More Than Microscopes: THE DIFFERENCE CANADIANS MAKE SAVING LIVES THROUGH MEDICAL RESEARCH

healthpartners.ca 150 YEARS … 150 MEDICAL RESEARCH ADVANCES … $150 MILLION RAISED: Canadian Researchers Make a Mark Here — and Around the World

Rick Perciante, Chair, Eileen Dooley Board of Directors CEO, HealthPartners HealthPartners

Pablum to improve infant nutrition. The ability of Without a breakthrough using stem cell-based T-cells to destroy bacteria and viruses and marshal therapy to treat aggressive forms of relapsing- the immune system. The Cobalt-60 ‘bomb’ to remitting multiple sclerosis, Jennifer Molson kill cancer cells. Controlled gene mutation. The wouldn’t have been able to participate in a link between stress and disease. Insulin to treat bone marrow transplant trial, which essentially diabetes. Child-resistant medical containers. transformed her life. Without ground-breaking Discovery of stem cells. drug therapies, eight-year-old Kaiden Ames would probably not be alive today, and his Despite an overall population of fewer than parents wouldn’t have the chance to see him 40 million, Canada has nurtured a striking number grow up and even be a parent himself. Without of scientists and researchers whose breakthrough deep brain stimulation surgery, Herb Durand medical discoveries — and their ongoing wouldn’t be able to fulfill a long-time dream: to contributions to medical knowledge — have hold his grandchild. And without the tremendous improved, or have the potential to improve, the strides that have been made in diabetes research, health of millions of people around the world, not Dwayne Vermette certainly wouldn’t be living a just across our vast country. healthy lifestyle after being diagnosed with type 2 diabetes in his 30s — including having the ability HealthPartners is proud to play a leadership role to manage his condition with pills rather than a in connecting donor dollars to life-enhancing and daily injection of insulin. life-changing research that makes a real difference in the health of Canadians. Given that nine out Our scientists have not only changed the lives of of 10 of us, living in neighbourhoods across this thousands of Canadians like Jennifer, Kaiden, Herb country, are touched by a major disease or chronic and Dwayne; they’ve made a mark internationally. illness, the value of the research that our member They’ve ushered in the age of modern nuclear charities support — thanks to the generosity of medicine, opened up the field of biotechnology, our donors — cannot be underscored. pioneered cell-based therapy, designed medical equipment, invented new surgical and treatment And our donors have been incredibly generous. techniques, developed drugs and vaccines, The $150 million raised through HealthPartners, and more — collecting seven Nobel prizes in coupled with other direct donations to our the process. charities, have given legions of Canadians support, dignity, hope — and even their lives. In terms of the amount of money we spend on research, we may rank 14th among 31 Western Through the pages of More Than Microscopes, industrialized nations, but we rank 6th in the we’ve chosen to highlight 150 achievements quality of our research. When it comes to world- that have advanced the field of medical research. changing research, Canada truly does punch These achievements are among hundreds that above its weight. have helped to move the research yardstick forward — and in the process, improving lives, Research excellence speaks to a culture that transforming lives and saving lives. supports innovation — to go where no-one has gone before. They also serve to showcase the tremendous research that is being undertaken by researchers In the area of medical innovation, HealthPartners’ and scientists who are supported by our 16 member health charities play a major role 16 member health charities. Their ground- in nurturing our country’s innovative research breaking and ground-blazing work is a cause culture. Through annual funding commitments, for celebration — and a concrete testament to our charities support the ability of researchers what can be achieved when Canadians lend from coast to coast to coast to exercise their their support to medical research. Through the creative research muscle. With scientific curiosity incredible support of donors to HealthPartners and intellectual know-how, these researchers and our charities — $150 million raised and delve into uncharted territory, propelled by a counting — we truly can achieve so much when it desire to save lives. And they do. comes to helping Canadians live healthy lives.

Here’s to the next 150 years! 2,500 to 3,000 Canadians over ALS Research the age of 18 have ALS First described in the 19th century, ALS, or amyotrophic lateral 2 out of every 100,000 people sclerosis, is a disease that gradually paralyzes the body, leaving people diagnosed with ALS every year without the ability to move, talk, swallow and eventually, breathe. Most people die within two to five years of being diagnosed with ALS 80% of people who have ALS because the disease has no effective treatment or cure. die within 2 to 5 years of their diagnosis However, ALS research has made more progress in the last 5 to 7 years than in the last century, advancing to a point which many ALS research experts believe effective treatments are now a matter of ‘what’ not ‘if.’

NIGEL VAN LOAN Nigel Van Loan’s wife, Patricia, passed away in 2007 from ALS, a terminal neurodegenerative disease that also took the lives of her mother and three sisters. Although she was relieved to have a diagnosis, she was overcome with fear, dread and panic — “I really didn’t know how I could live with ALS without going mad,” she wrote on the ALS Canada website. Patricia was able to live at home until her death thanks to the progress that had been made in ALS research into equipment loaned by the Society that kept her mobile, was used to transport her up and down the stairs, and enabled her to shower, bathe and get out of bed. After Patricia’s passing, Nigel became active in ALS Canada and remains a member of the ALS client services committee, lobbying the government for research dollars and fundraising for the Society as a way to keep his wife’s memory alive — and because ALS is in his family (his two sons and his grandchildren could carry the gene). Research Advances Through the Years: Highlights 2008: Stefano Stifani uncovers a key mechanism involved in the development of motor neurons, Canada is considered a leader in ALS improving our understanding of what goes wrong in neurodegenerative diseases such as ALS. research — consistently in the top five countries for ALS discoveries. Nicolas Dupré is part of the team that discovers the gene TDP-43 is involved in ALS.

2012: Michael Strong and his team discover a Current research studies include: new gene responsible for hereditary ALS. • replacing bone marrow cells with new cells containing potentially protective genes 2014: Michael Strong demonstrates that a large • as part of the first large imaging study in the number of miRNA are altered in ALS. world, exploring advanced MRI methods that can be used as a biomarker, making it possible Researcher Spotlight for physicians to detect the disease earlier, Robarts scientist and neurologist monitor disease progression and evaluate Michael Strong is a world leader new therapies in the search for a cure for ALS. • studying whether the most common genetic He balances his research work abnormality in ALS, which occurs in the with frontline clinical care of C90RF72 gene, causes or contributes to patients affected by the disease, the disease working with one of the largest research-based • studying the role of interneurons, which ALS clinics in Canada. Dr. Strong’s relentless work connect to motor neurons in the brain, in the moving from inquiry to insight and repeating that early stages of ALS process throughout his career has produced a series of new scientific discoveries in the ALS field.

Founded in 1977, ALS Canada and its provincial partners are dedicated to supporting Canadians living with ALS and investing in research to make ALS a treatable, not terminal, disease. Through the ALS Canada Research Program, ALS Canada funds peer-reviewed research grants, fosters collaboration and builds capacity within Canada’s ALS research community, and participates in new areas of research. Since 2014, ALS Canada has invested approximately $20 million into ALS research. The Society also supports Project MinE, a multinational initiative involving more than 15 participating countries, where the goal is to establish a global resource of human data that will enable scientists to understand the genetic signature that leads someone to develop ALS. The Canadian component of Project MinE brings together four of Canada’s leading ALS geneticists — Ian Mackenzie, Vancouver; Ekaterina Rogaeva, Toronto; Guy Rouleau, Montreal; and Nicolas Dupré, Quebec City — for their first ever cross-country collaboration. 564,000 Canadians live Alzheimer’s Disease Research with dementia By 2038, over 1 million Canadians will be living with dementia, largely 25,000 more Canadians are because the baby boom generation will have reached old age. diagnosed every year We still don’t understand exactly how Alzheimer’s disease damages 937,000 Canadians will have the brain — somehow cells are damaged and eventually die in dementia in less than 15 years different areas of the brain. The death of brain cells leads to dementia, For every person with dementia, characterized by memory loss, impaired judgment and behavioural 1 or more family members changes. But what we do know is that Alzheimer’s usually affects provide care at least two lives: the person with the condition, and the person’s spouse or child, who gradually becomes a full-time caregiver as the disease progresses. On June 22, 2017, Canada became Because there is currently no cure for Alzheimer’s, treatment focuses the 30th country to launch a national on relieving symptoms and maintaining the quality of the person’s life. dementia strategy. Research Advances Through the Years: Highlights 1993: Judes Poirier discovers that apolipoprotein E is a genetic risk factor for Alzheimer’s disease.

1995: Peter St George-Hyslop discovers and clones two genes responsible for early-onset Alzheimer’s.

MYRA CONWAY Dementia isn’t just an “old person’s disease”; it can affect younger people as well. Myra Conway’s husband, Michael, was diagnosed with Alzheimer’s at the age of 57, while still working full-time in the federal public service. While there is no cure for Alzheimer’s, research advances into this disease and other dementias have improved the quality of life of people with the disease and their caregivers. Providing valuable information on what to expect in terms of behavioural and cognitive changes, physical support, and caregiving and health service delivery proved invaluable for Myra as she navigated the disease journey with her husband. 2000: Peter St George-Hyslop develops a vaccine Alzheimer’s disease, as well as the SORL1 gene that prevents Alzheimer’s disease in mice and associated with common late-onset forms advances our understanding of dementia. of Alzheimer’s.

2001: Fritz Lorscheider discovers that mercury 2017: Weihong Song shows that vitamin A destroys nerve cells and may lead to the deficiency, even as early as in pregnancy, can affect development of Alzheimer’s. brain development and may facilitate Alzheimer’s.

2005: Vladimir Hachinski determines that “silent” Researcher Spotlight strokes can lead to dementia, including Alzheimer’s. Endel Tulving has had the greatest impact of any single 2006: Joanne McLaurin, Peter St George-Hyslop scientist on the understanding and David Westaway stop the build-up of toxic of human memory. A Canadian plaque in mice with Alzheimer’s, essentially curing icon and major international the disease. figure in experimental psychology, his theories have provided the Ian Mackenzie and Howard Feldman discover the foundation for the whole field of memory research. genetic cause of early-onset dementia. Tulving’s work led to an increased understanding of neurological disorders such as Alzheimer’s disease. 2011: Sylvie Belleville demonstrates memory In 1972 he introduced, and later elaborated on, training can help increase brain plasticity and the theory of “episodic memory.” Now generally reduce symptoms of Alzheimer’s. accepted, this theory has played an important role in the evolution of the concept of multiple memory 2012: Teresa Liu-Ambrose demonstrates that systems. Dr. Tulving was named an Officer of the resistance training may help people who already Order of Canada and is a member of the Canadian have a condition known as mild cognitive Medical Hall of Fame. impairment delay the onset of dementia. Current research studies include: 2016: Scientists identify a new syndrome they • looking at the role of Chma5 neurons in call “mild behavioural impairment,” which they treating Alzheimer’s believe is a precursor to Alzheimer’s or other types • preventing synapse loss and preserving of dementias. synaptic connections • using FNDC5/irisin as a novel Ekaterina Rogaeva discovers two genes responsible therapeutic approach for the most aggressive form of early-onset

Since its inception in 1978, the Alzheimer Society of Canada has allocated $53 million to research. Its research program falls into two types: the science of the brain, the changes that are associated with dementia and therapeutic targets to reverse, stop or cure the disease (biomedical research); and issues that impact the lives of people with dementia and their caregivers (quality-of-life research). Specifically, research has helped to: • identify potential new drugs for Alzheimer’s • develop neuroimaging techniques to distinguish different forms of dementia • determine how diet and other lifestyle choices may delay the disease • develop technology to enhance quality of life, care and safety for people affected • improve care delivery in the community and in long-term care settings 4.6 million Canadians aged Arthritis Research 15 years and older have arthritis The over 100 different types of arthritis fall into two main groups: 56% are under 65 years of age • osteoarthritis, caused by a breakdown of cartilage in joints, causing bones to rub together 1 in 1,000 children has arthritis • inflammatory arthritis, caused when the body’s own immune 1 in 10 adults has osteoarthritis system attacks healthy joints and tissues, causing inflammation and joint damage 80% of people with arthritis also have other chronic conditions

BLAKE KNOLL People with arthritis rely on a range of medications to manage and treat their symptoms. One class of medicine called biologics proved to be a life saver for a young hockey player, Blake Knoll, who spent every day in excruciating pain until he started an infusion every 2 weeks. By the second dose, he noticed substantial improvements, and by the third and fourth doses, he felt “normal” again. The medication is also making it easier for Blake to maintain his weight — which was a struggle when he was taking other medications. While there is no cure for arthritis, advancements in research have led to: Canada is a world leader in • more effective medications arthritis research. • better diagnosis of lupus and fibromyalgia • control of gout, rheumatic fever and infectious arthritis • reduction in hospital stays from months to weeks for the severely ill Researcher Spotlight • development of artificial joints to replace those A leader and innovator in totally destroyed by arthritis orthopedics, Robert Salter’s innovative research related Research Advances Through the Years: Highlights to the musculoskeletal 1925: James Collip discovers the parathyroid system has contributed hormone, which leads to better understanding to the understanding and of how the body regulates calcium and the prevention of degenerative arthritis, among other development of new treatments for osteoarthritis. musculoskeletal disorders. Through his research, Dr. Salter demonstrated that continuous motion 1961: Harold Copp discovers calcitonin, a after surgery stimulated the formation of new hormone that inhibits the release of calcium from cartilage, ultimately facilitating joints to heal the bones, used to treat osteoporosis, Paget’s properly and significantly reducing the likelihood disease of bone and rheumatoid arthritis. of the patient developing arthritis. This ground- breaking discovery helped change the treatment 2013: Chris Overall discovers that the protease and care of orthopedic surgery patients and in MMP2 can remove a block, thus allowing the prevention of degenerative arthritis due to inflammation to become activated. This pathway surgical trauma. is often overactive in patients with arthritis and other inflammatory diseases. Current research studies include: • investigating markers to predict who will get 2015: A McEwen Centre for Regenerative arthritis before symptoms start Medicine research team generates cartilage • researching new treatments for osteoarthritis tissue from human stem cells, which may make it pain and inflammation possible to eventually generate new cartilage to • looking at the role that the nervous system cushion joints. plays in arthritis • improving the delivery of care for Canadians suffering from arthritis of the spine and joints • evaluating a new model of care with arthritis and other forms of chronic pain in First Nations communities

Founded in 1948, The Arthritis Society has funded over $195 million in research projects — which have led to breakthroughs in the diagnosis, treatment and care of people with arthritis. In addition to individual research grants, the Society also supports arthritis centres, which are located in academic rheumatology divisions in Canadian medical schools, including accredited pediatric rheumatology centres. These centres provide exemplary patient care, high standards of graduate and undergraduate teaching, and excellent opportunities for clinical and basic science research. Cancer isn’t just one disease. It is more than 100 diseases, many of which are divided into several sub-types. In Canada, it mostly affects people aged 50 and older, but can occur at any age. Lung, breast, colorectal and prostate cancer are the most commonly diagnosed cancers in Canada, excluding non-melanoma skin cancer Nearly 1 in 2 Canadians expected to be diagnosed with cancer in their lifetime and 1 in 4 will die of the disease Estimated that in 2017, 206,200 Canadians will be diagnosed with cancer and 80,800 will die from cancer Leading cause of death in Canada — responsible for 30% of all deaths

KIM GURTLER Kim Gurtler has lost four people she loved to cancer. First, her two aunts, who were living across the country, were diagnosed with the disease and then passed away. Then, two close friends, both in their 30s, died from cancer. As if that wasn’t enough to deal with emotionally, soon after Kim faced her own cancer diagnosis. During a regular checkup at her doctor’s office, this healthy, active mother of two found out she had a malignant form of melanoma, called spitzoid melanoma. “My whole world turned upside down in a split second,” she says. But after the usual feelings of self-pity and self-reflection, Kim decided to get on with life, glad that it was she and not her husband and children who got the disease. She knows the odds of surviving a melanoma skin cancer — on average, about 88% of people with this type of cancer will survive for at least 5 years — and is making every day count by helping others with cancer live well. Cancer Research We know more about what causes cancer, how Cancer research in Canada continues to it develops, how best to treat it and how we can improve the quality of life of people living move us closer to the day when many with cancer. Thanks mainly to strides in cancer cancers will be curable and others will research — in prevention, early detection and be managed as chronic diseases like treatment — the overall cancer survival rate diabetes and asthma. has increased from about 25% in the 1940s to nearly 60% today. Some cancers, like thyroid and testicular, now have a five-year net survival rate of over 90%.

Research Advances Through the Years: Highlights 1965: Phil Gold and Samuel Freedman discover 1951: Harold Johns develops the Cobalt-60 carcinoembryonic antigen. Because of this, a unit or “Cobalt Bomb,” which becomes the most blood test can be used to help detect cancer early effective cancer treatment and begins the modern or monitor the effectiveness of treatment. era of radiation therapy. 1970s: Anthony Miller evaluates the effectiveness 1956: Vera Peters pioneers the use of radiation to of Pap test screening as a way to reduce the treat Hodgkin’s disease. number of Canadian women dying from cancer of the cervix. 1958: Research funded by the Society leads to the discovery of vinblastine by Robert Noble 1973: Frank Graham inserts extra copies of genes and Charles Beer, which is still used to treat into mammalian cells — a big step forward in the many cancers. development of cancer gene therapy.

1961: James Till and Ernest McCulloch discover 1976: Victor Ling finds that P-glycoprotein stem cells in bone marrow, which leads to the causes cancer cells to become resistant to development of bone marrow transplantation as a chemotherapy drugs. life-saving treatment for many cancers.

First formed in 1938, the Canadian Cancer Society is the only national charitable organization that supports all Canadians with all cancers in all communities across the country by taking a comprehensive approach by: • funding high-quality cancer research • educating Canadians about cancer prevention, screening and early detection • providing information and support services for patients and their families • taking a stand on important cancer issues and influencing government to pass public policies aimed at preventing cancer and helping people living with cancer Since 1947, the Society has funded over $1.2 billion in cancer research, including $40 million in leading-edge work supporting more than 340 projects across the country in 2016–17. The research the organization funds covers a wide range of work that can be applied to many types of cancer. Funding is split as follows: • quality-of-life research to study things like survivorship, end-of-life and supportive care — 9% • prevention — 16% • basic, biomedical and translational research to better understand how cancer grows and spreads, and studies on diagnosis, treatment, screening and early detection — 75% Researcher Spotlight: Harold Johns 1984: Tak Mak clones a white blood cell gene known as a T-cell receptor gene, helping to shape the field of immunotherapy and cancer vaccines.

1986: Anthony Pawson discovers that a specific protein molecule can be used to transmit signals within cancer cells. Understanding how cells “talk” to each other helps establish a new research area in targeted therapies.

1990s: Helen Chan and Robert Phillips discover that retinoblastoma, a cancer of the eye, arises in children when the RB1 gene is mutated. Doctors can now test for RB1 to diagnose and treat cancer earlier.

Steven Narod shows that women who inherit specific mutations in the BRCA1 gene are at increased risk of developing breast and ovarian cancer.

1994: John Dick and his team isolate cancer stem cells.

1995: Patrick Lee discovers that the reovirus can seek out, infect and attack cancer cells without harming normal cells.

Building on this discovery, Peter Forsyth and others study how oncolytic viruses can be used to kill or shrink tumour cells.

2000s: A Canadian Cancer Trials Group clinical trial finds that women who took letrozole after tamoxifen therapy had a greatly reduced risk of the cancer returning — changing the way breast cancer is treated worldwide.

Mick Bhatia discovers how stem cells can be triggered to become blood cells, paving the way for new therapies for leukemia.

Eduardo Franco and several international scientists pinpoint human papilloma virus (HPV) as the cause of cervical cancer. The HPV vaccine, approved in 2006, is helping prevent HPV cancers for thousands of people worldwide. 2006: John Dick finds a way to destroy leukemia 2016: Canadian surgeons are first in the world to stem cells responsible for its recurrence. relocate the thyroid gland of cancer patients to their arm. 2010s: David Malkin develops a method to catch cancers early in people with Li-Fraumeni Researcher Spotlight syndrome, a rare inherited disorder that increases Harold Johns was a trailblazer in the fight against cancer susceptibility. The screening method has cancer. Funded by the Canadian Cancer Society, been adopted around the world, and people he was influential in the early development of who participate have dramatically higher cancer computed tomography (CT) scanners and medical survival rates. imaging. His ground-breaking Cobalt-60 machine, which had an immediate positive impact on Michael Taylor discovers that medulloblastoma, patient outcomes, allowed for radiation treatment the most common form of childhood brain of tough-to-reach tumours. This was a pivotal cancer, is not one disease but rather four different advancement in the fight against cancer. For his subtypes with distinct molecular features and achievements, Dr. Johns was named a member of clinical outcomes — helping to refine treatment the Order of Canada. and spare young patients from unnecessary side effects. Clinical trials help find new methods for diagnosing, treating, managing and preventing Steve Manske finds that many youth tobacco cancer. Currently, work is being funded in the users choose flavoured products, evidence that following areas: influences several provinces to ban them. • new anti-cancer drugs, including chemotherapy, hormonal therapy, biological Camilla Zimmermann finds that offering palliative therapy and immunotherapy agents care earlier gives patients a better quality of life, • new approaches to cancer prevention, improving experiences for both people living with screening, surgery and radiation therapy cancer and their families. • new combinations of treatments • new ways of using standard treatments 2015: Researchers develop a revolutionary • complementary and alternative cancer cancer-detecting probe that could make a major therapies difference for brain cancer patients.

The Canadian Cancer Society, Heart and Stroke Foundation, Diabetes Canada, Childhood Obesity Foundation and Chronic Disease Prevention Alliance of Canada funded research into the health impacts of sugary drink consumption. This study projects that in the next 25 years, consumption of these beverages will result in: more than 1 million cases of overweight and more than 3 million cases of obesity · almost 1 million cases of type 2 diabetes · almost 300,000 Canadians with ischemic heart disease · more than 100,000 cases of cancer · almost 40,000 strokes Canada has among the highest Crohn’s and Colitis Research incidence rates of Crohn’s and There is no cure for Crohn’s disease or ulcerative colitis. Hence, colitis in the world: research has focused on: 250,000 people living with • developing new drug therapies inflammatory bowel disease • looking at the role of genetics, particularly in people with Crohn’s • understanding how environmental factors may influence the Most commonly diagnosed before development of IBD the age of 30 5,900 children under the age of Research Advances Through the Years: Highlights 10 affected 2003: Crohn’s and Colitis Canada launches IBD Research Institute to coordinate expanded and innovative research initiatives in Canada. 10,200 new cases diagnosed every year 2005: A clinical trial conducted at the Robarts Research Institute shows promising treatment for inflammatory bowel disease.

ANDREA HOPKINS Andrea Hopkins was 21 and a university student when she found out she had a mild form of ulcerative colitis. The inflammatory bowel disease (IBD), which affects the colon, including the rectum and anus, and only invades the inner lining of the bowel tissue, had attacked 10 centimetres of her rectum. Medication worked for a short time, but about a year later, in 2007, shortly after her mother was diagnosed with terminal cancer, Andrea’s mild form became aggressive, attacking her entire large colon within three months. Despite frontline medications, at the age of 25, her colon was removed and she was fitted with an ostomy bag. Thankfully, two years later, she received reversal surgery, which involves using the small intestine to make an internal pouch. Thanks to medical advances into Crohn’s and colitis, Andrea is living a more normal life, without having to rely on an ostomy pouch. Researcher Spotlight Canada’s first bone marrow transplant to John Rioux and a consortium of successfully treat inflammatory bowel disease in other Canadian and American a young girl with a rare genetic mutation of the researchers have identified disease was performed at The Hospital for Sick genetic risk factors associated Children in Toronto in 2017. Only 20 such operations with the development of Crohn’s disease, following have been performed in the world. a search of the entire human genome. These findings will improve the biological understanding of the disease, have a long-term impact on clinical practice, and serve as important targets 2013: Brian Feagan’s clinical trial results show that for the development of drugs that could improve early immunosuppression treatment can alter the therapy — offering new hope for better therapies natural progression of Crohn’s. for patients with Crohn’s disease.

2014: In respective studies, Herota Simon, Current research studies include: André Buret and Wallace MacNaughton study • looking at how immune cells called how PXR keeps the inner lining of the gut tight “macrophages” in Crohn’s disease and ulcerative and protects against the damaging effects of colitis can be altered to decrease inflammation inflammation; how microbiota biofilms cause • testing three new agents now approved for post-infectious flare-ups in IBD; and how PAR2 treatment as an alternative to steroids, with the turns off inflammation. aim to identify and target immune pathways in order to develop personalized therapies and Mark Lathrop discovers new types of high-risk biomarkers for IBD genetic risk factors in IBD. • spearheading the first pediatric fecal transplant study for IBD in Canada and first randomized 2017: Alexio Muise performs Canada’s first bone controlled trial in the world marrow transplant to successfully treat IBD in a young girl with a rare genetic mutation of the disease.

Crohn’s and Colitis Canada, established in 1974, has invested more than $101 million in major research projects. The organization is Canada’s largest non-governmental funder of Crohn’s and colitis research and the second largest in the world. The organization supports research in two streams: advancing discovery and improving life. This research support has helped to position Canada as a global powerhouse for Crohn’s and colitis research. Funding has: • led to new treatments and lower rates of surgery • established Canadian research centres as worldwide centres of excellence • funded the GEM Project, a landmark study to identify the triggers of Crohn’s disease that has grown to 90 study sites around the world 1 in every 3,600 children born in Cystic Fibrosis Research Canada has cystic fibrosis Investing in the best research has led to outstanding progress in the Over 60% of Canadians with CF fight against cystic fibrosis. Canadian researchers have: are over the age of 18 • discovered the gene responsible for cystic fibrosis • developed a revolutionary diet that solved malnutrition in Almost 60% are diagnosed in the cystic fibrosis first year of life and almost 90% • developed a method to repair damaged donor lungs, improving by 12 years of age transplant outcomes • identified a novel approach to treating bacterial infections that was adopted as a best practice in clinical care Note: These 2016 statistics (the latest available) are from the Canadian CF Registry 2016 Annual Data Report.

KAIDEN AMES Sixty years ago, children like Kaiden Ames living with cystic fibrosis didn’t make it to their school-age years. This fatal genetic disease affects the digestive system and lungs. Persistent and ongoing infection in the lungs ultimately destroys these vital organs, and death is inevitable. When Kaiden was born, he had a bowel obstruction. Multiple tests and newborn screening confirmed that he had cystic fibrosis. Thanks to the progress made by cystic fibrosis research over the last few decades, Kaiden is benefiting from the latest drug therapies — “the next best thing to a cure,” says his dad, Jason — and can expect to live well into middle age. Researcher Spotlight Lap-Chee Tsui made what Canadians with cystic fibrosis have is described as the most one of the highest median survival significant breakthrough in rates in the world. human genetics in 50 years — the discovery of the cystic fibrosis gene. An innovator, mentor and role model, he stands as a true giant in the field of human genetics, having made Half of all Canadians with cystic fibrosis born extraordinary contributions to science through today are expected to live into their early 50s and his discoveries. Dr. Tsui is considered a leader in beyond, when most children did not live long developing the field of genomics in Canada and enough to attend kindergarten in the 1960s. internationally, and his contributions offer new hope for diagnosis and treatment to countless Research Advances Through the Years: Highlights people afflicted with cystic fibrosis. Dr. Tsui is a 1974: Revolutionary new diet for people living member of the Canadian Medical Hall of Fame. with cystic fibrosis is adopted into standard practice worldwide. Current research studies include: • examining the protein that is defective in cystic 1988: The world’s first successful double-lung fibrosis with an aim to improve its function transplant on a person with cystic fibrosis takes • growing and studying bacterial interactions in place in Toronto. the lab, enabling researchers to find out more about how to fight them in the human body 1989: SickKids researchers Lap-Chee Tsui, Manuel • reducing the effects of tissue-damaging Buchwald and Jack Riordan, together with Francis inflammation Collins from the University of Michigan, discover • accelerating the discovery of new treatments the gene that causes cystic fibrosis. and determining the most effective, personalized therapies in partnership with the 1992: Researchers establish a new therapeutic SickKids Foundation in Toronto approach to treat bacterial infections by using alternating courses of different antibiotics.

2005: Researchers identify the modifier gene that affects the severity of cystic fibrosis in different individuals.

2009: In preclinical studies, gene therapy is shown to repair injured donor lungs prior to transplantation.

Established in 1960, Cystic Fibrosis Canada is one of the world’s top three charitable organizations committed to finding a cure for cystic fibrosis. As an internationally recognized leader in funding innovation and clinical care, the organization invests more in life-saving cystic fibrosis research and care than any other non- governmental agency in Canada. The investment of more than $244 million in leading research, innovation and care has contributed to dramatic improvements in the survival rates of Canadians with the disease. 1 in 3 Canadians has diabetes Diabetes Research or prediabetes Young Leonard Thompson, a “charity patient” at the Toronto General Every 3 minutes, another Hospital, became the first person to receive an injection of insulin to Canadian is diagnosed treat diabetes, thanks to the discovery of insulin by Dr. Charles Best and Dr. Frederick Banting in 1921. Diabetes rates are 3 to 5 times higher in First Nations people Since then, the scope of diabetes research in Canada has been vast and the numerous studies both varied and unique. Huge strides and key advances have been made in mapping and understanding the physiology, biochemistry and genetics of diabetes.

DWAYNE VERMETTE Dwayne “Bubba” Vermette sank into a deep depression and gained a lot of weight after being diagnosed with type 2 diabetes in his 30s. When Dwayne was first diagnosed, he realized he had to make some critical lifestyle changes if he wanted to live a long life. Thanks to medications to manage his disease — he takes two oral diabetes medications every day instead of the insulin he was having to rely on — and with the help of family and health care professionals, Dwayne exercises daily and lost 107 pounds. Today, he’s healthier than he’s ever been. Research Advances Through the Years: Highlights Canada has been a leader in diabetes 1921: Frederick Banting, Charles Best and research since the discovery of insulin collaborators James Collip and J.J.R. Macleod discover insulin, which revolutionized the in 1921. treatment of diabetes and gave the Canadian scientific community its first Nobel Prize.

1922: Peter Joseph Moloney develops a method Researcher Spotlight to concentrate and purify insulin, allowing for Daniel Drucker, a long-time large-scale production. Canadian Diabetes Association- funded researcher and a senior 1989: The islet transplant group, established by investigator at Mount Sinai Ray Rajotte, in Alberta, performs Canada’s first Hospital’s Lunenfeld-Tanenbaum islet transplant. Research Institute, focuses on hormones made in the pancreas, digestive tract and brain, and 1999: Ray Rajotte and James Shapiro transplant how they control food intake and the disposal human donor pancreatic islet cells into patients of nutrients. His discoveries have led to the with chronic type 1 diabetes. development of two new groups of drugs to treat type 2 diabetes. Winner of CDA’s Young 2000: Jacques Drouin identifies a gene mutation Scientist Award in 1996, Dr. Drucker has also been responsible for severe hypoglycemia in infants. recognized by the American Diabetes Association and was awarded the 2014 Manpei Suzuki 2003: Mickie Bhatia uses stem cells to trigger the International Prize for Diabetes Research for his growth of insulin-producing cells in the pancreas, extensive and ground-breaking contributions over effectively curing diabetes in mice. the years to many landmark discoveries.

2006: Hertzel Gerstein and Salim Yusuf find that Current research studies include: rosiglitazone reduces the risk of developing type 2 • studying the effectiveness of viscous dietary diabetes by 60%. fibre, whole grain and ginseng therapies in reducing the risk of type 2 diabetes 2007: Rob Sladek and his team identify mutations • evaluating the role of vitamin D in preventing on the genes that are associated with increased and treating diseases associated with risk of type 2 diabetes. insulin resistance • using peer support as a transition model 2008: Tony Lam discovers a new signaling for improving long-term diabetes-related pathway between the gut, the brain and the liver health outcomes that lowers blood sugar, creating the possibility of new treatments for people with diabetes.

Diabetes Canada (previously known as the Canadian Diabetes Association, which was formed in 1953) is active in more than 150 Canadian communities and supports people living with diabetes through research, advocacy, education and services. Since 1975, it has funded more than $135 million in diabetes research. Annual research grants — totaling $5 million — support research in four key areas: basic biomedical, clinical, health services, and population and public health. 600,000 Canadians live with Heart Disease and Stroke Research heart failure Seventy-five years ago, about 35% of people who made it to a 50,000 people are diagnosed hospital after a heart attack did not survive. Thanks to tremendous with heart failure every year strides in research advances, today that number is down to 5%. In fact, the death rate from heart disease and stroke combined has Heart disease and stroke take declined more than 75% over the past 60 years. The success rate 1 Canadian life every 7 minutes for infants born with complex heart defects is equally startling: 90% 9 in 10 Canadians have at least survival rate today compared to 20% six decades ago. one risk factor, such as high blood pressure, obesity, tobacco use, lack Much of this success is directly related to research advances in of physical activity and diabetes prevention, diagnosis, treatment and care, including: • identifying, treating and managing risk factors such as high blood pressure and cholesterol • cutting smoking rates by much more than half • understanding the physical causes of heart disease • discovering new procedures, such as angioplasty

JACKSON BROGAN It took time for the medical team to diagnose what was wrong with Lisa and Ryan Brogan’s son, Jackson, whose eyes were pulling off to the left. After ruling out a range of possibilities, they made the shocking discovery that little Jackson, at the age of 15 weeks, had suffered a stroke. It’s been over five years since that diagnosis, and Jackson is doing well — in no small measure due to the rehabilitation treatment he received at the Janeway Children’s Health and Rehabilitation Centre in St. John’s, Newfoundland. The decades of research advances into pediatric stroke as a result of funding by Heart and Stroke made Jackson’s recovery possible. Canada is renowned for cutting-edge heart research, 2003: The Canadian Stroke Strategy revolutionizes such as aortic valve replacement, use of stem cell stroke management.

transplantation to repair muscles damaged during 2009: The world’s first in-utero surgery to correct heart attacks and robotics-assisted heart surgery. congenital heart defects is performed in Canada.

2013: Researchers bioengineer the first-ever Research Advances Through the Years: Highlights living, three-dimensional human arrhythmic 1921: Frank Schofield identifies a potent heart tissue. anticoagulant that leads the way to the discovery of vitamin K inhibitors, which prevent strokes and 2015: The ESCAPE trial, which transforms stroke heart attacks caused by blood clots. treatment by treating major strokes by removing blood clots through blood vessels, cuts deaths by 1951: John Alexander Hopps develops the world’s 50% and significantly reduces disability. first external cardiac pacemaker. Researcher Spotlight 1954: Wilfred Bigelow performs the first Wilfred Bigelow’s key discovery, in 1950, was successful open-heart surgery in Canada. recognizing how to lower the body’s oxygen requirements while lowering its core temperature 1968: One of the first heart transplant surgeries in to a point at which safe open heart surgery was Canada is performed. possible. The first successful human application of his hypothermia research for open heart surgery 1972: Jack Hirsh observes heparin’s anti- took place in 1953. Meanwhile, another major coagulant ability to treat blood clots in veins, advance in the management of heart disease a finding that has immediate and widespread which he pioneered — the pacemaker — evolved clinical applications. quite unexpectedly out of his hypothermia research. Together, these discoveries revolutionized 1976: Henry Barnett demonstrates that heart surgery and have made a significant acetylsalicylic acid (aspirin) can prevent strokes. difference to the lives of millions of people with heart disease. He is a laureate in the Canadian 1980: Adolfo de Bold discovers the hormone that Medical Hall of Fame. controls high blood pressure. Current research studies include: 1989: Wilbert Keon becomes the first • testing a new tissue engineering technique to Canadian heart surgeon to perform a neo-natal replace damaged tissues after a heart attack heart transplant. • testing the safety of a drug that turns certain genes on to improve heart function after a 1999: Douglas Boyd performs the first robotics- heart attack assisted closed-chest bypass surgery. • focusing on covert strokes — small strokes in the brain that cause subtle symptoms — 2000: ACE inhibitors are found to significantly now considered to be quite common reduce the risk of heart attacks and strokes. among Canadians

For more than 60 years, Heart & Stroke has been dedicated to fighting heart disease and stroke — to date, investing $1.45 billion into life-saving research. This research has led to breakthroughs such as heart transplant surgery and a revolutionary stroke treatment that cuts the death rate by 50%. 1 in 7,000 Canadians has Huntington’s Disease Research Huntington’s In 1841, medical student Charles Oscar Waters described a condition 1 in every 5,500 is at risk called “magrums,” which medical historians now believe is our first of developing the disease description of Huntington’s disease. However, a genetic test wasn’t available until after the discovery was made in 1976 that the HD gene was on the tip of chromosome 4. And, in 2011, researchers discovered a common link between Alzheimer’s and Huntington’s.

Research into this genetic disease — for which there is still no cure — is slow. It will be through clinical trials that new research breakthroughs will be moved from discovery to the HD community. For a clinical trial to be successful, a wide participation rate is required in order to find meaningful results. The Huntington

HANK PATTERSON Those who carry the Huntington’s disease gene have a 50% chance of passing it on to their child. Hank Patterson’s mom suffered from the disease and Hank found out he had the gene soon after marrying his wife. When Sharanie became pregnant, they had their baby tested in vitro — who, thankfully, is not a carrier. It was the happiest day of Hank’s life. Huntington’s is a terrible disease that progressively impairs the ability of people to control their movements. “It strips people of who they are, from their own personality and their ability to communicate with others,” says Hank, who remains hopeful that in 10 or 15 years, researchers will find a way to delay the onset of the disease, stop it from progressing — maybe even find a cure. Society of Canada plays a key role in bridging the Canadians are becoming the highest relationship between researchers and individuals per capita participants in HD clinical by educating Canadians on the importance of the trials in the world. clinical trial process; how they can get involved; and why their participation is so crucial. For example, in 2015, five clinical trials were launched to address the root cause of Huntington’s disease. Researchers at the University of British Columbia Research Advances Through the Years: Highlights help identify a gene variant that influences 1984: Michael Hayden establishes a predictive whether Huntington’s breaks out earlier or later testing centre in Vancouver — 1 of only 3 in than expected. the world. Researcher Spotlight 1986: Michael Hayden develops a genetic test for One of the greatest hopes Huntington’s disease, the first ever predictive test for effective treatment of for any genetic disorder. Huntington’s disease is the work of Michael Hayden. His work 1993: Jim Gusella and his team discover the HD has profoundly advanced our gene mutation. Direct testing becomes available, understanding with respect to the genetic basis of providing those at-risk with a definitive answer as Huntington’s, and research into the mechanisms to whether they will develop Huntington’s. of the disease have produced reliable predictive tests — offering new opportunities for prevention 2006: Michael Hayden stops the progression of and treatment. Dr. Hayden is a member of the the disease in a mouse. Order of Canada and the Canadian Medical Hall of Fame. 2012: Simonetta Sipione in collaboration with Ray Truant successfully reverses the motor Current research studies include: symptoms of Huntington’s in a mouse. • developing new ways to measure huntingtin, the protein responsible for neuron loss 2013: Ray Truant solves a long-standing • testing a new gene silencing drug designed to mystery in fighting the disease — the ability halt production of a toxic protein that causes to examine how cells change shape in human brain wasting Huntington’s patients. • developing therapeutics

2015: Blair Leavitt begins a clinical trial to test a new drug to treat Huntington’s.

The Huntington Society of Canada, founded in 1973, funds research projects to reverse, slow or prevent the progression of Huntington’s. Since its founding, the Society has invested over $30 million into research and services. A key funding channel is the Navigator Program, launched in 1998, where funding is made available to scientists across Canada. The Society’s research council reviews and awards research grants, as well as offers advice about research projects and proposals that may be funded in concert with other national and international funding bodies. To expedite the discovery of treatments to slow and prevent Huntington’s, the Society entered into a $2-million joint partnership with Brain Canada in 2016. Research investment has also been made into “gene-silencing,” a huntingtin-lowering therapy that targets the disease at its root. In addition, 4 sites in Canada are participating in the PREDICT-HD study, a multi-centre observational research study involving 32 international sites. 2,500 Canadians are affected by Inherited Bleeding Disorder Research hemophilia A Hemophilia can be traced back to the 10th century, but advances in 600 Canadians are affected by treatment and care did not begin until the mid-20th century. During hemophilia B the 1950s, effective hemophilia therapy began in a few of the most advanced centres, but the single biggest breakthrough in care came 30,000 to 35,000 Canadians have in the 1960s with the discovery of cryoprecipitate. The provision of von Willebrand disease concentrates in the 1970s led to home care and the development 1 in 100 Canadians carry an of the concept of comprehensive care centres. Spurred on by the inherited bleeding disorder gene tragedy of HIV and the isolation of the hepatitis C virus in the 1980s, many advances in blood safety were realized, including the first clinical trials with human recombinant FVIII and Canada becoming the first country in the world to switch entirely to this recombinant in 1993.

Today, different gene therapies are being tested, and current treatments, such as extended half-life (EHL) factor concentrates, continue to be improved through research on modified clotting factor proteins.

Research Advances Through the Years: Highlights 1975: Raymond Lemieux synthesizes the sugar molecule found on the surface of type B blood cells, leading to improved treatments for hemophilia and leukemia, as well as new antibiotics and anti- rejection drugs.

2015: Health Canada approves first long-acting products.

CALEN VAN DE VEEN Calen was diagnosed with hemophilia at the age of 9. He could no longer take part in sports and other physical activities due to risk of injury and joint bleeds. Four years later, at the age of 13, he started prophylactic treatments at the Saskatchewan Bleeding Disorders Clinic, a partner of the Saskatchewan chapter of the Canadian Hemophilia Society. The treatments were a life- changer: he learned how to self- infuse — critical for people who live far away from a hemophilia treatment centre. Calen also learned how to watch for signs that meant he needed treatment. The Canadian Hemophilia Society helped reform and important work. She has received the U.S. Canada’s blood system following the contamination National Hemophilia Foundation Researcher of of Canada’s blood supply in the 1970s and 1980s, the Year Award, the Queen’s University Health Sciences Faculty Basmajian Research Award and the infection of transfusion recipients with the and the Canadian Hemophilia Society’s Dr. Cecil hepatitis C virus. Harris Award.

Research studies in 2017 include: • studying the von Willebrand factor in 2016: Antihemophilic Factor (Recombinant) megakaryocytes and the role of platelet-VWF in is approved for use in children and adults with von Willebrand disease hemophilia A in Canada — the first country to • investigating possible causes for the increased receive approval. risk of factor VIII inhibitor development • understanding how the Gfi1b gene functions 2017: St. Michael’s Hospital in Toronto participates and regulates platelet formation to gain new in promising gene therapy clinical trial, using insight on how to treat patients with bleeding a gene engineered to replace the faulty one in disorders and platelet deficiencies people with hemophilia. The engineered gene is • developing an evidence-based training placed into an inactivated virus and then infused program for mentors for a virtual peer-to-peer into the liver, where it helps the body produce a hemophilia mentoring program for teens clotting factor that prevents bleeding. • helping doctors, nurses and other health care professionals who are involved in the care of Researcher Spotlight babies with bleeding disorders develop more Dr. Paula James is considered an international star effective and standardized ways of giving in the inherited bleeding disorders community. this care Regularly asked to provide advice about the • identifying the most important and feasible management of patients with von Willebrand clinical and patient-reported outcome disease from all over Canada, she will be invited indicators of effective transition to be a senior author for the next international • determining whether desmopressin clinical guidelines document being developed (DDAVP) versus exercise in patients with with the support of the World Federation of mild hemophilia A is better and if they work Hemophilia, American Society of Hematology, synergistically in improving hemostasis and International Society on Thrombosis and • understanding the role of point-of-care joint Haemostasis. Dr. James leads a successful ultrasonography in managing hemophilia research program that has produced novel

Supporting research towards improving the health and the quality of life of all people with inherited bleeding disorders and finding a cure have been goals of the Canadian Hemophilia Society since it was founded in 1953. The Society has helped build a network of hemophilia treatment centres across Canada to provide comprehensive care and treatment. Every year, it invests about $500,000 in research projects to improve treatment and find a cure. Through the Dream of a Cure research program, the Society has funded more than 60 research projects, supported 50 Canadian researchers and invested close to $3 million. Grants are awarded for basic scientific research grants and studentships, clinical research in fields relevant to improving the quality of life for persons with hemophilia or other inherited bleeding disorders, persons with related conditions such as HIV or hepatitis C, and those who are carriers of an inherited bleeding disorder. The CHS also allows Canadian investigators to conduct research on psychosocial aspects of bleeding disorders, including outcome evaluation. 1 in 10 Canadians has kidney disease Kidney Disease Research 36,251 Canadians are being treated for In the 1960s, people with kidney failure had little hope of survival. kidney failure Dialysis was considered an extraordinary treatment and restricted to very few. Transplantation was still experimental. Number of Canadians living with end-stage kidney disease has grown 36% since 2006 47% of new patients are under the age of 65 46.5% of kidney transplants are from living donors 58.5% Canadians with kidney disease are on dialysis 41.5% have a functioning transplant

MARIE-EVE CHAINEY Marie-Eve Chainey was an elite high jumper. On top of the sports world, she left her home town of Kapuskasing to train in Spain on an exchange program when she was just 18. But shortly after arriving in Spain, she started to gain weight, was bruising easily and became dizzy. Her kidneys had shut down. Marie-Eve returned home to Canada. Over the next two years, she needed more than 800 transfusions and regular dialysis treatments. Once she became medically stable, she decided to go back to school, entering the nursing program at the University of Ottawa. After four relapses, Marie-Eve learned she had atypical Hemolytic Uremic Syndrome. A kidney transplant was ruled out at the time, but thanks to a miracle drug called Soliris her health stabilized. Fast track ahead, after competing for the last time at the age of 34, Marie-Eve said goodbye to high jumping and entered The Ottawa Hospital to receive a much-needed kidney. Her aunt was the donor. After 20 trying and difficult years, Marie-Eve has her life back. Kidney disease research over the last 50 years has: • led to the development and perfection of dialysis treatment Some of the finest kidney disease • made transplantation the treatment of choice researchers in the world are in Canada. for an increasing number of people • led to the development of anti-rejection drugs

Research Advances Through the Years: Highlights 1958: John Dossetor coordinates a successful kidney transplant between identical twins at the Royal Victoria Hospital in Montreal, the first kidney proved to be an effective anti-rejection drug for transplant in the Commonwealth. kidney transplants, as well as for heart, intestine, lung and bone marrow transplants. Dr. Stiller is 1970: Calvin Stiller confirms the effectiveness of a member of the Canadian Medical Hall of Fame the drug cyclosporine for kidney transplants. and is an Officer of the Order of Canada.

Researcher Spotlight Current research studies include: Calvin Stiller was Canada’s major • conducting the world’s first gene therapy voice in organ transplantation clinical trial for Fabry disease, which involves during the 1970s, 1980s and removing stem cells from a patient’s blood, early 1990s when the field inserting a working copy of a new gene into the transformed from a risky stem cells using a specially engineered virus, experimental undertaking and then transplanting the stem cells back into into a reliable, successful venture. In 1970, he the donor patient obtained the promising new drug cyclosporine • understanding the role of the Sox4 and Sox11 and organized its first multi-centre clinical trial in genes in kidney development kidney transplantation in North America, studying • moving stem cells to an “off-the-shelf” the effectiveness of the immunosuppressive drug treatment for kidney disease cyclosporin for kidney transplants. Cyclosporin

The Kidney Foundation of Canada, which was established in 1964, is a leading funder for kidney-related research that has made kidney transplants so successful. These advances and countless others were made possible thanks to the thousands of hours and millions of dollars first being spent on basic and clinical medical research. The Foundation’s National Research Program has grown to become one of the most important sources of funding for scientists conducting kidney-related research. 1 in 4 Canadians — 7 million — Liver Disease Research may have liver disease There has been a nearly 30% increase in liver-related deaths over Liver cancer is one of the fastest- an eight-year period. In addition to this, a dramatic increase in the rising and deadliest forms of incidence of cirrhosis and liver cancer was also observed. Until 2013, cancers in Canada when the Canadian Liver Foundation released these and other findings in its landmark report Liver Disease in Canada: A Crisis in the 30% increase in deaths from liver Making, little was known about liver disease. disease over eight years, with cases most prevalent in Alberta, B.C., Ontario and Quebec

ANNETTE MARTIN Just 30 years ago, many children born with biliary atresia, a rare disease of the liver and bile ducts that occurs in infants, did not survive. Annette’s son Craig was one of them. When he was born, he had issues with his liver; two months later, he was diagnosed with the rare liver disease that affects one in every 10,000 to 20,000 infants soon after birth. Surgery was performed to try to unblock the bile ducts, but his only chance of survival was a liver transplant, which at the time was not an option in Canada. At 9 months old, Craig was flown to Pittsburgh for the operation. He passed away 10 days later. If Craig had been born today, he would have been able to receive a transplant in Canada — and he probably would have survived. That’s because, today, thanks to medical advances in liver transplantation, the survival rate is 90%. To help advance research, in 2014, the Foundation helped launch, and has committed $500,000 to, the Canadian National Transplant Research Liver disease is a growing health Program. The program, involving research teams crisis — in Canada and globally. from 18 transplant centres and 15 universities and research centres worldwide, is focused on improving outcomes for transplant patients and finding ways to increase the availability of organs. decreased replication of HBV. This was the first Research Advances Through the Years: Highlights antiviral drug used to treat HBV, and allowed liver 2010: Diana Mager looks at ways to counteract transplantation programs for hepatitis B carriers to protein energy malnutrition in infants by boosting be reinstated. Turning to hepatitis C, Dr. Tyrrell and the amino acids that babies with biliary atresia two colleagues developed an immune-deficient receive prior to liver transplants. mouse with a humanized liver, making it possible to test hundreds of compounds as potential drugs 2014: Gregory Steinberg studies how metformin, against hepatitis C. Dr. Tyrrell is a member of the a diabetes medication, reduces the risk of Canadian Medical Hall of Fame. developing liver cancer. Current research studies include: 2015: Binita Kamath uses stem cells to replicate • understanding how nanoparticles target and an infant’s liver disease to test treatments. destroy immune cells that help liver cancer evade detection and grow Researcher Spotlight • studying how obesity re-wires the liver to over- Lorne Tyrrell’s work has produce cholesterol positioned Canada as a world • re-educating the immune system so it will leader in the field of hepatitis accept a newly transplanted organ rather research. His ground-breaking attacking it like a foreign invader research, using duck liver cells • testing a machine called the “OrganOx metra®” as an alternate model system to determine how well damaged livers function, to test hepatitis B virus inhibitors, led to the and whether they can be repaired and used discovery that Lamivudine (3TC) dramatically in transplantation

Formed in 1969, the Canadian Liver Foundation invests in life-saving research, supports new advances and breakthroughs, and helps improve the lives of Canadians living with liver disease. Through its research grants program, the Foundation has supported the work of Canada’s leading researchers and scientists — and has played an important role in several important scientific breakthroughs. These include the discovery of genes responsible for Wilson’s disease and hemochromatosis, as well as various new treatments for hepatitis C and other forms of liver disease. Lung Disease Research 1 in 5 Canadians has lung disease While Canada has come a long way in understanding and treating lung disease, breathing challenges continue to exact an enormous 13% of Canadian children have asthma human and economic toll. One in five Canadians has trouble Lung cancer claims more lives than breast, breathing; it’s a constant struggle that affects almost every aspect of ovarian and prostate combined their daily lives.

Asthma and COPD together affect almost Inside hospitals and in university labs, some of the country’s most 15% of Canadians inquiring minds are engaged in pursuing the answers that will COPD is the leading cause of hospitalization unlock the secrets of better breathing. Examples of the types of questions researchers are asking include: Are there “good bacteria” in mother’s breast milk that could prevent asthma? Why is a certain ethnic group susceptible to a certain disease? Could a molecule be the missing link?

DOUG COOPER Over 30 years ago, Doug Cooper began to have trouble breathing. He found himself out of breath, even when trying to take the stairs two at a time. When he found himself eventually gagging and gasping for air after going up a mere three steps, he knew it wasn’t a case of getting older. Initially, the thought was that Doug had asthma, but this was ruled out when his breathing problems continued despite trying different asthma medications. Subsequent tests confirmed that Doug had chronic obstructive pulmonary disease, a lung disease that includes chronic bronchitis and emphysema. COPD damages the breathing tubes that carry air in and out of the lungs, as well as the tiny air sacs at the tips of the airways. Doug realized that COPD was not a little thing: there isn’t a cure and it can kill a person if they don’t take the necessary steps to deal with the disease. With the help of the Lung Association, Doug joined a regular exercise class geared to people with COPD and took medication. Once he began to improve, he was able to get off the steroids. 2009: Amy Plint discovers that a combined Launched in February 2014, the Canadian Respiratory therapy of dexamethasone and epinephrine significantly reduces hospital admissions for Research Network is a national research network that infants with bronchiolitis. brings together researchers from across Canada to work together to improve understanding and treatment of 2014: Paul O’Byrne and Gail Gauvreau successfully asthma and COPD, which together affect almost 15% test an antibody that may lead to an improvement of Canadians. The Association is investing $1.08 million in the quality of life for asthma patients by reducing inflammation in the lungs. towards the Network over a five-year-period. Researcher Spotlight One of Canada’s greatest pulmonary physicians, clinician-scientists and original thinkers, Peter Macklem forever changed the face of respiratory medicine by pioneering the study of small airway Research Advances Through the Years: Highlights physiology and identifying the early pulmonary 1914: The field of thoracic surgery is developed. damage caused by smoking. He is recognized worldwide as a giant of respiratory medicine. 1940: An early diagnosis of tuberculosis is made Dr. Macklem also helped to pioneer the concept through chest x-rays. of respiratory muscle fatigue, which had a direct impact on the management of patients in the Pulmonary damage caused by smoking is identified. intensive care unit and helped lead to a better understanding of the role of the respiratory 1970: The first successful trials of the anti- muscles in pulmonary disease. He is a member of rejection drug cyclosporine is used in the Canadian Medical Hall of Fame. lung transplants. Current research studies include: 1983: Joel Cooper performs the first successful • using new micro X-ray imaging to detect how lung transplant in the world. airways get damaged by smoking • studying how air pollutants damage lung cells 2003: Researchers at the Michael Smith Genome • looking for the causes of shortness of breath Sciences Centre crack the genetic sequence of the during exercise in people with mild COPD virus believed to cause severe acute respiratory • finding new therapeutic treatments for asthma syndrome (SARS). patients when their airways become inflamed by an asthma trigger, such as moulds, pollen 2007: Marcelo Cypel, Dirk Van Raemdonck and and dust Shaf Keshavjee introduce the first concept of prolonged Ex-vivo lung perfusion.

For over 100 years, the Canadian Lung Association has been dedicated to promoting and improving lung health for all Canadians. To achieve its mission to lead nationwide and international lung health initiatives, prevent lung disease, help people manage lung disease and promote lung health, the Association supports critical world-class, high-impact research and funds everything from basic lab research to clinical trials to studies in lung disease prevention. Between 2012 and 2016, it funded 300 projects for a total investment of $11.8 million. Canada has the highest rate of Multiple Sclerosis Research multiple sclerosis in the world First recognized as a distinct disease in 1868 by the French 100,000 Canadians live with MS neurologist Jean-Martin Charcot, multiple sclerosis (MS) continues to baffle scientists and the medical community. It’s the most common Canadian women are 3 times autoimmune disorder affecting the central nervous system. more likely to develop MS than men Although we still don’t know what causes MS or how to cure it, researchers are coming ever closer to finding answers. Thanks to painstaking immunological research, we know so much more about the role of the immune system in MS than we did even 15 years ago.

JENNIFER MOLSON Jennifer Molson was diagnosed with multiple sclerosis at age 21. After years of struggling with the effects of the disease, she had an opportunity to take part in a clinical trial that was funded by the Society’s affiliate, the Multiple Sclerosis Scientific Research Foundation. The Canadian bone marrow transplantation trial was a success — and gave Jennifer a second chance at life. But it wasn’t easy. For three years, between 2002 and 2005, Jennifer’s body didn’t feel like her own. At one point she was taking 129 pills a day and her stomach lining was so eroded that she couldn’t keep food down for a year. Although Jennifer is very prone to infection — she developed a blood infection, shingles and bladder infections after the treatment — she did regain the ability to walk, ski, kayak, even dance at her own wedding. She also returned to work full-time. 2017: Luanne Metz shows that minocycline, a The findings from the Canadian Bone Marrow safe, common antibiotic used to treat common Transplantation trial — the only one of its acne, has important benefits in treating and kind in Canada — represent an important delaying the progression of early-onset MS. breakthrough in research exploring cell-based therapies for aggressive forms of relapsing- University of Alberta researchers, working with an international team, discover an underlying defect remitting MS. in brain cells that may cause MS.

Jacqueline Quandt’s study on mice indicates that a simple compound slows down the progression of MS. Research Advances Through the Years: Highlights 2007: Alexandre Prat uncovers a mechanism used Researcher Spotlight by white blood cells to attack the brain and the Thomas Murray’s greatest spinal cord in people with MS. legacy is in the field of multiple sclerosis. In addition to founding 2010: Allison Kraus discovers that a misfiring and directing the Dalhousie gene called calnexin appears to contribute to Multiple Sclerosis Research unit MS and a related disorder called “Charcot-Marie- for over 20 years, he founded the International Tooth disease”. Consortium of Multiple Sclerosis Centres and has contributed to the research and education of this 2013: Researchers challenge controversial theory disease nationally and internationally. Dr. Murray is of cause of MS, transforming diagnosis and care. a member of the Canadian Medical Hall of Fame. The B.C. study finds that narrowing of the veins from the brain to the heart is just as prevalent in Current research studies include: people without the disease. • establishing an imaging biomarker for disease progression 2016: Scientists in British Columbia find a genetic • evaluating the use of disease-modifying link to MS, marking a breakthrough that could one therapies in pediatric MS day allow doctors to identify and treat the disease • understanding the causes and consequences of before symptoms surface. pediatric MS

Founded in 1948, the MS Society of Canada has provided over $150 million towards MS research that furthers our understanding of the disease, seeking new treatments and a cure. In 2016 alone, it invested $10 million in research through grants, scholarships, fellowships and investments through the Multiple Sclerosis Scientific Research Foundation. It also funded $8 million in programs and services, including financial support for daily living or equipment need. The Society established the Multiple Sclerosis Scientific Research Foundation in 1973 with an investment of $1,000. Today, the Foundation is the largest fund in the world dedicated strictly to MS research. It supports innovative and transformative research beyond the scope of the MS Society’s regular granting program. In particular, the focus is on interdisciplinary research that fosters multi-site collaboration and accelerates fundamental advances in understanding and treating MS. Examples of such research are the Foundation’s recently announced stem cell trial, research into progressive MS, and the ongoing investigation of pediatric MS. More than 50,000 Canadians are affected by Muscular Dystrophy Research neuromuscular disorders Muscular dystrophy (MD) and many related neuromuscular disorders are genetic diseases caused by errors in genes associated There are more than 150 different types of with muscle function. First described in the 1830s by Charles Bell, neuromuscular disorders the disease is caused by incorrect or missing genetic information Roughly 800 Canadian children between the that prevents the body from making the proteins needed to build ages of 0 and 24 are diagnosed with Duchenne and maintain healthy muscles. In some cases, MD starts causing muscular dystrophy muscle problems in infancy; in others, symptoms don’t appear until adulthood.

JEAN-PIERRE BÉLAND Jean-Pierre Béland was only 30 years old when he started to have difficulty walking; 31 when he had to quit working. The year was 1985. At the time, doctors couldn’t pinpoint what he had — only that it was a muscle-related illness — and it took eight more years before the diagnosis came from specialists at the Montreal Neurological Institute and Hospital. Jean-Pierre had mitochondrial myopathy, a disease that falls under the muscular dystrophy family. The disease affects the mitochondria, tiny energy-producing structures that are a cell’s “power plants.” A defect — which in Jean- Pierre’s case was inherited through his mother’s side — in either a mitochondrial gene or a gene in the cell nucleus affects the ability of the mitochondria to function. In the 33 years that Jean-Pierre has lived with mitochondrial myopathy, he has had one health scare — when the doctors found an aneurysm in his abdomen and had to operate. It could have been a life-or-death situation. To improve his respiratory health, Jean-Pierre gave up smoking and practises a healthy lifestyle, thankful that his symptoms haven’t deteriorated significantly. Although his muscles have weakened, he can still negotiate stairs and operate a motor vehicle; he also uses a motorized scooter, which he acquired through Muscular Dystrophy Canada’s equipment program. Between 2000 and 2012, a partnership with the Researcher Spotlight ALS Society of Canada and CIHR saw an investment A ground-breaking study out of the University of Ottawa was of more than $43 million into 177 Canadian basic, the first to demonstrate that focused or applied neuromuscular research grants. Duchenne muscular dystrophy directly affects muscle stem cells. Originally, it was thought that the muscle While there is no cure, researchers are learning weakness is primarily due to problems in muscle more about how to treat it. Physical therapy, fibres, but research conducted by Michael braces, corrective surgery and assisted ventilation Rudnicki shows that it is also due to intrinsic can help manage symptoms. Medications defects in the function of their muscle stem cells. include steroids to slow muscle degeneration, This finding, which completely changes our anticonvulsants to control seizures and some understanding of Duchenne muscular dystrophy, muscle activity, and immuno-suppressants to could eventually lead to far more effective delay damage to dying muscle cells. treatments. Dr. Rudnicki is the director of the regenerative medicine program at The Ottawa Research Advances Through the Years: Highlights Hospital and holds the Canada Research Chair in 2010: Jacques Tremblay and his team design Molecular Genetics. enzymes with the ability to correct the dystrophin protein — making it possible to one day correct Current research studies, among the 2017–18 seed the dystrophin protein that causes Duchenne grant recipients, include: muscular dystrophy. • using state-of-the-art technology to analyze the molecular mechanisms involved in muscle 2015: Michael Rudnicki and his team show for membrane repair the first time that Duchenne muscular dystrophy • validating home portable monitors for directly affects muscle stem cells — a finding diagnosing sleep-disordered breathing in teens that not only changes the medical and scientific and adults with neuromuscular disorders world’s understanding of the disease but could • promoting healthy weights to support eventually lead to more effective treatment. respiratory function in children with Duchenne muscular dystrophy Researchers at The Hospital for Sick Children use the gene editing tool CRISPR to remove a duplicated gene from a genome.

Neuromuscular research was a driving reason for the formation of Muscular Dystrophy Canada in 1954. At that time, little research was being done in Canada or elsewhere in the world. Since then, over $64 million has been put towards research. Research through the Rachel Fund for Myotonic Dystrophy supports genetic and cellular research into myotonic dystrophy ($1.5 million since 2005) while respiratory care grants support research to help improve respiratory care for people living with neuromuscular disorders. The goal is to: • uncover new treatments and therapies • help people with neuromuscular disorders live longer and healthier lives Partnerships with other organizations and individuals also help Muscular Dystrophy Canada leverage higher investments in research. For example, it invested $700,000 to support collaborative research projects on several neuromuscular disorders through the Canadian Institutes of Health Research (CIHR). Second most common Parkinson’s Disease Research neurodegenerative disorder after It’s been 200 years since Dr. James Parkinson of England first Alzheimer’s disease described the brain disease named after him. Since 1817, major 100,000+ Canadians have advances have been made in Parkinson’s research, including the Parkinson’s development of various drug and other therapies to treat disease symptoms. And yet we still do not know precisely what causes 25 new diagnoses every day Parkinson’s disease, and there is no cure. Average age of diagnosis is 60 years

HERB DURAND Herb Durand, once a police officer, has lived with Parkinson’s for over 15 years. Faced with years of degeneration and almost constant shaking — the disease had robbed him of the ability to walk, sit down unaided or even feed himself — he decided to try deep brain stimulation (DBS) surgery. A device is implanted that sends electrical signals to brain areas responsible for body movement. Electrodes are placed deep in the brain and are connected to a stimulator device in the chest. Similar to a heart pacemaker, the stimulator uses electric pulses to regulate brain activity. During three visits to Toronto, Herb underwent stringent tests to measure his personality and suitability to undergo the surgery, which took place in late 2014. The results have changed his life. Herb feels he’s regained 10 years of lost life — and he can hold his grandchild without shaking. For Herb and his wife, Anna, research into Parkinson’s made it possible to develop and improve DBS surgery — and significantly improve the lives of those who have Parkinson’s and their families. Research Advances Through the Years: Highlights Parkinson Canada is the largest, non- 2001: Ivar Mendez transplants brain cells from government funder of Parkinson’s fetal tissue into the brains of 10 Parkinson’s research in Canada. patients who hadn’t responded to other therapies.

2007: Frederic Calon and Francesca Cicchetti discover that omega-3 fatty acids protect the Researcher Spotlight brain against Parkinson’s. Edward Fon is a neurologist and scientist at the Montreal Neurological Institute and Hospital, 2012: Matthew Farrer leads international team associate professor at McGill University, and that identifies the latest gene associated with director of the McGill Parkinson Program, typical late-onset Lewy body Parkinson’s. a national Parkinson foundation centre of excellence. He is particularly interested in the 2013: Edward Fon and Kalle Gehring discover the function and cell biology of Parkinson’s disease three-dimensional structure of the protein Parkin, genes — work that could potentially lead to a discovery that could lead to new drugs to slow innovative new therapeutic strategies. Chair of the progression of Parkinson’s. the Scientific Advisory Board, Parkinson Society Canada, Dr. Fon has received several awards for 2015: Louis-Éric Trudeau finds that the brain cells his work, including the clinician-scientist award most at risk in Parkinson’s consume unusually from the Canadian Institutes of Health Research, high amounts of energy, gradually exhausting and the Prix de Jeune Chercheur Blaise Pascal, the killing themselves. EJLB Foundation Scholar Research Award and a National Scholar Award from the Fonds de la Neuroscientists at Sunnybrook Health Science Recherche en Santé du Québec. Centre use focused ultrasound to break through one of the human body’s final frontiers — the Current research studies include: blood-brain barrier — opening the door to • using cannabinoids for pain in Parkinson’s better treatments. • discovering new compounds that could be used as a radioactive tracer to allow researchers 2016: Michel Desjardins and Heidi McBride and clinicians to scan the brains of people with discover that two genes associated with Parkinson’s to measure the activity of a protein Parkinson’s disease are key regulators of the that may signal the presence of the disease immune system, providing direct evidence linking • examining the role that fungi in the gut may Parkinson’s to auto-immune disease. play in influencing Parkinson’s • mapping mutated forms of the Parkin gene, Jeremy Lee and Ed Krol design two chemical which causes the early-onset Parkinson’s compounds based on caffeine that could help in disease that people inherit, to help prevent or the fight against Parkinson’s. treat the disease

Since its founding in 1965, Parkinson Canada has aggressively funded innovative research for better treatments and a cure. The only organization that specifically funds Parkinson’s research in Canada, Parkinson Canada invests in Canadian research from the ground up through its national research program. Many projects are geared to the discovery stage, which lead to other funding opportunities and new treatments relevant to Parkinson’s disease. Since 1981, the research program has funded 528 research awards, fellowships and grants, totaling more than $27 million. Other Canadian Medical Advances in the Past 150 Years

University of Toronto begins the James Collip discovers the production of the first Canadian- parathyroid hormone, which helped 1925 made diphtheria antitoxin. 1914 increase the understanding of how our bodies regulate calcium concentrations and eventually led to new treatments for osteoporosis.

Wilder Penfield develops a surgical method for treating epilepsy, called

the “Montreal Procedure”. 1934 Hans Seyle coined the term the stress syndrome to identify the mechanism

1936 by which the body confronts stress — connecting stress with disease. Herbert Henri Jasper was a pioneer in establishing the

electroencephalogram (EEG), used to 1940 study electrical activity of the brain. Maud Menten performs the first protein separation using

1944 electrophoresis, which to this day is a standard research tool in genetics Raymond Parker discovers a and other biological sciences. chemical nutrient in which cells can

grow and replicate, playing a role in 1945 the discovery of the polio vaccine.

Canada was instrumental in the research and large-scale production

1955 of the vaccine against polio virus — using an incubation process referred to as the “Toronto Method”, which made it possible to increase the Thomas Chang was an undergraduate quantities of the virus for the trial. student when he invented the first

artificial cell in the world. 1957

Tommy Douglas was referred to as “father of medicare” for his

1966 contribution to the health care debate, which eventually resulted in Canada’s current health care system. Canadian freeze-dried smallpox vaccine developed by Connaught

Laboratories serves as the 1967 international standard for the global Bruce Chown licenses Rh smallpox eradication program. immunoglobulin, virtually

1968 eliminating Rh disease, which had claimed the lives of many babies.

Kelvin Kenneth Ogilvie develops the automated gene synthesizer —

referred to as the “Gene Machine” — 1980 Bruce Chown and Jack Bowman making it possible for scientists to develop Rhogam, which solved the manufacture DNA sequences within 1980 problem of Rh allo-immunization. hours rather than months. Rhogam contains antigens that have been shown to counter the antigens present in an Rh-negative mother, thereby protecting the developing fetus. This discovery has saved Bernard Belleau develops lamivudine, thousands of lives all over the world. a potent antiviral medication that

becomes an important component of 1989 HIV/AIDS treatment.

Sam Weiss discovers human neural stem cells — a ground-breaking

1992 finding since scientists believed the Michael Smith wins the Nobel brain cannot regenerate. This has Prize in chemistry for his discovery resulted in new approaches when it of a process called site-directed 1993 comes to brain cell repair. mutagenesis, which allows researchers to introduce specific mutations into genes.

Harry Jennings develops a highly effective synthetic vaccine,

2002 NeisVac-C, which protects people of all ages against meningococcal meningitis, a disease carried by the bacterium Neisseria meningitis. The vaccine is effective for babies as young as 2 months. Canadian researchers sequence the SARS genome in just 11 weeks, then

develop three potential vaccines 2003 and a treatment within a matter A vaccine for E. coli in cattle of months. developed by Brett Finlay and Andy

2004 Potter proves successful and is marketed worldwide.

Susan Bryson and Lonnie Zwaigenbaum develop the first autism observation scale for infants, 2005 Research directed by Lakshmi Kotra helping identify autism in children as leads to the discovery of a synthetic young as 6 months. 2007 compound that binds to and inhibits a key enzyme the malaria parasite needs to reproduce and survive.

Michel Desjardins and a team of Canadian and American researchers

discover a mechanism by which the 2009 body’s immune system can identify and attack the cold-sore-causing Type 1 herpes simplex virus. Mick Bhatia and colleagues discover how to convert human skin cells into

2010 blood cells.

Scientists identify a new cellular structure that appears to be responsible for previous 2015 Lewis Kay’s work in the field of unexplained rejection of organs. biomolecular nuclear magnetic

2017 resonance spectroscopy sheds light on how molecules involved in neurodegeneration can form abnormal structures that ultimately lead to disease.