Dr. Agessandro Abrahao, MD, at the Sunnybrook Research Institute, awarded $125,000 over two years.
In the intricate network of the brain and spinal cord, neurons communicate with one another via specialized chemicals known as neurotransmitters. When this signaling network functions properly, a delicate balance is maintained between chemicals that stimulate (excitatory) and calm (inhibitory) neuronal activity. A hallmark feature of ALS, thought to occur even before symptoms appear, is that motor neurons in the brain become overexcited (or hyperexcitable). This change occurs at the cellular level and can’t be noticed by people experiencing it, but researchers have found evidence of hyperexcitability in both electrical recordings from the brain and markers in the cerebrospinal fluid of people with ALS.
To target and reduce this hyperexcitability, researchers have been studying repetitive transcranial magnetic stimulation (rTMS), a non-invasive brain stimulation technique that applies magnetic pulses to brain. A novel technique of rTMS is called accelerated continuous theta burst stimulation (cTBS), which produces a higher intensity of magnetic pulses over a shorter timeframe. This technique was first tested on the motor cortex of seven people living with ALS in an open-label pilot trial (called QuARTS-LAS) led by Dr. Abrahao and his team. They have demonstrated that the intervention was safe and well-tolerated, with a temporary trend of reduced abnormal hyperexcitability.
In this project, Dr. Abrahao and his team now aim to further explore the ability of cTBS to reduce abnormal motor cortex activity with a prolonged effect. They will recruit twenty participants living with ALS to undergo a cTBS dosing regimen for six months. Trial outcomes include assessing if the treatment is safe and tolerable, tracking biomarker changes such as NfL levels and ALSFRS-R scores, and other biological measurements to evaluate if cTBS can restore the normal neurochemical balance of the brain, potentially leading to a slowing of disease progression. The study will also explore if a protein called KCC2 can be used as a biomarker of hyperexcitability in people living with ALS, as the team has recently discovered that KCC2 levels are elevated in the disease.
Collaborators: Drs. Lorne Zinman, Sean Nestor, Robert Chen, Clement Hamani, Nir Lipsman, Kelvin Jones, Sahara Khademullah, Yves De Koninck, Janice Robertson & Jamie Near
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