same signals.
After a while, the implanted devices learned to detect the neural signals that corresponded to the macaques’ hand motions. Once they had identified these patterns, they were able to send out electrical signals that delayed the hand movements.
“While delaying reaction time is something that has been demonstrated before, this is, to our knowledge, the first time that it has been demonstrated in a closed-loop system based on a neurological recording only,” says Muller.
“In the future, we aim to incorporate learning into our closed-loop platform to build intelligent devices that can figure out how to best treat you and remove the doctor from having to constantly intervene in this process,” she adds.
WAND double-activity may boost treatment
The researchers explain that the currently available neurostimulator devices are unable to detect signature electrical signals in the brain while also modulating such signals.
This, they note, is because the electrical pulses that the neurostimulator emits “obscure” the original brain signals, thus rendering them virtually undetectable.
“In order to deliver closed-loop stimulation-based therapies, which is a big goal for people treating Parkinson’s and epilepsy and a variety of neurological disorders, it is very important to both perform neural recordings and stimulation simultaneously, which currently no single commercial device does,” says study co-author Samantha Santacruz, previously a researcher at UC Berkeley and now an assistant professor at the University of Texas in Austin.
Unlike other neurostimulators, WAND devices have a unique design with custom integrated circuits that are able to record the subtle electrical signals that the brain emits while also sending out stronger impulses to “correct” faulty signals.
Thanks to WAND, “[b]ecause we can actually stimulate and record in the same brain region, we know exactly what is happening when we are providing a therapy,” notes Muller.
Source: Medical News Today by M. Cohut
For people with severe epilepsy, no medication is effective – but a radical approach of implanting stem cells into the brain could stop seizures at their source.
The technique, which has so far shown promise in rats, would involve taking some of a patient’s own skin cells and turning them into embryonic-like stem cells in the lab. These can then be directed to become a kind of brain cell that damps down seizures.
Epilepsy arises when there is an imbalance between two different kinds of nerve cell in the brain; excitatory ones, which cause other cells to fire, and inhibitory ones, which block firing. Seizures result when excitation swamps inhibition.
For some people with epilepsy, the surge of excitation starts in one part of the brain, called the hippocampus, before spreading elsewhere. So Ashok Shetty at Texas A&M University and his colleagues tried boosting inhibition at that site to see what would happen.
First, Shetty’s team injected 38 rats with a chemical that triggers a long seizure. The resulting brain damage causes the animals to have spontaneous seizures, starting from the hippocampus, over the next few months.
A week after the initial damage, the team implanted inhibitory brain cells in the hippocampi of about half the rats. Five months later, those given implanted cells had 70 per cent fewer seizures than those without implants.
To check it was really the inhibitory cells working, five implanted animals were given cells that were genetically modified to stop firing when the animal was dosed with a drug. When under the drug’s influence, these mice had about the same number of seizures as mice that hadn’t had any cells implanted.
Dissections also showed that the implanted cells survived in the hippocampus.
Shetty says the treatment could be suitable for people whose seizures originate in a small part of their hippocampus, and whose only other option is surgery to remove that part. They could try a cell implant instead, and if something went wrong, they could have all the graft removed along with the epileptic brain tissue. And if the therapeutic cells were made from a patient’s own skin, they wouldn’t need medicines to stop rejection.
The study isn’t proof this approach will work, though, says Bruno Frenguelli at the University of Warwick, UK. The rats were given implants soon after their brain damage, and it isn’t clear if the technique would help people with seizures stemming from a head injury in the past, which is a common cause of epilepsy.
Journal reference: PNAS, DOI: 10.1073/pnas.1814185115
SOURCE: Written By C. Wilson for NewScientist.com
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)