Overview
Most medical treatments are designed for patients in a one-size-fits-all-approach, which may be successful for some patients but not for others. Personalized medicine is an innovative and emerging field that utilizes an individual’s genetic profile, environment and lifestyle to guide decisions related to the prevention, diagnosis and treatment of disease to provide the right dose of the right drug at the right time.
Personalized medicine research at London Health Sciences Centre Research Institute (LHSCRI) is focused on understanding the molecular mechanisms of interindividual variation in drug response. This variation in drug response has long been a hindrance to obtaining effective and safe drug therapy. Differences in a patient’s response to drugs can lead to severe drug toxicity in some or loss of drug efficacy in others. These unexpected responses not only lead to suboptimal patient care but also result in an increased burden on overall health-care costs.
Pharmacogenomics seeks to relate genetic variability to variability in drug response. Our laboratory uses a pharmacogenomics approach, combining research on drug metabolism and transport with research on the influence of genetic variation on drug response, to develop personalized drug therapies for cancer, vascular disease and adverse drug reaction prevention.
To date, our research has helped to tailor drug therapies for over 10,000 patients.
Our Goal and Objectives
Goal
To combine research on drug metabolism and transport with research on the influence of genetic variation on drug response to develop personalized drug therapies that maximize the potential for therapeutic benefit and minimize the risk of adverse side effects for any given medication.
Objectives
- To discover new genetic polymorphisms that contribute to patient variation in drug response;
- To investigate new and exciting methods in the fields of pharmacogenomics, pharmacokinetics and pharmacodynamics, including the role of rare genetic variation in drug metabolizing enzymes and transporters; and
- Translate the latest advancements in pharmacogenomics-based personalized medicine approaches to the care of our patients.
Research Groups
Our personalized medicine research has focused on the following areas:
Direct Oral Anticoagulants
Heart attacks and strokes are major causes of death in many Western countries. To help prevent and treat these conditions, physicians often use anticoagulants, which are medicines that stop blood from clotting too much. For many years, a medicine called warfarin was the main choice for long-term treatment.
Recently, new medicines called direct oral anticoagulants (DOACs) like apixaban, rivaroxaban, and dabigatran have been introduced. These new options are easier to use and solve some problems that come with warfarin. However, physicians have noticed that the amount of these drugs that works in different patients can vary, and it’s not always clear why.
Our research aims to measure how much DOAC is in patients’ bodies in real-life situations. We want to find out what factors, like health conditions or genetics, might affect how well the drug works. This information will help doctors choose the right dose for each patient, making sure they get the best treatment possible.
Statins
Statins are the most commonly used medicines in North America to lower high cholesterol. They work by blocking an enzyme called HMG-CoA reductase, which helps make cholesterol in the body. However, about 10 to15 per cent of people taking statins report having muscle aches and weakness, which can make it hard for them to keep taking the medication.
Our current research aims to find out what other health or genetic factors might affect how well statins work for different people. We’re also studying how food affects the way the body absorbs rosuvastatin. We think that taking rosuvastatin with food might help it get into the liver better, which could mean less of the drug reaches the muscles. This might help reduce the muscle pain some people experience. Additionally, we’re looking into how bile acids might play a role in this process, which could lead to new treatments that help statins work better without needing food.
More than 10 years ago, our team noticed a need to help prevent serious side effects from certain chemotherapy drugs like 5-fluorouracil (5-FU) and capecitabine. We learned that a problem with an enzyme called dihydropyrimidine dehydrogenase (DPD) could lead to life-threatening reactions when people took these medications.
In 2013, we began testing for the DPD gene and giving doctors recommendations on how to adjust doses. By 2016, many doctors were asking us to test nearly all patients before they started treatment with 5-FU or capecitabine. Over the last 10 years, we’ve tested over 3,000 patients at our medical centre.
In 2018, we asked for official approval to make DPD testing a routine step before these chemotherapy treatments. Experts reviewed the research and in April 2023, Ontario Health approved DPD testing as a standard test in hospitals across Ontario. This shows how our research has directly improved patient care.
We also have ongoing collaboration with paediatric hematologists for pharmacogenetic testing for preventing toxicity to 6-mercaptopurine, a chemotherapy medication widely used for the treatment of childhood leukemia.
Inflammatory bowel disease (IBD) includes conditions like Crohn’s disease and ulcerative colitis, which cause long-term inflammation in the intestines. IBD can have a significant impact on people’s lives. Canada has one of the highest rates of IBD in the world, with over 233,000 Canadians affected or about one in every 150 people. Since 2001, the number of new cases has been increasing, especially among children.
Currently, there is no cure for IBD, so doctors use medications that help control the immune system. Patients often need to take these drugs for a long time, but not everyone responds well, and it is unclear why some people don’t.
We don’t fully understand how drugs are processed in people with IBD. By using advanced technologies like liquid chromatography and mass spectrometry, along with genetic studies, we hope to learn more about how IBD affects drug metabolism, in adults as well as in children. This knowledge could help improve the effectiveness of treatments and reduce side effects.