The global burden of stroke and heart attack

Stroke and myocardial infarction (MI) are the world’s biggest killers. Each year, they are responsible for almost 30% of all deaths worldwide. Stroke is also the major cause of serious long-term disability. For heart attack patients, even if they survive, their heart is often irreversibly damaged. Long-term, this can lead to heart failure and ultimately the need for a new heart.

A major reason for these high levels of mortality and morbidity is the complete lack of approved drugs that target the tissue damage caused by stroke and MI. Although thrombolytic drugs are used infrequently in MI and stroke, they are designed to dissolve arterial occlusions without inhibiting the biochemical pathways already set in motion that lead to long-term damage to the heart and brain. Infensa Bioscience is the only company that is developing therapeutics that directly target the initial organ damage caused by both MI and stroke.

Acid-induced cell death during stroke and heart attack

The heart and brain are highly metabolically active organs that require oxygen to produce enough biochemical energy (ATP) to carry out their critical physiological functions. Thus, the loss of oxygen supply during stroke and MI is a life-threatening event for these organs. In order to salvage tissue, they switch to anaerobic glycolysis to produce ATP in the absence of oxygen. While this alternative method of fuel utilisation is critical to supply energy in the short-term, a failure to quickly re-establish oxygen supply leads to a build-up of lactate, the end-product of the glycolytic pathway. This is analogous to the build-up of lactate in your muscles during high-intensity exercise. Low heart and brain pH due to lactate accumulation are strongly correlated with mortality following MI and stroke, respectively.

The mechanisms by which tissue acidosis leads to cell death has been a subject of conjecture for decades, but recent breakthroughs by Infensa scientists and other groups have identified acid-sensing ion channel 1a (ASIC1a) as a key mediator of acid-induced cell death in both the heart and brain. ASIC1a is activated when the pH falls below 7, and this triggers cell death pathways that cause heart muscle cells and neurons to commit suicide. Infensa scientists have shown that inhibition of ASIC1a can greatly reduce tissue damage after stroke and MI.

Infensa’s ASIC1a inhibitors protect the heart and brain after stroke and myocardial infarction

Infensa scientists have developed patented molecules that inhibit ASIC1a with 20,000-fold greater potency than the most widely used blocker of this channel (the diuretic drug amiloride). These ASIC1a inhibitors have proven safe and highly efficacious in preclinical models of human MI and ischemic stroke. For example, in a model of human stroke, one of Infensa’s lead molecules reduced brain damage by 80% when administered 4 hours after stroke onset. Infensa is developing these molecules for treating MI and stroke patients in both hospital and ambulance settings, with an initial focus on patients that suffer a severe type of heart attack known as ST-elevation myocardial infarction (STEMI).