© University of Pittsburgh
The University of Pittsburgh
The group of Prof. Dr. Guy Salama from the University of Pittsburgh, Department of Medicine, Heart and Vascular Institute and Relaxera are investigating the effects of relaxin-2 on myocyte stiffness by altering the structural protein titin in an animal model.
Cardiovascular diseases are the number 1 cause of death globally. CVDs include disorders of the heart and blood vessels, coronary heart disease, cerebrovascular disease, heart failure, and others. About 50% of patients with heart failure suffer from HFpEF, heart failure with preserved ejection fraction. Increased cardiomyocyte passive stiffness is part of the pathophysiology. This stiffness is largely due to modifications of cardiac titin.
Titin is the largest known protein consisting of more than 34,000 amino acids in humans and plays a major role for muscle contraction and relaxation. The cardio-specific titin N2B shows hypophosphorylation in HFpEF.
Can relaxin modify the expression levels of the dominant isoforms of titin (N2BA and N2B) or the phosphorylation status? Former studies (also in humans) have shown that relaxin-2 has anti-fibrotic effects on multiple organs including the heart, and its signalling via protein kinases A and G may well target titin phosphorylation status.
The relaxin effect will be measured by (amongst others) histological examinations on myocardial fibrosis, by skinned fibre experiments, biochemical examination of titin expression and phosphorylation, and by echo examinations with assessment of diastolic function. Inflammation markers will be examined as well.
This study could further establish relaxin-2 treatment as a potential therapy for HFpEF, until now the greatest unmet medical need in contemporary cardiology .
CBL (Chemical and Biopharmaceutical Laboratories) Patras
Relaxera and CBL Patras sign mutually exclusive agreement on manufacturing, marketing, promotion, and sales of human relaxin-2.
This cooperation agreement designates CBL as the exclusive manufacturing partner for synthetic human relaxin-2 and INSL peptides and Relaxera as the exclusive sales executive partner for relaxin-2.
CBL Patras, founded in 1990, is worldwide one of the largest peptide material suppliers offering proprietary and generic GMP and non-GMP peptides. Among them now as well relaxins and other insulin-like peptides. CBL is approved by European Authorities and FDA.
Relaxin-2 produced at CBL in Patras will be used by Relaxera to develop this peptide for cardio-vascular and metabolic diseases, dermatology, and other illnesses. Based on previous academic research, Relaxera has obtained trilateral (JP, US, EU) patents claiming protection for synthetic relaxin-2 for a treatment of heart failure with preserved ejection fraction and diabetes-related conditions, namely for prophylactic treatment of obese patients developing impaired glucose tolerance and prediabetes.
HFpEF – Heart Failure with preserved Ejection Fraction
HFpEF represents a distinct sub-entity of heart failure. Like heart failure in general, HFpEF is characterized by the inability of the heart to provide, at normal filling pressures, an output adequate to meet the physiologically varying demands of the body (Paulus 2007, The Task Force 2008). This causes the broadly known symptoms like dyspnea on exertion or even at rest, edema (fluid overload), organ dysfunction, and fatigue.
HFpEF is defined by an impaired diastolic relaxation of the left ventricular myocardium (synonym: diastolic dysfunction) which hinders ventricular filling. Despite this, the systolic performance of the left chamber, dependent of active tension development, remains largely normal. The compromised myocardial compliance and relaxation can be attributed to the following:
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