Developing A Hybrid Neuroprosthesis For Epilepsy Treatment: A Status Report

By Nandor Ludvig, M.D.

As announced in our 2004 Summer newsletter, the NYU Comprehensive Epilepsy Center had initiated an ambitious program to develop a novel intracranial therapeutic device for the treatment of epilepsies that are both drug-resistant and unsuited for surgery. The device, US Patent No. 6,497,699, is named as “Hybrid Neuroprosthesis,” or HNP. The name implies that the invention is a hybrid of electrophysiological and pharmacological components. It serves to correct abnormal neural functions, and, like other prostheses, it is fully implanted in the body.

The basic idea behind the development of the HNP is that since many forms of epileptic seizures originate in well defined epileptogenic zones in the brain, the optimal way to treat these seizures is to get access to the very sites of these epileptogenic zones and treat them locally. This strategy makes surgical tissue removal unnecessary, yet allows the exposure of the epileptogenic zones to appropriately high concentrations of antiepileptic drugs without inducing side-effects. The HNP aims to translate this strategy into a medical implant, which records EEG activity in the epileptogenic zones, recognizes abnormal EEG signals prior to an imminent clinical seizure, and prevents the development of this seizure by delivering antiepileptic drugs into the epileptogenic zones.

Since the announcement of this research program last year, our research team has made significant progress in the preclinical work that should precede the actual clinical trials. First, we refined the animal model that serves to test the function of the HNP before the clinical trials. Some key data was published in 2004, in the journal Epilepsia (vol. 45; Suppl.7; pages 212-213). This animal model, employing monkeys, is necessary as neither computer models nor tissue cultures are able to simulate the complex interactions between an epileptogenic zone and an implanted HNP.

Second, to extract as much information as possible from these demanding animal experiments, we collected new data for demonstrating that localized antiepileptic drug deliveries in the primate brain do produce antiepileptic effects, and that the intracranial catheters for such drug deliveries cause no apparent behavioral abnormalities or harmful tissue damage.

Third, we modified our original HNP software, named “SeizureGuard,” to recognize abnormal, epileptiform EEG signals specifically in the mentioned monkey model of epilepsy. This will allow us to test in this model the ability of the HNP to deliver antiepileptic drugs in response to the signs of an imminent seizure. In fact, we have made progress in developing a second version of this software which can recognize abnormal epileptiform EEG signals in epileptic patients prior to clinical seizures. This software development effort uses electrophysiological data collected with our EEG systems at Tisch Hospital. A unique feature of the SeizureGuard software is that it uses relatively simple calculations and, as a consequence, it can run on processors that do not consume much electricity. For fully implanted devices, such as the HNP, this will be an important advantage.

Fourth, our collaboration with Lenox Laser (Glen Arm, Maryland) led to a $132,000 grant from the National Institutes of Health (NIH). While the primary aim of this project is to develop a method for delivering and sampling proteins in brain, it has also helped us to improve the drug delivery catheter of the HNP. This improved catheter will allow the delivery of antiepileptic drugs via laser-made, microscopic perforations, filtering out the surrounding brain cells and thus eliminating the possibility of catheter-clogging.

Fifth, a milestone was reached by completing the development of the first prototype of the minipump that will mediate the drug deliveries into the epileptogenic zones. This cylindrical minipump, weighing less than 15 grams and having a diameter of as small as 15mm, can be periodically refilled through the skin. Importantly, the design of this minipump also allows its continuous control by the SeizureGuard software. As a consequence, the minipump will be able to deliver drugs into the brain only when necessary: for the duration of abnormal, epileptiform EEG signals.

The main task that is now ahead of us is to integrate all the existing components into a single, flawlessly operating, implantable device, equipped with a power supply module that is harmlessly rechargeable through the skin, and completed with a periodically active radiotelemetry system so the physician can occasionally check the status of the implant. For this work, we applied for a $ 2.7 million grant to the National Institutes of Health (NIH). This fund will also be vital for establishing a laboratory for intracranial therapeutic device development at NYU.

The main participants of this project from the Epilepsy Center are: Nandor Ludvig, M.D., Ph.D, who is the Principal Investigator, and Co-Investigators Orrin Devinsky, M.D., Ruben I. Kuzniecky, M.D. and Werner K. Doyle, M.D. The bioengineers involved in the studies are: Lorant Kovacs, M.S., from ESCO (software development), Geza Medveczky, M.S., from G-tech (minipump development), and Frank Bihari from Apollo Microsurgicals and Walter Blumenfeld, M.S., from Lenox Laser (HNP electrode and catheter development). We also receive consultation from EEG expert Solomon L. Moshe, M.D. (Albert Einstein College of Medicine), neuropathologist Marc Del Bigio, M.D., Ph.D (University of Manitoba) and anesthesiologist Jean Charchafl ieh, M.D. (SUNY Downstate Medical Center). The progress we have made so far hopefully conveys to the reader that each and every member of this team gives his utmost effort to one day make the vision of the HNP a clinical reality.