From left, John Ussher, assistant professor and Rami Al Batran, post doctoral graduate student, are researching drug therapies that are safe for treating cardiovascular disease and repurposing them to treat people with Type 2 diabetes.
Today is World Diabetes Day. Read how our researchers are investigating ways to treat this disease that impacts so many peoples' lives.
High drug development costs challenge researchers and pharmaceutical companies worldwide to look at new ways of using drugs that are already approved and safe to use.
Researchers look at existing, safe drug therapies to treat one disease and investigate if those same therapies can be repurposed to treat other diseases.
John Ussher, assistant professor in the Faculty of Pharmacy and Pharmaceutical Sciences and his research team are using this approach to discover novel treatments for Type 2 diabetes by using approved drugs for other conditions (such as heart disease) in new ways.
Ussher and his research team are looking at drug treatments commonly used to treat cardiovascular disease, the number one cause of death in patients with Type 2 diabetes. His team is studying if that same drug can treat people with Type 2 diabetes,
According to the Canadian Diabetes Association, 3.9 million Canadians live with diabetes.
He says the challenge is to develop a drug that improves both hyperglycemia and insulin resistance - the number one predictor for the future diagnosis of Type 2 diabetes - but that also doesn't worsen a patient's cardiovascular disease. The drug has to be as good as other drugs on the market at improving blood sugar for Type 2 diabetes patients. At the same time, though, it can't be worse than these drugs with regards to their actions on heart function and heart disease risk.
"Our research is based on the premise that there are drugs that help people with Type 2 diabetes, that treat insulin resistance and those are proven at a clinical level," says Ussher. "But, the key is that we need to do more research to make sure they are safe for the person's heart."
"While safety for both conditions is always a concern, the main issue in drug development for Type 2 diabetes these days is the need to prove safety for heart disease, even if drug is very good at improving blood sugar control in a diabetic but worsens risk for heart disease, chances are drug will not be approved for diabetes. Thus the reason we are using drugs already approved for heart disease, if they have secondary effects that improve blood sugar control, they may be ideal drugs to use for patients with Type 2 diabetes as chances are they will not increase risk for heart disease in this population."
Ussher says the drug therapy he and his team are studying has been proven to safely treat people with the cardiovascular disease, angina, and now they're testing if it is beneficial for treating Type 2 diabetes.
He notes that drug development is expensive often requiring billions of dollars in funding, years of research and clinical trials and this makes drug development very time consuming and expensive.
Ussher says both obesity and Type 2 diabetes increase the risk for people developing cardiovascular disease.
"A majority of people who have Type 2 diabetes will eventually die from heart disease," says Ussher.
According to two studies (Impact of diabetes on coronary artery disease in women and men: a meta-analysis of prospective studies published in the Diabetes Care Journal - 2000 and Relation between age and cardiovascular disease in men and women with diabetes compared with non-diabetic people: a population-based retrospective cohort study published in Lancet - 2006), 65 to 80 per cent of people with diabetes will die from cardiovascular disease, compared to people without diabetes.
"What we did is narrowed our research to a drug therapy used to treat cardiovascular disease, specifically angina. We didn't specifically target angina, but angina is a condition associated with coronary artery disease which many patients with Type 2 diabetes also have or are at risk for, and based on 1 of the mechanisms by which the drug is predicted to work for treating angina, we thought it would translate favourably for improving blood sugar in Type 2 diabetes patients."
Ussher and his team, including post-doctoral fellow Rami Al Batran, are testing their novel therapy on mice populations . Through the first two cohorts, the results are very promising. His research team conducted a glucose tolerance test in both obese and non-obese mice to determine if the drug could improve the clearance of sugar from their bodies. "We conducted the treatment as a reversal protocol, so we made the mice obese and insulin resistant first, then we treated them with the drug. The result was that we were able to greatly improve how effectively the obese mice cleared the blood sugar during the glucose tolerance test."
Ussher says he set up his study in this way because many patients who need to take these medications are already living with obesity and Type 2 diabetes, so if it works in the lab, it's more translatable.
"We've conducted two studies on male and female mice and we saw that the test drug we uses help clear the sugar from their bodies and it was the same result in both males and females. From a researcher's perspective, these two trials gave me confidence that there is a real biological change, that this drug, originally intended to treat angina in cardiac patients, also lowers blood sugar levels."
Ussher says one surprising result that came as a result of this study was the drug was also decreasing body weight and fat mass. "We did not expect to see this at all," he says. "This is so important and we are trying to identify why this is happening - what is the trigger or mechanism that is responsible for this unexpected action."
He says because obesity increases the risk for both Type 2 diabetes and cardiovascular disease, understanding why the drug is lowering body weight is important because it can be an independent mechanism contributing to the improvement of blood sugar levels and improvement of cardiac function in patients taking this drug.
Ussher and his team are completing one final cohort, gathering the data and trying to identify whether changes in energetics (the ways cells/organs burn fuels to produce energy for the body) are actually involved or is it some other unidentified mechanism.
Ussher says his approach to this research is unique and may signal the way Type 2 diabetes research is conducted in the future. "I don't think anyone else is taking the exact same approach as we are in this scenario, but as drug development for Type 2 diabetes has become more challenging, I think there's going to be a trend in coming years of looking at drugs that are already approved and safe for humans and seeing if they have beneficial effects for diabetes too."
Ussher sees this new drug therapy benefitting a segment of a patient population that has Type 2 diabetes and heart disease. "The drug treatment wouldn't necessarily be for every Type 2 diabetes patient, but it might be the right therapy for a patient that suffers from both conditions. It would help greatly when it comes to patients who are on multiple medications because it's already dealing with two conditions. It could potentially reduce the need for two medications, instead of this one."
He credits his research team, specifically researcher Rami Al Batran, for getting the research study started and with its progress to date. Al Batran, whose graduate work was in cardiovascular disease, has a special interest in diabetes research.
"In Syria, where I grew up, my father was a cardiologist and my grandmother had diabetes, so from an early age, I was comfortable with the language around those two areas," says Al Batran, who joined the lab in 2015. "Diabetes research is a very promising field of study and with the new techniques we have learned here in our labs, the results of our work look promising."
Ussher says the 12-month study will come to a close but the project will continue. His hope is to publish his results in 2017 and pursue other questions surrounding this research into treating Type 2 diabetes.
"The study of obesity in people is important," he says. "We started with an idea, then we developed it into a research project and then hopefully this leads into a full fledged program someday. My hope is that the research community involved in diabetes and heart disease research would take interest in this and it would invigorate research and interest in simultaneously tackling the issues of both Type 2 diabetes and cardiovascular disease."
Ussher hopes other research teams worldwide would take interest in this study and help try to unlock how this drug creates this dual benefit, or if other drugs already approved for cardiovascular disease may harbor this same type of dual benefit.