Significant research underway at the University of Saskatchewan is grabbing international attention, as it has the potential to help millions of people in Canada and across the world who are affected by allergies, asthma and autoimmune diseases.
A group of researchers on campus has developed an immunotherapy technique that reverses food allergies in mice, which has the potential for positive results in humans as well. The team is headed by Dr. John Gordon, who is a research leader of the Canadian organization AllerGen Networks Centre of Excellence, the vice-president of the Canadian Society for Immunology and a professor in the department of medicine on campus.
Although the most recent findings were published in October 2016 in the Journal of Allergy and Clinical Immunology, Gordon has been involved in this research for 12 years and explains what it is that the team has discovered.
“In essence, we have developed a cellular therapy by which we can reverse allergen sensitivity in mice that are allergic to egg proteins and peanuts. We’ve shown previously that we can also do this type of thing in mouse models of asthma and with allergic cells from asthmatic individuals, but using a slightly different type of dendritic cell, and that was also relevant in a mouse model of multiple sclerosis,” Gordon said.
In 2010, the research team took blood cells from asthmatic individuals and converted them into tolerance-promoting dendritic cells in a test tube. They then used these new cells to convert asthmatic, or Th2 cells, into regulatory cells, which switch off the rest of the asthmatic cells in the blood cell donor.
This means that the researchers are trying to replace the damaging responses seen in those who have allergies with the non-aggressive or tolerant responses seen in those who do not have allergies. Dendritic cells are important for the immune system and are present in all tissue that comes in contact with the external environment, such as the skin and the lungs.
“Only 20 per cent of the population has allergies, while the other 80 per cent don’t, despite the fact that in spring time, for example, both groups are equally exposed to allergens,” Gordon said. “For the 80 per cent that don’t have allergies, their own lung dendritic cells take the inhaled pollen, for example, and show it to immune cells with instructions indicating that, ‘We don’t need to get aggressive about this, we just need a regulated response.’ So these dendritic cells activate the body’s regulatory T-cells, and so you don’t get an allergic response.”
In contrast, the remaining 20 per cent of the population do develop an allergic response, as their dendritic cells tell the immune system that the allergen is a dangerous pathogen that needs to be attacked, culminating in an allergic reaction.
Gordon and his team have found a way to convert those Th2 cells in allergic individuals into regulatory cells, which suppress the individual’s allergic response by up to 90 per cent. This process can be applicable in a number of settings.
“In principle, it could work for many immunologic diseases — and that includes allergies — from atopic dermatitis to food allergies and asthma, but also into autoimmune diseases like multiple sclerosis,” Gordon said.
According to a 2010 nation-wide study published in the Journal of Allergy and Clinical Immunology, one in every 13 Canadians suffers from a food allergy, the most common being peanuts, other tree nuts, eggs, seafood, soy and sesame. This does not even take into account those who also suffer from seasonal and environmental allergies as well.
Lara Witt, a bachelor of science honours student in physiology and pharmacology and a member of Gordon’s research team on campus, notes what this discovery would mean for people with allergies.
“If this research becomes a medical reality, patients will be able to cure their asthma and allergies … Patients will no longer need to utilize the typical treatments; these can be inconvenient, expensive in the long-term and often have unsavoury side-effects when taken regularly. Additionally, acute care in this field will also all but cease to exist. The unreasonable price of EpiPens has been in the news lately; this therapy could potentially make EpiPens, as well as all other current emergency treatments, obsolete,” Witt said.
While the impact of such research would be incredibly positive for those who do have allergies, it could also benefit those with asthma. A chronic inflammatory disease of the airways, asthma is characterized by a shortness of breath, coughing, tightness in the chest and wheezing. According to the Asthma Society of Canada, asthma affects over three million Canadians.
Gordon notes that this research could also reduce the cost of Canadian healthcare.
“There’s an incredible human side to solving food allergies because of their capacity to be lethal,” he said. “But also, direct and indirect costs of asthma in Canada cost us somewhere between $1 and $2 billion per year. So if you could reduce that, it would have a significant impact on our healthcare system.”
Canada also has the highest rate of multiple sclerosis in the world, with the MS Society of Canada reporting that approximately 100,000 Canadians are living with the disease. Multiple sclerosis is a disease that attacks the protective covering of the nerves, called myelin, causing inflammation and damage to these coverings. Myelin is crucial for the transmission of nerve impulses through the nerve fibres in the body, and as it stands, there is currently no known cause or cure for it.
Witt believes firmly in the research project, noting that she thinks immunotherapy is the future for allergies, asthma and autoimmune diseases — and she is not alone. Christopher Rudulier, who is also involved with the research and is a fourth-year post-doctoral student at the U of S, completed his PhD in immunology in 2012 and finds this current research fascinating.
“The most interesting aspect of the research to me is the broad applicability of our regulatory dendritic cell approach to allergy. These regulatory dendritic cells are immunosuppressive in that they actively ‘turn off’ unwanted immune responses. So, in principle, any allergy can be targeted by putting the relevant allergen — cat dander, egg protein, fish protein, etc. — into the dendritic cell. Additionally, regulatory dendritic cell therapy has the potential to be curative as it ‘turns off,’ or corrects, the immune response driving the allergy,” Rudulier said.
Gordon and his research team have been talking to Health Canada for a year now, and they are on board with the project. Moving forward, however, the team needs to acquire funding and to make sure that their process is safe for testing on individuals before Health Canada gives full approval.
“What we need to go into people [for testing] is the ability to generate good manufacturing practice, or GMP, cells. Those are ones you can put into people without worrying if [the cells are] contaminated at all. So we need the capacity to generate those cells, and once we can do that, and Health Canada is satisfied that we have good protocols in place, then they would give us permission to [move forward] with putting them into an individual to make sure it doesn’t have any adverse effects,” Gordon said.
If everything lines up perfectly, the team could be ready to start testing on individuals in a year from now. Gordon mentioned that they already have six of Canada’s leading allergists in place, who are ready to move forward with clinical trials on individuals once the project is approved by Health Canada. The team has also been collaborating with other universities, such as McGill University and Stanford University, along with other departments at the U of S.
The collaboration range is wide, and Rudulier notes this is partly due to the fact that the research taking place is rare.
“The type of work being conducted by Dr. Gordon is rather unique in Canada. I think that using Dr. Gordon’s work to attract other researchers working on allergy immunotherapy could have a tremendous impact on the university,” Rudulier said. “In addition, and perhaps more importantly, building a program centered on immunotherapy for allergy, where a number of researchers are working on the same problem, has the real potential to increase the rate at which these groundbreaking discoveries are made, which in turn has the potential to impact the lives of people with these devastating allergies.”
For Gordon, having this research come to the limelight after all these years would be incredible.
“I’ve been working on this for a long time … I’m a researcher, my heart is in the research. To me, seeing this go forward, and particularly come out of Saskatchewan, would be a wonderful thing.”
Naomi Zurevinski / Editor-in-Chief
Inforgraphics: Lesia Karalash / Graphics Editor