Canadian researchers have launched a world-first study to fight ALS in an entirely new way, using a specially designed helmet that delivers medication into the brain using low-dose ultrasound.
The goal is to open the protective blood-brain barrier and unlock new treatment studies for this fatal neurological disorder.
“I think this is a very exciting day for the ALS community,” said Dr. Lorne Zinman, director of the ALS clinic at Sunnybrook Health Sciences.
“For the first time, we’re creating this temporary therapeutic window where our interventions have a chance of really making a difference in this awful disease,” added Zinman, who is a co-investigator in this landmark trial.
Bill Traynor didn’t hesitate to sign on as the first patient. The 70-year-old Toronto man was diagnosed with ALS last fall, sparking a devastating decline from his once active lifestyle.
“I always lived on the edge,” Traynor told CTV News. " Skydiving, scuba diving, skiing, and tennis, which was my big sport."
Now, he can’t use his hands much and needs a walker or two canes to get around. Medication for ALS hasn’t substantially slowed the trajectory. He says the study launched by a team at Sunnybrook Health Sciences gives him purpose.
“I told them, whatever you have, whatever you need, I’m there... I’ll do anything to help people cure this.”
ALS in Canada
Traynor is the first of six ALS patients with a sporadic form of the disease to join the study. Sporadic ALS is the most common, making up 95 per cent of cases in Canada. It has also been identified as an inflammatory disease, where some types of immune cells appear to mistakenly attack cells in the brain and spinal cord.
ALS, also known as Lou Gehrig’s, affects the nerve cells in the brain and spinal cord and leads to a loss of muscle control, resulting in paralysis, difficulty swallowing, and difficulty breathing. Eighty per cent of patients die within five years, with current medications unable to stop its progression. Some 4,000 Canadians currently live with this disease.
What does the study entail?
Patients in the study will undergo a two-part therapy.
The first is infusions of immunoglobulin, or IVIG. It’s a commonly used immune therapy for other diseases that helps reduce inflammation, and was tried in ALS in the 1990s, however, it had disappointing results. Scientists learned that less than a fraction of one per cent of the medication got into the brain.
“The blood-brain barrier... limits harmful toxins and infections from accessing the brain, which is a good thing, but the problem is, it blocks our most promising therapeutics in ALS to get access to the brain,” said Zinman.
That leads to the second part of this experiment.
It involves a futuristic-looking domed helmet, lined with some 4,000 transmitters that produce low-dose ultrasound signals. It is designed to temporarily open the blood-brain barrier in very specific regions of the brain, helping push more medication into areas affected by ALS.
“You can have very precise control of the exposures, and it’s tailored to the patient. Each location of the brain gets the right exposure, and there’s no other device that can do that,” said Kullervo Hynynen, a neuroscientist at the Sunnybrook Research Institute, who has spent the last 20 years working on its design.
The morning of his treatment, Trayner was placed into the helmet. The helmet was inside an MRI, for this first case to help doctors confirm everything was working as planned.
Eventually, the helmet will be used on its own.
The ultrasound treatment took less than 45 minutes, and scans showed tiny white spots, produced by a gadolinium marker, showing where signals from the ultrasound helmet had opened the blood-brain barrier. It happened precisely in the target regions responsible for leg and hand movement. It also means the medication given to Trayner is flowing into his brain.
“It’s there,” said Zinman, pointing to white spots in the brain MRI.
“(It) stays quite long in the tissue, like two to eight weeks,” said Dr. Agessandro Abrahao, who is a neurologist in the Garry Hurvitz Brain Sciences Program at Sunnybrook and an investigator in the trial.
He says patients will be tested to see changes in symptoms and levels of inflammation in the brain and spinal fluid.
“We’re going to confirm the biomarkers before and after (treatment), just to prove that we not only delivered, but that it also engaged in the biology,” he added.
The future is in the next room
The next generation ultrasound helmet hangs upside down, tethered with white cables to machinery. It is the prototype of a more portable brain ultrasound device that is under development. That’s because, according to Hynynen, ALS is just the start for this technology.
“This is designed to be used for any kind of brain conditions, to help in putting medicine in the brain,” he said.
There are plans to test the helmet, perhaps later this year, with chemotherapy delivery for glioblastoma, a deadly brain tumour that ended the life of Tragically Hip frontman Gord Downey.
Next on the list, scientists want to see if they can use it to help patients with Alzheimer’s Disease, either by driving medications into the brain or using higher frequency ultrasound without any medication, to change how the brain functions -- a newer field called neuromodulation.
“There’s a lot of excitement going on because of lots of brilliant new approaches,” said Dr. Andrew Eisen, a founder of the ALS Society of BC and professor emeritus at the University of British Columbia.
“To me, the most exciting one is the focused ultrasound, because you’re breaking the blood-brain barrier, and you’re able to do things, do things of depth which might be valuable.”
But the move forward is being done carefully, says neurosurgeon Nir Lipsman, who is Chief of the Hurvitz Brain Sciences Program and part of the study.
“Focused ultrasound still involves influencing ...highly delicate brain structures… we are investigating whether we can do these procedures safely.”
The first signs for Traynor are all good. Scans the following day showed the blood-brain barrier had closed back to normal.
Researchers will now be tracking him and the five patients who follow over the next five months before deciding if and how to expand this research.
Traynor admits there are no guarantees, but the study has given him purpose and has cut through the darkness of his diagnosis.
“I want to be able to walk... I want to be me,” he said. “There’s this light at the end of the ALS tunnel (and it went) from nothing to sunshine.”
