Researchers at Severance Hospital have confirmed that using an extensive frontal focused ultrasound to open the blood-brain barrier (BBB) of a patient can increase the efficacy of Alzheimer's disease treatment.
The team, led by Professors Chang Jin-woo of the Department of Neurosurgery and Ye Byoung-seok of the Department of Neurology, expects their research to help overcome Alzheimer's by increasing the drug delivery rate as the illness currently has no other treatment options than drugs.
According to the National Institute of Dementia, the number of dementia patients aged 65 and over in Korea totaled 840,000 last year, meaning that one in 10 people over 65 have dementia. About 70-75 percent of them suffer from Alzheimer's.
There is no other way to treat dementia other than drugs. Aducanumab is the only amyloid-removing drug approved by the U.S. Food and Drug Administration but has a limit to its efficacy. Hospitals also use other drugs to treat Alzheimer's, but they only slow down the progression of the disease.
One of the obstacles to using drug treatment for Alzheimer's patients is the BBB.
To protect the brain, the BBB accepts only molecules that regulate brain homeostasis and filter out the rest, which, in turn, reduces the delivery efficacy of the dementia drug.
To resolve this problem, the Severance team researched the safety and efficacy of the BBB opening procedure to increase the drug delivery rate for dementia.
The researcher used an extensive frontal focused ultrasound to open up the BBB of five patients with severe Alzheimer's twice at three-month intervals between March and August last year.
The surgery technique opens the blood-brain barrier in the frontal lobe by integrating ultrasound into the blood-brain barrier in the frontal lobe after injecting a contrast agent to the patient. It is the first time that a research team has used such a method in clinical practice.
Afterward, the patients took medication for six months, with the researchers conducting a positron emission tomography (PET) scan to check amyloid deposition before and after the procedure.
The research team calibrated the PET test values to determine the degree of amyloid reduction using the standardized intake coefficient rate and conducted a caregiver-administered neuropsychiatric inventory (CGA-NPI) survey for caregivers to determine the severity of dementia based on behavior and psychology.
As a result of the study, the standardized intake coefficient rate of the final test was 0.986 on average, which was 0.016 lower than the first test result of 1.002, indicating a decrease in amyloid.
The patient's problem behavior felt by the caregiver also improved as the CGA-NPI score dropped from eight to two.
Significantly, the team found no side effects in any participants during the study period, confirming the procedure's safety.
"Dementia is a representative disease that mankind has not conquered along with cancer because there is no proper treatment," Professor Ye said. "By allowing treatments to safely cross the BBB, which has been a major obstacle in using therapeutics, the team expects that the research will provide an opportunity to find a breakthrough treatment for dementia."
Professor Chung also said, "In a joint study with a research team from Seoul National University, the team has confirmed that combining aducanumab with the BBB opening surgery in a mouse model with dementia had better treatment effects, such as reducing amyloid in the brain, than using aducanumab as a monotherapy."
Therefore, the team is trying to find new antibodies with improved effects than aducanumab, Chung added.
Translational Neurodegeneration has published the results of the study.