August 2014 issue
August 31, 2014 | While many forms of neuromodulation apply electrical stimulation directly to a target area to achieve a neurological effect, a novel approach uses neurostimulation to produce an indirect effect, specifically, opening the blood-brain barrier in order to augment pharmacological therapies. Recently, two different teams reported research and commercial progress in developing this therapeutic strategy.
A team of researchers from the Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences reported in the journal Technology their new Vascular Enabled Integrated Nanosecond pulse (VEIN pulse) procedure, which consists of inserting minimally invasive needle electrodes into diseased brain tissue and applying multiple bursts of nanosecond pulses with alternating polarity. The researchers believe that the bursts disrupt tight junction proteins responsible for maintaining the integrity of the BBB without causing damage to the surrounding tissue. This technique is being developed for the treatment of brain cancer and neurological disorders, such as Parkinson’s disease.
The BBB is a network of tight junctions that normally acts to protect the brain from foreign substances by preventing them from leaking out of blood vessels. However, it also limits the effectiveness of drugs to treat brain disease. Temporarily opening the BBB is a way to ensure that drugs can still be effective.
For the treatment of brain cancer, “VEIN pulses could be applied at the same time as biopsy or through the same track as the biopsy probe in order to mitigate damage to the healthy tissue by limiting the number of needle insertions,” said Rafael Davalos, director of the bioelectromechanical systems laboratory at Virginia Tech.
Additionally, the group showed that VEIN pulses can be applied without causing muscle contractions, which may dislodge the electrodes and require the use of a neuroblocker and general anesthesia. According to Christopher Arena, co-lead author on the paper with Paulo Garcia and Michael Sano, “The fact that the pulses alternate in polarity helps to avoid unwanted, electrically induced movement. Therefore, it could be possible to perform this procedure without using a neuroblocker and with patients under conscious sedation. This is similar to how deep brain stimulation is implemented clinically to treat Parkinson’s disease.”
The team now plans to translate the technology into clinical applications through a university spin-out company, VoltMed, Inc.
Meanwhile, BrainsGate, the Israeli manufacturer of stroke neuromodulation devices, announced that the data safety monitoring board for the company’s ImpACT24 study examined the effect and safety results in an interim analysis and determined that the measured effect justifies the continuation of the study. There were no safety concerns, and in order to maximize the possibility of success in the study, the board felt that increasing the sample size from 450 to 800-1000 patients is appropriate.
BrainsGate’s Ischemic Stroke System is based on an implantable electrode designed to deliver electrical stimulation to the spheno-palatine ganglion. Upon activation (using an external system temporarily attached to the patient’s cheek), the system augments cerebral blood flow. Treatment can be either acute or chronic. In addition, the stimulation regimen selected determines the biological effect: a mild stimulation profile leads to gentle augmentation of cerebral perfusion aiding in the management of ischemic stroke or dementia, while a different, more intense regimen enhances the bioavailability of drugs in the CNS by increasing the permeability of the BBB.
