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US-based clinical stage biopharmaceutical firm has begun dosing in its Phase I single ascending dose clinical study of MYK-491 to treat dilated cardiomyopathy (DCM).

The oral small molecule MYK-491 is currently being developed in an ongoing collaboration between MyoKardia and Sanofi and is an allosteric modulator of myosin, which improves cardiac contractility in a DCM heart.

Designed for hypertrophic cardiomyopathy, MYK-491 acts on the underlying bio-mechanical defects of the heart muscle.

The randomised, placebo-controlled Phase I trial will evaluate the safety, tolerability, preliminary pharmacokinetics and pharmacodynamics of single ascending oral doses of MYK-491 in healthy volunteers.

The study will measure the potential changes in systolic ejection time, along with other established echocardiographic measures of cardiac contractility.

"The preclinical studies indicated that MYK-491 may increase the heart’s contractility, with minimal impact on diastole or relaxation."

MyoKardia chief medical officer Marc Semigran said: “There are currently no approved therapies that address the underlying bio-mechanical causes of DCM, which can lead to chronic, progressive, debilitating heart failure that can shorten life.

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“Preclinical research across many animal models has demonstrated that MYK-491 may increase the heart’s contractility with minimal adverse effects on myocardial diastolic function, which is also abnormal in DCM patients.”

DCM is characterised by thin and over-expanded left ventricle walls, which decreases the contraction, leading to insufficient blood pumping by the heart, shortness of breath, fatigue, swelling in the extremities, or an irregular heartbeat.

The preclinical studies indicated that MYK-491 may increase the heart’s contractility, with minimal impact on diastole or relaxation.

It is expected that the topline results from the Phase I study will be available in the third quarter of this year.