Heart failure is one of the leading causes of death worldwide. Affected patients suffer from a restricted pumping function of the heart, which leads to breathlessness, loss of performance and water retention. Despite existing medication, the need for treatment remains high. The new peptide S100A1ct could represent a promising alternative or supplement here. It consists of a short chain of amino acids that serve as natural building blocks of proteins and play a central role in biological processes.
Innovative mode of action of S100A1ct
The peptide is based on the natural protein structure of S100A1, a central regulator of heart function. The scientists synthesised a specific section of this protein that mimics the positive effects of S100A1 but can be used as a stand-alone drug. S100A1ct specifically improves calcium processing in the heart muscle cells by improving the function of the SERCA2a pump, which is responsible for calcium transport in the heart muscle cells, and the ryanodine receptor (RyR2), which controls the release of calcium. This leads to an improved contractility of the heart and a reduction in cardiac arrhythmias.
Positive results in preclinical tests
S100A1ct has been successfully tested in extensive preclinical studies. Administration of the peptide led to a significant increase in cardiac contraction both in isolated heart muscle cells and in animal models. In addition, animals with heart failure showed a better prognosis and an increased survival rate after administration. A rapid and sustained improvement in cardiac function was demonstrated after a single administration. Long-term tests over several weeks also showed no evidence of undesirable side effects or organ damage.
Potential for future therapy options
The study results suggest that S100A1ct could be a promising new approach for the treatment of heart failure. It is particularly interesting that the peptide works independently of classic beta-blocker therapy and could therefore also be used in patients with existing standard therapy. Thanks to its anti-arrhythmic properties, it could also help to reduce dangerous cardiac arrhythmias.
Further clinical studies are needed to investigate the safety and efficacy of S100A1ct in humans. If the positive effect is also confirmed in these tests, the peptide could play an important role in the treatment of heart failure in the future.
The study was conducted under the direction of Dr Patrick Most and Dr Julia Ritterhoff and their team at the Department of Molecular and Translational Cardiology at Heidelberg University Hospital. The research was supported by national and international funding and scientific collaborations.
Original publication:
Kehr D, Ritterhoff J, Glaser M, et al. S100A1ct: A Synthetic Peptide Derived From S100A1 Protein Improves Cardiac Performance and Survival in Preclinical Heart Failure Models. Circulation. Published online November 21, 2024. doi:10.1161/CIRCULATIONAHA.123.066961
