Focused Ultrasound Shows Promise in Delivering Drugs to ALS-Affected Brain Regions
A Milestone in ALS Treatment Research
Researchers at Sunnybrook Health Sciences Centre have achieved a meaningful milestone in the fight against amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig’s disease. In a Phase 1 clinical trial, they successfully used focused ultrasound to temporarily open the blood-brain barrier and deliver immunoglobulin directly to the motor cortex of an ALS patient.
Did you know? The blood-brain barrier is a highly selective membrane that protects the brain from harmful substances but also blocks potentially therapeutic drugs.
Dr. Lorne Zinman, neurologist and director of the sunnybrook ALS clinic, described the achievement as a major milestone.
He expressed excitement about the future, stating, Now that we have the capability of opening up the blood-brain barrier to exactly target where ALS starts, I’m really excited about the future.
The First Patient: Bill Traynor
Bill Traynor, 70, became the first ALS patient in the world to receive a drug via non-invasive ultrasound waves. He is the first of six participants in the trial, which aims to determine the safety of this novel drug delivery method.
Traynor’s journey began about 10 months prior when his ex-wife noticed an issue with his gait. She said,‘Bill,your right foot is kind of like slapping the ground.’ And being a guy, I said, ‘Nah, it’s nothing. It’ll go away.’
Unfortunately, it did not, leading to his ALS diagnosis and eventual participation in the groundbreaking trial.
Despite the challenges, traynor remains optimistic. It’s kind of exciting to be a guinea pig,
he said, viewing the study as a source of hope.
How Focused Ultrasound Works
The procedure involves several key steps:
- Immunoglobulin Infusion: Traynor received an intravenous infusion of immunoglobulin, an antibody therapy aimed at suppressing inflammation.
- Microbubble Injection: He was also injected with microbubbles.
- Focused Ultrasound Helmet: A helmet, developed by Sunnybrook scientist Dr. Kullervo Hynynen, was placed on Traynor’s head. This helmet contains 4,000 transducers that deliver focused ultrasound waves.
- Blood-Brain Barrier opening: The ultrasound waves cause the microbubbles to expand and contract in the small blood vessels of the targeted area, temporarily opening the blood-brain barrier.
- Real-Time Monitoring: Traynor was placed inside an MRI machine to allow the research team to monitor the procedure in real-time, ensuring the ultrasound targeted the correct brain region.
Pro Tip: Future trials aim to eliminate the need for MRI by personalizing the ultrasound helmet for each patient, pre-setting target points based on their individual brain structure.
Dr. Agessandro Abrahao, co-lead investigator and Traynor’s neurologist, explained the importance of this approach: The blood-brain barrier is there to protect us, so it keeps viruses, bacteria (and) toxins outside the brain.
However, it also blocks access for potentially life-saving drugs. Temporarily opening the barrier is a crucial step, ensuring it closes after drug delivery.
The Significance of Immunoglobulin
Immunoglobulin was chosen for this trial due to it’s anti-inflammatory properties.Dr.Zinman explained, We certainly know that the immune system is not normal in ALS. We know that it shifts to sort of a pro-inflammatory state where the immune system is assisting in the destruction of these motor neurons.
While previous trials of immunoglobulin in the 1990s showed no effect,researchers believe the drug did not have a fair chance because less than 0.01 per cent of a dose can cross the blood-brain barrier and reach the motor cortex,
according to Dr. Zinman.
Looking ahead: Future Trials and Hope
The researchers emphasized that this is an early-stage trial and will not promptly result in an ALS treatment. Larger,later-stage trials are necessary. Though, this step is crucial for testing various promising drugs.
Dr. Zinman poignantly described the urgency of their work: ALS is a horrible, terminal, incurable neurodegenerative disease that results in the progressive decline of motor neurons in the brain and spinal cord.
He added, Sadly, we have about three or four deaths a week in our clinic alone, and it’s awful. Literally, thousands of patients have died on my watch. And I think about that every day and how we haven’t yet had major interventions to change that.
Researchers will analyse Traynor’s blood and cerebrospinal fluid for biomarkers of inflammation to assess the immunoglobulin’s effect. While cautioning that this trial is not a treatment, they remain hopeful about the potential for future breakthroughs.
