The heart is the body’s most important organ; ask any cardiologist or researcher who studies the organ and they will tell you dozens of reasons why that is the case. Its beating is one of the first detectable signs of life, which continues its steady drum until the very end of our lives. Its pumping drives the circulation of nutrients throughout the body, ensuring that every cell receives the fundamental molecules it needs to survive. It’s constantly syncing its beat to our day-to- day lives, often serving as the only physical indication of our own hidden emotions. When something goes radically wrong with the heart, or its related structures, our quality of life is drastically and negatively impacted. Unfortunately, cardiovascular disease is often silent in its development with incidences of the disease steadily rising to become the leading cause of death in the world.
Cardiovascular disease encompasses the collection of conditions that affect the heart or its associated blood vessels. Globally, it is the major cause of morbidity and mortality and it’s a burden that’s felt both physically, emotionally, and economically. Despite significant progress in treatment options, it is estimated that a heart attack occurs once every 7 minutes in Canada 1 . High cholesterol is associated with an increased risk of heart attack and is usually a result of a poorly maintained diet. High levels of cholesterol lead to the build-up of hard plaques lining the vessels, decreasing the supply of oxygen and nutrients to the heart. When the arteries narrow to a significant degree or when a plaque ruptures, blood flow to the muscles of the heart is disrupted causing the muscle tissue to die, an event called a myocardial infarction or better known as a heart attack.
Given its significance in human health, there have been great therapeutic advances made to help treat heart disease, including therapeutics that lower cholesterol. In fact, this growing epidemic has prompted the production of a wide-variety of therapies. In the past five years, more than 18 therapies have been approved by the FDA for the treatment or management of cardiovascular disease. 2 Scientists are continuously developing innovative medicines and are constantly improving the safety of drugs by designing them to target specific disease causing proteins. These drugs are often taken together to increase their effectiveness in treating heart disease.
Statins are a class of drugs designed to lower cholesterols by inhibiting a key enzyme (HMG-CoA reductase) involved in its production. Statins are used as a first-line of therapy for millions of people around the world, and are one of the most profitable drugs in pharmaceutical history. While they general have a good safety profile with minimal clinically significant side effects, a number of cholesterol-lowering drugs have been withdrawn from the market for causing serious adverse effects and, in some unfortunate instances, death.
The issue of statin-drug safety came to light when Bayer’s drug Cerivastatin (Baycol®) was voluntarily withdrawn from the market. The drug, when given in combination with Fibrates – another class of drugs used to treat hypercholesterolemia – increased the risk of developing life-threatening myopathies/heart conditions. This is an example of a drug-drug contraindication, whereby the two drugs involved act on the same protein target leading to intensified biological effects that can be potentially harmful. Contraindications can also occur when drugs share the enzymes responsible for their metabolism, creating a situation where a single drug is metabolized exclusively leaving the other in increased, potentially toxic, concentrations.
Cyclica’s Ligand Express™ platform is uniquely capable of detecting situations where two or more drugs may combine to cause a harmful effect. It does so by first predicting interactions between small molecules and all structurally characterized proteins. Using Cyclica’s proteome-wide screening and its systems biology toolkit, we are able to compare the predicted drug-protein interactions between two or more drugs likely to be prescribed in combination. This provides an efficient and cost-effective way of validating years of pre-clinical data and gives a better understanding of the interplay between two drugs. This tool may be used at any stage during drug discovery or post-market, however identifying serious adverse effects of combination therapy before entering the market can save lives and drug-development costs. Cyclica’s predictive capabilities guide experiments to test specific safety concerns, making drug discovery more efficient, and reducing the number of expensive late-stage failures.
1. Statistics Canada.Causes of Death, Canada, 2011.CANSIM data.Released January 28, 2014