From the January 2015 issue of HealthCare Business News magazine
Many classes of drugs are being developed for the treatment of serious brain disorders including malignant brain tumors, Parkinson's disease and Alzheimer's disease. Despite great promise demonstrated in preclinical studies, these agents' success in clinical trials has been limited in part by the BBB compromising their ability to reach the diseased tissue.
Clinically significant benefits often require direct injection of the compounds into the brain, which is risky and not practical for many patients, and therefore difficult to justify in the early stage of disease progression when the drugs are potentially the most effective. Researchers in academia and industry are developing drug carriers or new routes of administration, but moving drugs across the BBB remains a challenge.
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Focused ultrasound can reversibly increase the permeability of the blood brain barrier, thereby temporarily allowing drugs to pass through and into the surrounding brain tissue. The mechanical effects of focused ultrasound - often enhanced and controlled by the use of microbubbles - can loosen the dense network of endothelial cells joined by tight junctions, enhancing the release of drugs from the bloodstream into the brain tissue.
The first clinical trial to investigate the ability of focused ultrasound to non-invasively open the BBB is set to begin soon in Canada, for treatment of patients with malignant brain tumors.
Activating and mapping the brain
Clinical interest is also growing for using focused ultrasound to reversibly alter neural activity in the brain for a range of potential indications. There are many diagnostic and therapeutic clinical applications that rely on precise stimulation or suppression of neural activity. Commonly used techniques include deep brain stimulation (DBS), electrical monitoring, electroporation or electromagnetic stimulation. Functional imaging modalities such as fMRI are also used to map brain activity. The U.S. Brain Research through Advancing Innovative Neurotechnologies (BRAIN) Initiative is spurring interest and innovation in neuromodulation, via large investments (hundreds of millions) in new tools to map the circuits of the brain and/or alter their function.
These current techniques may be effective for some patients yet not for others. DBS and electrical monitoring may require invasive procedures, whereas the non-invasive options may be less precise. Focused ultrasound could offer a non-invasive and precise alternative for stimulation or suppression of neural activity, depending on the parameters of the ultrasound energy applied to the tissue. Neuromodulation can be achieved through either pulsing of the ultrasound using specific sequences to induce small mechanical perturbation of the nerve cells, or by subtly raising the temperature of the tissue.
