From Inquiry to Insight: Dr. Michael Strong

Updated October 20, 2017

Dr. Michael Strong has spent his career as a clinician scientist researching ALS with a determined curiosity and keen attention to new learning in the field. Over the years, people living with ALS and their families have been an ongoing source of inspiration to him. “The toughest thing in life is to diagnose someone with ALS because there is so little we can do to stop the disease,” said Dr. Strong in an interview with ALS Canada. “But people and families living with ALS are the most rewarding group to work with. It’s a real privilege that I absolutely enjoy.”

Career Signposts

Several events in his early training led to Dr. Strong’s decision to focus on ALS. As part of completing his medical degree at Queen’s University in Kingston, Ontario, he decided to do an elective placement with a neuromuscular group in Copenhagen, Denmark. Before departing overseas, he examined a person with ALS in a hospital setting and thought that would be his last opportunity to see someone with the disease. As fate would have it, his placement in Copenhagen turned out to be the only ALS treatment center in Denmark, which gave Dr. Strong the opportunity to learn from many more patients as well as clinicians.

When Dr. Strong returned to Canada, he completed his neurology training at Western University in London, Ontario, under Dr. Arthur J. Hudson, a co-founder of ALS Canada. “Both Arthur and the neuropathologist recognized that I had a real interest working in neuropathology, allowing me to do a lot of work that residents wouldn’t normally get a chance to do,” said Dr. Strong. Neuropathology is the scientific study of brain and spinal cord tissue to understand disease processes.

After he had heard Nobel Prize winner Dr. Carleton Gajdusek from the National Institutes of Health (NIH) in the United States present findings on a particular form of ALS that occurred with a much higher prevalence in a Western Pacific region, Dr. Strong was intrigued. He went to the NIH to complete a post-doctoral fellowship in ALS and then returned to Western University to continue working in the field.

Today, Dr. Strong is Dean of the Schulich School of Medicine & Dentistry, Distinguished University Professor in the Department of Clinical Neurological Sciences and holds the Arthur J. Hudson Chair in ALS Research at Western University. He also maintains a clinical practice focusing on diagnosing and treating people with ALS. One of his key areas of research over the years has been to explore the relationship between ALS and frontotemporal dementia. ALS Canada has provided past funding for Dr. Strong’s work in this area.

Inquiries to Insights: Frontotemporal Dementia in ALS

Frontotemporal dementia is a group of disorders caused by nerve cell loss in the frontal lobe of the brain, which plays a large role in voluntary movement and cognitive functions including decision making and speech, or the temporal lobe, which is responsible for processing sensory input. While the association between frontotemporal dementia and ALS is distressing, Dr. Strong believes that people and families facing an ALS diagnosis need to be aware.

“It’s a big relief for patients, families and caregivers to know that dementia-associated behaviours are not their fault but are a result of the disease,” explains Dr. Strong, who notes that the association between ALS and frontotemporal dementia has recently led to the identification of 4 drug targets that may benefit lots of people in the future.

In the early 1980s, it was believed that dementia in ALS was exceedingly rare, occurring in about 15 per cent of cases. Dr. Strong, however, found that conclusion at odds with what he and others were seeing in the clinic: that one in four people with ALS had problems controlling their emotions, such as experiencing spontaneous laughter or tearfulness, which suggested that a form of dementia might be associated with the disease. Dr. Strong brought together a group of colleagues and published the first paper that challenged the assumption that there is no dementia associated with ALS.

Following that insight, he and his team investigated further. They knew from other scientists’ published work that one of the problems sometimes associated with ALS is a decline in the ability to form words, a process called verbal praxis, where the brain makes the connection between thoughts and speech. Using an advanced imaging technique called magnetic resonance (MR) spectroscopy, Dr. Strong and colleagues examined post-mortem tissue and found that people with ALS who had developed frontotemporal dementia had lost neurons in the same area of the brain responsible for verbal praxis.

After a further series of investigations, Dr. Strong and his team of researchers discovered that the underlying culprit is the deposition of tau protein. Normally, tau is critical for maintaining the structure of a neuron, but when harmful cell mechanisms release it, and it becomes free-floating, it can clump and form tangles that cause interruptions in neural pathways. “We published a paper showing that there is a very specific pathology with tau protein. For the last 15 years, we have been proving the change we saw in tau is not an accident. We know exactly what that change is and how it triggers neurons to die,” said Dr. Strong.

“Today, we know that some form of frontotemporal dementia in ALS is very common. The full spectrum includes mild impairment that may not be noticeable or cause problems, dysfunctional frontotemporal syndrome with behavioural or cognitive impairment, and full dementia, which affects about 15 percent of cases. All of those pooled together are found in well over half of ALS patients,” said Dr. Strong. This learning is critical since people with ALS who exhibit behavioural or executive functioning difficulties, such as issues with planning, reasoning and problem solving, have a least a year less survival time. Moreover, he added, “We know exactly what causes tau protein deposition. We can reproduce it and we have identified four different drugs that can completely stop the process.”

Dr. Strong and colleagues recently published a paper describing how the tau protein mechanism occurs in ALS as well as other dementias that involve excessive deposits of tau protein, including Alzheimer’s disease, vascular dementia and Parkinson’s disease.

Soon, a large, Canadian multicentre trial investigating similarities and differences in five neurodegenerative diseases known for tau protein deposit issues, will report on results. Dr. Strong is primary investigator of the study, called the Ontario Neurodegenerative Disease Research Initiative (ONDRI), which involves more than 50 investigators at 13 clinical trial sites and 600 participants. The diseases under investigation are ALS, Alzheimer’s disease/mild cognitive impairment, Parkinson’s disease, frontotemporal lobar degeneration and vascular cognitive impairment (from a stroke). ALS Canada is one of four patient advocacy groups serving in an advisory role.

Dr. Strong’s relentless work moving from inquiry to insight and repeating that process throughout his career has produced a series of new scientific discoveries in the ALS field. “It’s about doing experiments at the right time: paying attention to things changing in the field; listening to world experts; and every once in a while, walking away and saying, ‘Hmmm…maybe we’re wrong. Maybe we should be looking at this instead.’”

Dr. Strong acknowledges the important role that donors play in making ALS research possible, noting that in 1993 there were only a few researchers in Canada funded to work on ALS. “The transformation in ALS research led by ALS Canada over the last decade has provided a solid foundation for ALS research funding,” he says, “so investigators like myself know we have multi-year funding to move forward.”

ALS Canada Virtual Research Forum

Update: Dr. Michael Strong was one of more than 20 speakers who participated in the ALS Canada Virtual Research Forum in August. You can listen to his full presentation online here.

During his presentation, Dr. Strong provided an overview on frontotemporal dementia in ALS. Two messages he hopes people with ALS will take away from his talk are:

• Frontotemporal dementia with ALS is far more common than previously thought. People living with ALS need to be aware of how dementia affects their prognosis. Families and caregivers benefit by understanding that dementia is related to the disease, not to the care they provide.
• This knowledge is providing critical information about the biology of ALS that will guide the development of future treatments.