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Health research can be a slow process. Sometimes there are big breakthroughs that change outcomes quickly and sometimes progress is built on a series of steady improvements. We’ve seen both breakthroughs and steady progress in cystic fibrosis (CF) research. Over the last 50 years, the life expectancy of a child with CF has increased a remarkable 10 fold, from four years to over 48 years! Not only is life longer, but the quality of life has been vastly improved for these individuals. This is a direct result of the incredible work of scientists and clinicians who have dedicated their lives to seeking greater understanding of the disease and improving treatments for our patients. Contributing to that progress is the discovery here at SickKids, over 25 years ago, of the genetic mutation that causes CF, work that has laid the foundation for our current development of new therapeutics. May is Cystic Fibrosis Month and this issue of our enewsletter explores SickKids’ contributions of the past, present, future to fighting and beating this disease.
The Tsui Lab: Dr. Batsheva Kerem, Dr. Lap-Chee Tsui and Dr. Johanna Rommens on September 8, 1989 - the day the Science paper on the CFTR discovery was published.
In 1989, after almost a decade of research, Dr. Lap-Chee Tsui and his team of scientists at SickKids identified the gene responsible for causing cystic fibrosis, a medical discovery that is understood to be one of the most significant breakthroughs in human genetics in the past 50 years. Mutations in the CF trans-membrane regulator (CFTR) gene were found to cause cystic fibrosis, the first ever disease-causing gene to be identified using only family studies and chromosome location information.
Following the CFTR gene discovery, members of this world-class team have continued conducting ground-breaking research in the field of CF at SickKids and around the world.
Dr. Johanna Rommens, Dr. Lap-Chee Tsui and Dr. Batsheva Kerem in the Vice Chancellor’s Office at the University of Hong Kong, December 2013.
Tsui established a mutation database which collected 1,900 mutations of the CF gene that scientists around the world could access for the most up-to-date genetic information about the disease. In 2002, he was appointed Vice-Chancellor and President of the University of Hong Kong, a role he held until the end of 2015. Tsui remains connected to SickKids through his role as Adjunct Scientist.
Dr. Johanna Rommens is currently a Senior Scientist at SickKids and Professor of Molecular Genetics at the University of Toronto. Her research laboratory has been focused on genes that lead to various genetic diseases, but remains active in the field of cystic fibrosis and understanding how ‘modifying genes’ influences severity of disease presentation. She works alongside Drs. Christine Bear and Stephen Scherer, both senior scientists at SickKids and former colleagues from Tsui’s lab at the time of the gene discovery.
Dr. Batsheva Kerem went on to establish her own lab at the Hebrew University of Jerusalem, which is also focused on CF research. Specifically, Kerem’s lab is interested in investigating the repertoire of CFTR mutations among Jewish and Arab populations, and the effect of these mutations on disease severity.
Madi Vanstone and her dog Izzie at their family farm in Beeton, Ontario.
Madi Vanstone was diagnosed with cystic fibrosis (CF) in 2002 when she was just eight-months-old and has been back and forth to SickKids since. Fourteen years later, Madi is a frequent visitor to SickKids and the CF clinic and has made a huge splash within the CF community.
Madi’s advocacy began in 2014 when she was 12-years-old and began taking a medication called Kalydeco for her rare form of CF. “Kalydeco corrects the defective CF gene in my body and allows me to do all the things that I love to do,” Madi shared. “It’s almost like a cure!” But because this drug was costing Madi and her family $348,000 a year, she began to advocate for OHIP coverage of Kalydeco.
Three trips to Queens Park, a meeting with Premier Kathleen Wynne and the Minister of Health and Long-Term Care at the time, and one year of patiently waiting later, Kalydeco was 100 per cent covered by OHIP and Madi was credited with getting Ontario to fund this medication. Her efforts did not go unnoticed and she was awarded the International Teen Advocacy Award from Global Genes, Teen Champion of Hope Award from CF Canada, Outstanding Youth Philanthropist Award from the Association of Fundraising Professionals and Youth Leadership Award from the Canadian Organization for Rare Diseases.
She is a member of multiple advocacy groups and has been invited to speak at conferences all over North America where she likes talking about the positives and negatives of living with CF.
“Living with CF is hard because you have to give up a lot of activities; but it isn’t all bad! I’ve got to meet a lot of cool people and have made some great friends” said Madi. Her mom, Beth, shares that although she loves Madi’s positivity, it is important to share the impact that CF has on an individual and their family. “I love Madi’s version of her story but it is important to also share how it affects her and our family and the day-to-day challenges she has to live with,” Beth said.
What would a world without CF mean to you?
“I have a lot of friends who have lost the battle, so a world without CF would mean a world with them back in,” shared Madi. “My life without CF would mean no more hospitalizations, no more IVs and no more treatments. I wouldn’t have to worry about the scarring on my lungs increasing as I am getting older or worry about this challenge getting harder as the years pass by.”
Beth shared how thankful they are for everything SickKids has given them the past 13 years. “We definitely have a cup half full perspective on life and when we look at our cup, SickKids is part of our full.”
In a disease that presents with over 2,000 gene mutations, every cystic fibrosis (CF) patient is unique. A drug that works on one patient, may have a completely different effect on another patient. Targeted therapies, personalized to each individual patient, provide the most effective treatment. A strategic partnership between CF Canada and SickKids is working to do just that for patients with CF.
The Program for Individualized CF Therapy at SickKids, created because of this partnership, will build an international resource dedicated to individualized drug discovery in CF. Combining existing expertise in CF care and research, genetics and stem cell research at SickKids, this program will begin by creating model systems of 100 CF patients, with the hope of expansion in the future. These patients, both paediatric and adult, will provide a blood sample and have a tissue swab taken from inside their nose. With these samples, researchers will be able to conduct what they are calling ‘a clinical trial in a dish’ and create stem cells which they will turn into lung cells, pancreas cells and bile duct cells, the main areas in the body affected by cystic fibrosis. They will then be able to test, in the lab, how each patient reacts to each treatment, before the patient begins taking the drug. The goal is to determine if these laboratory based ‘clinical trials in a dish’ will predict which drug should be used for each patient. These trials in a dish can also be used to compare new drugs to existing drugs. The success of this approach will enhance the quality of life for patients by ensuring that they will take the drug which is best for them.
Another key feature of the project is the development of an electronic specimen tracking system to ensure these cell systems are accessible, through a robust biobanking system, not only to researchers at SickKids but to other researchers in Canada and around the world.
“I was at an international CF meeting in Europe recently and all in attendance were excited about this possibility. Nothing like this currently exists,” said Christine Bear, Senior Scientist and Co-Director of the Cystic Fibrosis Centre at SickKids and Professor of Physiology at the University of Toronto. Not only will the biobanking system be available to all, but SickKids will be conducting workshops where researchers from around the world can come and learn how to use these cell systems.
This project will have an impact on the whole CF community from researchers to clinicians to patients and their families. It will change the future course of the disease, determining the best medication on an individual patient basis.
“We want to be able to better make the link from the lab to actual health outcomes in patients.” said Bear. “Through this project we are making sure the right therapies get to the right patients.”
Learn more about the Program for Individualized CF Therapy at SickKids.