ALS is a fatal disease where the brain can no longer signal the muscles because the microscopic living wires (cells called motor neurons) that connect them malfunction and die. This leads to a progressive paralysis where the individual loses the ability to move, speak, swallow and eventually breathe. To this day, we have no effective treatments, but there is tremendous hope in the research community that we are on the right track.
There is no better time in ALS research history for the ice bucket challenge to have captured the attention and generosity of Canadians. We are at a time of unprecedented momentum in our understanding of the disease and researchers have come further in the past half decade than in the previous century. When Lou Gehrig was diagnosed with ALS in 1939 and passed away two years later, scientists began focusing on ways to treat the fatal disease. As technology was limited, from the 1940’s to the 1980’s, much of the work done was observational in nature. By the 1980’s the possibility to identify genetic changes that could cause a hereditary (familial) disease became reality. Approximately 10% of ALS is familial and it has long been believed that identifying a gene that could cause ALS in one of these families, would give us a tool (the gene) to work with in the laboratory to make animal and cell models that mimic human disease, allowing us to both understand how it works and find new treatments. After years of work, the first genetic cause of ALS was discovered; a mutation (a tiny change) in superoxide dismutase 1 (SOD1) represented about 1/5 of the familial cases. This also meant there were many other genes to be discovered causing the other 80% of familial disease.
Scientists around the globe worked for the next 13 years trying to understand how SOD1 caused ALS, but it was like trying to solve a very complex puzzle with one puzzle piece. A lot was learned, but we needed more pieces if we were going to solve the puzzle. In the past 5-7 years, the massive acceleration in technology for identifying gene mutations has now provided most of the other genes that cause familial ALS, including three prominent ones that are responsible for significant portions of the families worldwide. In 2014, researchers are actively producing new models of the disease and working to understand how all of these new puzzle pieces fit together, and looking for mechanisms they have in common that might serve as targets for new therapies. In addition, other breakthroughs have come in identifying other cells (besides motor neurons) that actively contribute to the disease, discovering new ways to study the disease using models like worms and fish, and even being able to replicate human motor neurons in the lab using samples from people’s skin.
This means that you have many of the world’s best researchers believing we have a genuine shot at understanding ALS at the laboratory level in the foreseeable future, and that it is only a matter of time before this leads to a new generation of therapeutics to be tested in the clinic for slowing down the progression of ALS and providing a better quality of life for a longer period of time. As we work to coordinate therapies with earlier diagnosis, perhaps someday we can create a world without ALS. And all of this leads back to the generosity of. The key piece to accelerating ALS research is not the lack of ideas, but the resources required to execute all of the work that researchers are anxious to do. In a whole new world of increased awareness and funding, Canadians can be proud that their donations are going towards something that undoubtedly make a difference.
David Taylor, PhD
Director of Research
ALS Society of Canada
The following are videos to aid in understanding Research:
Dr. Christine Vande Velde is an Assistant Professor at CHUM-Université de Montréal. She is an expert on understanding the mechanisms underlying ALS. In particular, she has focused her work both on the energy producing structures in cells called mitochondria, and their involvement in the disease, as well as understanding the function of structures called stress granules in ALS. Dr. Vande Velde is the lead investigator on a 2015 ALS Canada-Brain Canada Arthur J. Hudson Translational Team Grant.
Dr. Alex Parker is an Assistant Professor at CHUM-Université de Montréal. Dr. Parker is an expert in neurodegenerative disease research using worms called C. elegans as models. He has several worms that mimic ALS and these are used to better understand how the disease is caused and to screen for potential treatments. Dr. Parker has been successful in attaining a number of grants through ALS Canada Research Program competitions. Most recently, he received a 2014 ALS Canada-Brain Canada Discovery Grant.
Dr. Cashman is a neurologist, professor and researcher at University of British Columbia. He is a world leader in understanding the mechanisms by which SOD1 misfolding may propagate disease through cells and the body in both familial and sporadic ALS. He is also actively examining misfolding mechanisms of other ALS proteins and how they interact with SOD1. Dr. Cashman has been successful in attaining a number of grants through ALS Canada Research Program competitions. In 2015, he received a 2 year Bridge Grant.
Dr. Lorne Zinman, Director of the ALS Clinic at Sunnybrook Hospital in Toronto and Chair of the Canadian ALS Research Network (CALS), discusses his clinic, his research, CALS and the importance of the WALK for ALS.
Dr. Sanjay Kalra, a neuroimaging expert at University of Alberta, discusses his work on using novel techniques to understand brain degeneration in ALS and to determine how that might aid in diagnosis of the disease.
Dr. Yana Yunusova, a speech-language pathologist at University of Toronto, discusses her clinical research focused on better understanding mechanisms of diagnosis and prognosis in individuals with bulbar ALS.
Dr. Michael Strong, a pioneer in ALS research with more than 20 years’ experience, comments on where your donated dollars go in research and the achievements of his lab at Western University.