Chronic Heart Failure (HF) affects more than 26 million people globally. Over six million adults in Canada and the United States suffer from chronic heart failure and it remains a leading cause of death and hospitalization, with associated healthcare costs exceeding $30 billion annually in the U.S. alone.
People with HF suffer from shortness of breath, rapid heart rate, edema, reduced exercise capacity, often struggle with simple daily activities, and are frequently hospitalized. For many, these symptoms significantly reduce quality of life.
Heart failure occurs when the heart is no longer able to pump blood sufficient for the body’s needs.
Normal Heart Function
Two Types of Heart Failure
In heart failure with reduced ejection fraction (HFrEF), also known as systolic heart failure, this results from reduced contraction of the left ventricle such that not enough blood is pumped into the circulation. In heart failure with preserved ejection fraction (HFpEF), also known as diastolic heart failure, the left ventricle becomes stiff and does not relax normally. As a result, it cannot fill properly, and pressure begins to increase in the left heart chambers and in the lungs. The increased pressure in the lungs is the cause of shortness of breath.
HFpEF is associated with several co-morbidities including obesity, hypertension, diabetes, and older age. It is thought that HFpEF involves activation of the coronary micro-vascular endothelium (the lining of the small blood vessels in the heart) driven by a systemic pro-inflammatory state resulting from these co-morbidities. This systemic inflammation-induced endothelial dysfunction and activation leads to leakage of inflammatory cells from the circulation into the cardiac tissue. The subsequent production of a series of cytokines and increased oxidative stress leads to increased fibrosis, stiffness, and may impair cardiac contractile cell function.
There have been no significant treatment advances in HFpEF in the past 20 years; the primary therapy remains diuretics. Cardiol is dedicated to improving patients’ outcomes with innovative nanotherapeutics that target anti-inflammatory drugs to areas of cardiac tissue having significant inflammation and increased fibrosis.
CTX01 is a proprietary formulation of pharmaceutical cannabidiol being developed for the treatment of heart failure with preserved ejection fraction.
Published third-party research has shown that cannabidiol reduces inflammatory activation of the endothelial lining of blood vessels and aids endothelial vasorelaxation, resulting in improved blood flow. Cannabidiol has also been shown to attenuate a number of measures of inflammation in models of diabetes, a common co-morbidity in heart failure patients, and to reduce myocardial fibrosis in a model of inflammatory heart disease.
Cannabidiol is lipid soluble, virtually insoluble in water, highly sensitive to deactivation in the liver via first-pass metabolism and is rapidly cleared from the body. This results in low active blood levels and overall bioavailability of less than 10% when taken orally. Cardiol’s CTX01 formulation for subcutaneous administration is designed to avoid first-pass metabolism, optimize and maintain blood levels of the drug, and target cannabidiol to areas of inflammation and increased fibrosis in the heart. Cardiol believes that overcoming the low bioavailability issues associated with cannabidiol and targeting the drug to sites of disease, will significantly broaden the therapeutic potential of this molecule.