Blood-Brain Barrier Opening

The blood-brain barrier (BBB) is a protective layer of tightly joined cells that lines the blood vessels in the brain and prevents harmful substances, such as toxins and infectious agents, from diffusing into the surrounding brain tissue.

Unfortunately, it also limits the amount of medication that can reach diseased brain targets. Safely and temporarily opening this barrier to deliver therapeutics to the brain is a long-sought goal for treating a wide range of neurologic conditions, including brain tumors, Alzheimer’s disease and epilepsy.

Focused ultrasound has been shown to disrupt the BBB in a noninvasive, safe, and targeted manner. It is capable of reliably producing a therapeutic window of up to four hours immediately after treatment. The mechanical effects of focused ultrasound, namely cavitation, are thought to be the principle cause behind this BBB disruption. Small bubbles used as a contrast agent during ultrasound imaging procedures are injected into the bloodstream during the focused ultrasound procedure. These bubbles, called microbubbles, oscillate in the vessels and put pressure on the endothelium and force apart the tight junctions.

This method of BBB disruption – focused ultrasound with microbubbles – has had very promising results. Normally only small molecules (typically smaller than 400 Da) with the proper charge and hydrophilicity can cross the BBB, but disruption of this barrier with FUS has been shown to enable molecules as large as 150 kDa to cross.

Temporary opening of the blood-brain barrier in a safe and targeted manner with focused ultrasound unlocks a vast array of potential treatments. Immunotherapies such as IL-12 or even entire immune cells, as well as chemotherapeutics, can be delivered to notoriously difficult to treat brain tumors with this technique. Various therapeutic drugs and molecules, including gene therapies, can be delivered for the treatment of depression, Parkinson’s disease, and Huntington’s disease among many other neurological disorders. This technique is being tested clinically for the treatment of various brain tumors, ALS, and Alzheimer’s disease.

Webinars:

Focused Ultrasound for the Temporary Opening of the Blood-Brain Barrier by Elisa Konofagou, PhD, Columbia University

Click here for additional references from PubMed.