Aduhelm, the newly approved drug for Alzheimer's disease, can remove some of the amyloid that forms the brain plaques that are characteristic of the disease. But most of the medication is wasted because it impacts the blood-brain barrier, which protects the brain from toxins and infections but also keeps out many medications.
Therefore, the researchers attempted to open the blood-brain barrier for a short time while administering the drug, a monoclonal antibody, using highly precisely targeted ultrasound pulses along with small gas bubbles to open the barrier.
Researchers at West Virginia University reported their results in The New England Journal of Medicine. When the barrier was opened, 32 percent more plaque dissolved, said Ali Rezai, the neurosurgeon who led the study. The group did not measure the amount of antibodies entering — which would require radiolabeling the drug — but in animal studies, opening the barrier allowed five to eight times more antibodies to enter the brain, Rezai said.
The experiment, tested in three patients with mild Alzheimer's, was a preliminary safety study and was not designed to measure clinical outcomes. Other researchers said it was an innovative but difficult approach to one of the most challenging problems in treating brain diseases.
Alzheimer's drugs like aducanumab, which Biogen sells as Aduhelm, are expensive; Aduhelm's list price is $28,000 a year. Walter Koroshetz, director of the National Institute of Neurological Disorders and Stroke, said one of The reasons for the price is that only 1 percent of antibodies injected into the bloodstream cross the blood-brain barrier.
The barrier is located at the ends of several important blood vessels. Upon entering the head, the vessels branch and divide until, at their tips, they form narrow capillaries with extremely narrow walls. This keeps large molecules out and allows small molecules, such as glucose and oxygen, in.
In the study, patients were first injected with microbubbles of perfluorocarbon gas. Low-frequency ultrasound pulses were then focused on the area of the brain to be treated. The pulses generated waves in the fluid in the blood vessels; The microbubbles expanded and contracted rapidly with the waves. This opened the glasses without damaging them.
But the procedure was designed to apply ultrasound to a small area. In Alzheimer's cases, the plaque is found throughout the brain. A larger study will be needed to determine if the treatment improves outcomes.
Several similar studies involving patients with a variety of brain ailments are in early stages, and so far all show that the method works. One group, led by Nir Lipsman, a neurosurgeon at the University of Toronto's Sunnybrook Research Institute, opened the door to delivering a chemotherapy drug to the brains of four breast cancer patients whose cancer had spread to the brain. The concentration of the drug, trastuzumab, quadrupled, the group said.
Kullervo Hynynen, vice president of the Sunnybrook Research Institute, is hopeful. “If this works safely, it will open the doors to an entirely new way of treating the brain.“, he claimed.
GINA KOLATA. THE NEW YORK TIMES
BBC-NEWS-SRC: http://www.nytsyn.com/subscribed/stories/7080743, IMPORTING DATE: 2024-01-22 18:52:03
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