Testing targets dementia
Canadian researchers hope that focused ultrasound can revolutionize treatment
Karen Hellerman sits patiently in her hospital gown as Dr. Nir Lipsman gently shaves her head. The neurosurgeon then injects freezing into her newly shorn scalp before fitting her head with a circular frame, snugging the helmet-like device with screws so it can’t shift during the upcoming procedure.
The former elementary school teacher and principal from Chatham, Ont., has early-onset Alzheimer’s and has volunteered to take part in a bold, new experimental procedure at Sunnybrook Health Sciences Centre in Toronto — one which, doctors hope, may some day revolutionize the treatment of dementia and other debilitating neurological disorders.
Hellerman is then taken into the MRI suite where, for the next few hours, she lies sedated in the huge, noisy scanner as her brain is imaged and low-intensity ultrasound waves are passed through her skull, targeting the right frontal lobe of her brain.
The aim is to poke microscopic holes in the blood-brain barrier, a fine membrane that keeps “bad things out of the brain,” including disease-causing microbes, Lipsman explains.
“But it also keeps potentially good things out of the brain as well, including medical treatments for very common brainbased disorders, of which Alzheimer’s is a good example,” he says. “So what we have, therefore, potentially, are medical treatments that may work, but just cannot get into the brain in sufficient concentrations to have a good effect.”
Being able to breach the barrier should allow drugs to pass more easily into the brain, where they could deliver a much stronger therapeutic punch, Lipsman says. The Sunnybrook team has been testing MRI-guided focused ultrasound, as it’s known, in a small number of patients with brain tumours and, more recently, in those with Alzheimer’s.
But Lipsman stresses the studies are strictly aimed at establishing that the procedure is safe for patients — no treatment is given after the blood-brain barrier is opened, and it closes on its own in about six to eight hours.
Hellerman is the third Alzheimer’s patient to undergo the procedure, which took place on Tuesday. She had no hesitation about being a human guinea pig, even though she knows it may not be fully developed soon enough to help her condition. It could be years before patient trials prove the technique is a safe and effective means of enhancing drug treatment to diminish the amyloid plaque and protein tangles that progressively destroy brain cells.
“I’m not doing it for me. I’m doing it for other people,” says the 63-year-old mother of two grown children, although her husband, Neil, says he hopes “that maybe it will help you in the long run.”
Doctors at Sunnybrook have used MRI-guided focused ultrasound to treat a condition called essential tremor, in which a person’s extremities, particularly the arms and hands, develop uncontrollable shaking that can prevent them from performing the simplest of tasks, from eating and drinking to writing their name. In that case, high-intensity ultrasound waves destroy a tiny area of the brain where the tremor originates.
With this procedure, the ultrasound waves have a different role. They act by exciting microbubbles that are injected into the bloodstream, causing them to vibrate and tease open minute gaps between the cells that make up the blood-brain barrier.
“The way we do that is we expose the brain to pulses of lowfrequency ultrasound,” Lipsman says. “So with focused ultrasound, combined with these microbubbles, what we can do is open a temporary window in that bloodbrain barrier, permitting potentially therapeutic compounds access to the brain. “We view this as a significant advance towards overcoming a key obstacle for medical treatments.”
Dr. Kullervo Hynynen, director of physical sciences at the Sunnybrook Research Institute, developed the idea of pairing MRI with focused ultrasound while at the University of Arizona in the early 1990s. He has worked with industry partner InSightec of Israel for more than two decades to develop the technology.
“The long-term goal is to develop a technique where we can put any kind of molecules or cells in specific locations in the brain,” Hynynen says after watching images of Hellerman’s brain on computer screens outside the MRI suite, where a team of technicians had remotely triggered bursts of ultrasound waves through her skull.
Those molecules could include not only medications to slow down — or possibly even halt — the ravages of Alzheimer’s, but also chemotherapy agents for brain tumours and stem cells to repair the damage from a stroke.
In experiments performed on laboratory mice with the equivalent of human Alzheimer’s disease, Sunnybrook scientists were surprised to find that just opening the blood-brain barrier in the animals had an effect on plaque that had accumulated in their brains, even without the use of drugs.
“What we have seen in animals is that we can clear the plaques in the brain, so reduce the amyloidplaque load and improve the memory of animals and also stimulate new neuron growth,” Hynynen says.
“I think this technique will revolutionize how we are going to treat brain disease and maybe even enhance brain performance.
“This is a very first step for us. But if all goes well — it’s a long road — eventually this will be able to help millions of patients if it’s successful and safe.”