Heart failure: New drug candidate improves failing heart’s function

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Washington | Published: June 15, 2015 1:32:12 PM

A new study has revealed about an experimental drug that improves the ability of heart muscle cells damaged by heart failure to pump blood.

A new study has revealed about an experimental drug that improves the ability of heart muscle cells damaged by heart failure to pump blood.

Led jointly by researchers from the Cardiovascular Research Center and The Experimental Therapeutics Institute at Mount Sinai, the study has discovered a powerful molecule called N106, treatment with which increased heart muscle contraction to improve heart function so far in human heart cell and animal studies.

Lead researcher Roger Hajjar said that in the near future their multidisciplinary research team hopes to launch the first clinical trials to test this promising medicine in heart failure patients, adding that this first-in-class small molecule targets a known cellular pathway, improves heart failure cell abnormalities, and may provide an essential future treatment for these patients.

Heart failure occurs when the heart becomes too weak to properly pump and circulate blood through the body. N106 may counter this by directly docking to and activating an enzyme E1 ligase that turns up the function of another SERCA2a (Sarcoplasmic Reticulum Calcium ATPase).

SERCA2a is a critical protein responsible for the proper flow of charged particles (e.g. calcium) in and out of heart muscle cells, with the charge flow needed to drive muscle contraction. Abnormal calcium cycling and decreased expression of SERCA2a in heart muscle cells is a major hallmark of heart failure, forcing the heart to work harder and grow larger, even as it weakens.

Hajjar added that like most currently available drugs, the study compound, N106, is a “small molecule,” with a molecular weight low enough to efficiently diffuse into cells and have its effect. Treatments that are not small molecules include those based on antibodies, which are much larger and more complex (and often more expensive) than small molecules.

The study is published online in Nature Communications.

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