Alzheimer's patients treated with ultrasound to open the blood-brain barrier
Canadian researchers have taken a key first step that could potentially lead to a whole new way of treating Alzheimer’s disease.
The researchers from Sunnybrook Health Sciences Centre and University of Toronto are using focused ultrasound to safely open the blood-brain barrier in patients with Alzheimer’s disease, with the hopes this will help clear the brain of toxic plaque.
It’s an “out of the box” approach using patients like Karen Hellerman. The 62-year-old from Chatham, Ont. was diagnosed with early stage dementia.
Hellerman is losing her short-term memory and her ability to process complex tasks.
“Sometimes I can get it out, and sometimes I can’t and that disturbs me. “ Hellerman told CTV News. Her husband Neil knows there are no drug treatments to effectively slow or stop the disease.
“As her dementia gets worse, her physical state will get worse…it’s not a good thing. And she’s young, she’s gonna miss part of her life,” said Neil.
She is patient No. 3 in a group of six people with early Alzheimer’s disease, participating in the first study of its kind.
One of the biggest challenges in treating brain disease is getting drug therapies past the blood-brain barrier, which is like a protective “wrap” that surrounds even the tiniest blood vessels in the brain and acts as a “gate” to protect the brain from toxins and proteins that could enter through the bloodstream.
But it also hinders the entry of medications that could be effective in treating Alzheimer’s and other brain diseases.
In November, 2015, Sunnybrook researchers temporarily opened the blood-brain barrier for the first time to see if they could deliver chemotherapy directly into a patient’s brain tumour.
Now, researchers are using the same technique for Alzheimer’s patients.
This historic trial means that one day it may be possible to allow the entry of medications or even stem cells directly into the brain, which could be effective in treating dementia. The treatment could also help open the “gate” of the brain to allow the body's natural cleaning mechanism clear out the amyloid brain plaques that are the hallmark of Alzheimer’s.
For the procedure, a specialized helmet-like device was placed on Hellerman’s head and she was placed inside an MRI machine.
Then, microbubbles were injected into her vein, which travelled to the brain within 30 seconds. Ultrasound waves were sent to a small area of the brain to shake the microbubbles, temporarily opening the blood brain barrier.
Using contrast dye, the team was able to confirm right away the barrier had been opened and that it stayed open for about six to eight hours.
The team didn’t deliver any medications into Hellerman’s brain in the ultrasound sessions. Their goal was simply to investigate whether the barrier could be breached successfully and safely.
The motivation for the study is success in animal trials.
Researchers found the focused ultrasound helped to reduce the amyloid plaques in the brains of the mice.
What’s more, memory task testing showed that the mice’s memory greatly improved. The scientists were also able to look at slices of the brains of the mice, and found they had less amyloid plaque after the procedure.
Kullervo Hynynen, director of physical sciences at Sunnybrook Research Institute, has been working for two decades on the technology.
“It could be we are stimulating some effects in the brain that help it clear itself,” he said. “We also think we are stimulating growth of new neurons.”
It’s possible that by opening the barrier, the treatment is allowing the brain to naturally flush out toxic plaque.
Dr. Nir Lipsman, principal investigator of the trial and a neurosurgeon at Sunnybrook, said it suggested that focused ultrasound might not only attack the pathological hallmarks of Alzheimer’s disease, but there may be a hint there that it could tackle the symptoms as well.
The technique will be tested on five other patients with Alzheimer’s disease. All will undergo two sessions of focused ultrasound and various cognitive testing as well as imaging scans to see if there are any changes of amyloid deposits linked to AD in the brain.
Neurologist Dr. Sandra Black, the co-principal investigator of the new trial, says she is excited about the research but cautions it is early days. .
“It’s a whole new world of possibilities. But we have to take one step at a time and make sure it’s safe,” she noted.
If this phase proves successful, the researchers may begin another trial to test introducing small amounts of drugs into the brain area most affected by dementia, the hippocampus, which is the region for creating new memories.
Hellerman knows this first safety study won’t help her, but the knowledge gained will advance research.
“Maybe not for me, but for others…maybe better, you know what I mean,” she said.
Her husband hopes she will be on top of the list for future studies of focused ultrasound.
“My hope is that it works and that Karen’s level of dementia doesn’t get worse, and maybe gets better,” Neil said.
With a report from CTV medical specialist Avis Favaro and producer Elizabeth St. Philip