A small study shows that sound waves make Alzheimer’s medication cross the brain barrier

A small study shows that sound waves make Alzheimer’s medication cross the brain barrier

In the first study of its kind in humans, researchers have discovered that it is safe to use sound waves fired at specific areas of the brain to open a protective barrier and pave the way for Alzheimer’s medications. The study, published in the New England Journal of Medicine, included only three patients, but raises hope about the long-term potential of the treatment strategy known as focused ultrasound.

“We want to be very careful. This is the first three people in the world to have received this (treatment). I think what we’ve learned from this can help us,” said Ali Rezaei, lead author of the study and CEO and director of the Rockefeller Neuroscience Institute at West Virginia University.

Rezaei stressed that the goal of the research is not to replace pharmaceutical treatments, but rather to improve their benefits by helping more of the drug penetrate the brain.

Nature has provided humans with a barrier made of tightly packed cells that prevents harmful toxins, such as viruses, bacteria and fungi, from reaching the brain. This armor, known as the blood-brain barrier, has posed a major challenge for decades to scientists trying to treat neurodegenerative diseases such as Alzheimer’s and Parkinson’s, which affect at least 7 million Americans. The barrier is a closed door that prevents about 98 percent of treatments from reaching the brain.

By using focused ultrasound, “what we want to do is nudge individuals toward the milder stages of Alzheimer’s disease with fewer plaques to give them a fighting chance,” Rezaei explained.

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Two men and a woman with mild loss of memory, learning, concentration, and decision-making skills due to Alzheimer’s disease participated in the study. The patients, who ranged in age from 59 to 77, were given six monthly doses of the federally approved — if somewhat controversial — laboratory-based antibody aducanumab, which is sold under the brand name Adohelm. The antibody, which is injected directly into the patient’s vein, reduces a sticky substance in the brain called amyloid beta, which clumps between nerve cells and disrupts their function.

About two hours after giving the drug to patients, the researchers used focused ultrasound to open the protective barrier in one hemisphere of the patient’s brain, but not in the other. The hemisphere that received focused ultrasound plus the antibody saw harmful beta-amyloid plaques reduced by an average of 32 percent more than the other hemisphere.

Use bubbles to reach the brain

Focused ultrasound was first approved in 2012 to relieve pain caused by cancer that has spread to the bone.

This technology, which is now going through various stages of development and testing for several medical conditions, involves delivering small microbubbles to the patient’s body through an intravenous line. The patient wears a special helmet that allows sound waves to be transmitted through his skull to specific locations in the brain. The locations are determined using magnetic resonance imaging machines. Sound waves to these tiny points cause the microbubbles to expand and contract, temporarily opening the blood-brain barrier.

Rezaei said that this technology has been used to help cancer treatments reach tumors inside the brain, but its application is more complex with Alzheimer’s patients, whose brains tend to be more fragile.

“I think it’s a very exciting pilot study and opens the door to more comprehensive research on the possibility of using focused ultrasound” to introduce lab-made antibodies and other drugs into the brain, said Eliezer Maslia, director of the National Center’s Department of Neuroscience. Institute on Aging, part of the National Institutes of Health.

Scientists are also exploring a second technique to bypass the blood-brain barrier, known as the “Trojan Horse” approach, Maslea said. The technique is named after the large wooden horse in mythology that the Trojans are said to have mistaken for a gift, so they took the horse inside their gates – along with the Greek warriors hidden in its belly.

In a pharmaceutical Trojan, researchers attach a drug to another molecule that recognizes a receptor in the blood-brain barrier. This receptor helps the drug cross the barrier and reach the brain. Another strategy called Transcytosis works like a relay race, where molecules deliver the drug to each other as if it were a baton.

The new study does not represent the first time focused ultrasound has been used on Alzheimer’s patients. Alzheimer’s patients participated In a 2018 study, though, they were given antibodies to treat cancer that had spread to the brain, not Alzheimer’s.

Previous studies using focused ultrasound without any Alzheimer’s medication have suggested that sound waves by themselves may provide a small benefit to patients. Rezaei said that the process activates the lymphatic system, which directs the brain’s immune response.

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Joshua Grell, a professor of psychiatry and human behavior at the University of California, Irvine, called the study “biologically very exciting,” adding that the research may help scientists understand why some Alzheimer’s drugs work better than others. Scientists want to understand, for example, whether the important factor is how low amyloid levels are, or how quickly they are eliminated.

Grill also He sounded a warning, saying that while focused ultrasound may increase the effectiveness of antibody treatment by allowing more of them to reach the brain, it may also greatly increase the severity of side effects. In the case of aducanumab, side effects can include seizures, nausea, confusion, and headache.

“We have a blood-brain barrier for really important reasons to protect our most important organ,” Grill said.

He stressed that years of work may have been needed before Focused ultrasound therapy could become an approved option for patients: “We’re not even close to that now.”

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