Non-invasive Medical Device to Permeabilize the Blood-Brain Barrier Using Low Power Radio Frequency Evanescent Waves

The blood-brain barrier (BBB) is a highly selective semipermeable barrier that prevents bloodborne substances from non-selectively crossing into the brain. However, the BBB also significantly impedes the delivery of therapeutic agents into the brain. It has been reported that more than 95% of small molecule drugs and most large molecule drugs fail to cross the BBB. This presents a major challenge to the delivery of pharmacological agents for the treatment of various central nervous system (CNS) diseases, including Alzheimer’s and Parkinson’s Disease, and brain cancers such as glioblastoma and brain metastases. Several different approaches have been explored to make the BBB reversibly permeable, but to date, none have received FDA approval. In addition, nearly all the medical devices currently under development are large, expensive, and require surgery and/or treatment in a specialist clinic or hospital setting further adding to treatment costs. Some examples include focused ultrasound guided by MRI to agitate injected microbubbles, and pulsed ultrasound with a transducer array implanted in a skull window. Evanesc Therapeutics has developed an innovative medical device designated EvaPermea to reversibly permeabilize the BBB. Our non-invasive medical device uses low power radio frequency (RF) evanescent waves that are delivered to the patient’s head via flexible antennas. The antennas are integrated into a cap that the patient conveniently wears for only a few hours at home, with EvaPermea providing optimized RF dosage to permeabilize the BBB prior to drug treatment. The device can be used in a non-clinical setting and allows the patient to take the desired medications orally at home or via injectable routes. To the best of our knowledge, it is the only medical device of this type that could be used at home and is low-cost and accessible to patients. We hypothesize that the Evanesc’s device will provide a safe, effective, and convenient method for reversibly permeabilizing the BBB. Our preliminary data support this hypothesis, demonstrating a substantial increase in permeability of the BBB after treatment in vivo in a rat model. No adverse effects were observed. We will test this hypothesis in three Specific Aims in this SBIR Phase I: Aim 1. Determine the optimal power, duration and frequency of evanescent waves needed to effectively open the BBB. Aim 2. Determine kinetics of BBB closing after optimal evanescent wave treatment. Aim 3. Assess the safety of evanescent wave treatment. These studies will lead to the development of a low-cost, patient-friendly device for the safe and effective delivery of pharmacological agents to the CNS, which would have a major impact on the treatment of many CNS diseases. In our SBIR Phase II proposal, we aim to permeabilize the BBB and evaluate the efficacy of various chemotherapy drugs, including Paclitaxel and Doxorubicin, in treating glioblastoma through in vivo studies. The initial target market for EvaPermea is the treatment of glioblastoma and brain metastases, conditions that affect 200,000 people in the U.S. annually and have very low survival rates.