Researchers at Cytokinetics, Inc., Hopkins, CV Dynamics, Inc., the New Jersey Medical School and the University of Pennsylvania think they may have discovered the future of cardiac care for heart failure.
A team of scientists, led by Fady Malik of Cytokinetics, Inc. and including David Kass of Hopkins, has demonstrated the efficacy of a drug called omecamtiv mecarbil.
The drug, which is considered a small and potent activator of cardiac function, improves upon the current standard of drug treatments for cardiac care because it more directly stimulates cardiac myosin and is thought to have fewer side effects than current therapeutic pharmaceuticals.
As Fady Malik wrote in an e-mail to The News-Letter, “In systolic heart failure, the central problem is that the contractility of the heart is reduced. Prior attempts to improve cardiac contractility involved mechanisms that have several effects on the cardiovascular system — some of them not so good for people with heart failure. We believe that directly activating myosin is the most selective way to increase cardiac contractility and hopefully avoids many of these undesired effects of other mechanisms.”
Omecamtiv mecarbil acts, as was previously mentioned, by direct interaction with cardiac myosin. Myosin is a protein necessary for the contraction of muscles — in this case, the heart muscles. By binding to myosin, omecamtiv mecarbil seems to be able to facilitate binding between myosin and another protein called actin.
This is a particularly important capability, as it is the binding of myosin to actin that results in the “power stroke” that occurs in muscle fibers, causing them to contract.
In the heart, contraction is the driving force for pumping blood, so omecamtiv mecarbil’s ability to increase heart muscle contraction capabilities is crucial for keeping the heart working for patients suffering from systolic heart failure. More than just simply keeping the heart working though, omecamtiv mecarbil seems to be able to actually increase the efficacy of individual beats of the heart so that more blood can be pumped without significantly increasing the amount of work the heart must do.
“The drug increases the time the heart spends contracting during each heart beat and thus it leads to the heart ejecting more blood,” Malik wrote. “In essence, the heart does exactly what it would do in the absence of the drug but towards the end of contraction, instead of stopping, it continues contracting for a bit longer and continues to eject blood. In doing so, it doesn’t increase the oxygen consumed by the heart and so efficiency is increased (more blood pumped without a change in energy consumption [equals an] increase in efficiency).”
The heart is necessarily weakened by heart failure, and yet in response the body will try to increase the heart’s activity by increasing the tone of heart muscles almost constantly; this, accompanied by secretion of neurohormones, causes even more stress to the heart muscles. Thus, the potential ramifications of the present study are very promising, but Malik is cautious to assume too much.
“We hope that this property [of omecamtiv mecarbil] will be less stressful to the heart but that conclusion can’t be made until we show the drug has a clinical benefit in patients,” he wrote.
For now, Malik and colleagues must move forward from this experiment, which has already shown that omecamtiv mecarbil works in humans.
The next step will be to evaluate the benefits of treatment against any and all costs to assess feasibility of large-scale treatment and availability.
“We certainly hope that this novel drug mechanism will lead to improvements in the lifespan of patients with systolic heart failure and reduce their need for hospitalization,” Malik wrote.
He also notes that if omecamtiv mecarbil does live up to Malik’s and colleagues’ hopes it could potentially become a standard treatment option — and a potentially very effective one, at that. Malik is optimistic for that possibility.
“Heart failure is an extremely common condition with a mortality that exceeds that of many cancers. Any improvements in the condition of these patients could reduce health care expenditures on this condition,” he wrote.
Not only that, future testing with omecamtiv mecarbil may even prove that this drug is useful for activating a variety of muscles, which may make it the perfect drug treatment for diseases of skeletal muscle weakness and fatigue — or so Malik and his team hope.
