How Focused Ultrasound Could Help Curb Parkinson's

There are two major obstacles to developing effective drugs for Alzheimer's, Parkinson's, and other diseases that destroy the brain. The first is overcoming the blood-brain barrier, and the second is delivering the drug to a specific area and making sure that it does not spread to the rest of the brain.

Now, a new approach that uses ultrasound beams and microbubbles could be a noninvasive way to deliver drugs safely to particular locations in the brain.

The method is called focused ultrasound (FUS) and promises to open the door to thousands of drugs that could treat a variety of brain conditions if they could cross the blood-brain barrier.
Scientists at Columbia University who developed the FUS device have now shown that it facilitated in curbing early Parkinson's disease progression and improve brain function in mice.

The FUS technique briefly opens the blood-brain barrier in a specific part of the brain to allow drugs to reach just that area. The blood-brain barrier is an intricate feature of the blood vessels that feed the brain and the rest of the central nervous system. The barrier prevents pathogens and possibly harmful substances crossing over from the bloodstream into the parenchyma, or functional tissue, of the brain.

The FUS technique beams ultrasound pulses through the skull to a precise location in the brain. When the pulses meet microbubbles that researchers have injected into the bloodstream, they cause the microbubbles to oscillate between the walls of the blood vessels.

The oscillating microbubbles cause a reversible increase in the permeability of the blood-brain barrier in that location. When the FUS beams stop, the microbubbles stop oscillating, and the brief access through the blood-brain barrier closes.

For the study, the team focused on Parkinson's disease. They showed that they could use FUS to distribute brain-altering genes and proteins across the blood-brain barrier. Once across the barrier, the genes and proteins partly restored dopamine-releasing pathways in the brain. Loss of ability to make dopamine — a chemical messenger that is important for controlling movement — is an early sign of Parkinson's disease.

The researchers also noted reductions in some of the behavioral symptoms of Parkinson's disease in the mice.

"We found both behavioral and anatomical neuronal improvements in the brain," says Elisa Konofagou, one of the senior study authors who is a professor of biomedical engineering and radiology.

Prof. Konofagou says that she and her team are the first to use available drugs to restore a dopamine-releasing pathway in early Parkinson's disease.

The Food and Drug Administration (FDA) recently granted the researchers an Investigational Device Exemption so that they can safely test it as a way to deliver drugs in humans with Alzheimer's disease.

The results were posted in a recent Journal of Controlled Release study paper.

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