36 results about "Cardiac myosin" patented technology

Certain substituted sulfonamide derivatives of Formula I selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Certain substituted benzamide derivatives selectively modulate the cardiac sarcomere, for example by potentiating cardiac myosin, and are useful in the treatment of systolic heart failure including congestive heart failure.

Methods and compositions for rapidly replacing cMyBP-C in sarcomeres featuring the creation of Spy-C mice, which are mice genetically engineered to express cMyBP-C with a protease recognition site and SpyTag peptide introduced into the cMyBP-C gene. In permeabilized myocytes from the Spy-C mice, the cMyBP-C protein can be cleaved at the protease recognition site, and the N-Terminus of cMyBP-C can be removed while the C-terminus remains anchored to the thick filament. A new peptide featuring the SpyCatcher sequence can be covalently bonded to the remaining portion of cMyBP-C, thereby creating a modified cMyBP-C protein. The methods and compositions of the present invention allow for the reconstitution of full-length cMyBP-C at the precise position of native cMyBP-C in the sarcomere and allow for a variety of modifications to be introduced to cMyBP-C in situ.

The aim of the invention is to produce, in vitro, monoclonal antibodies against cardiac epitopes of the human My-C by generating myeloma cell clones, which produce said specific antibodies with epitope specificity. Said monoclonal antibodies should, amongst other things, enable an ELISA (Enzyme-Linked Immuno Sorbent Assay) for the specific, cross-reactivity free quantitative determination of My-C in serum, plasma or full blood, to be formed. Said aim is achieved by generating a hybridome cell clone which produces a monoclonal antibody which recognizes and binds with a cardiac epitope in the My-C and which does not have the cross-reactivity with respect to the myosin binding proteins of the skeletal muscle. Said hybridome cell line can be obtained by fusing myelome cells with spleen cells of a test animal, in particular a mouse, immunized against recombined My-C. The invention also relates to epitope specific antibodies produced by the hybridome cell lines and to the use thereof.

The invention relates to markers for acute myocardial infarction (AMI), particularly markers that may be used in the rapid and accurate diagnosis of AMI or reinfarction. A method of diagnosing cardiac injury comprising identifying an elevated concentration of cardiac myosin binding protein C (cMyBP-C) or a fragment thereof or myosin regulatory light chain 2 (MLC2) or a fragment thereof in a sample obtained from a subject.

The present disclosure provides a cDNA, protein sequence, and genomic structure of the human cardiac isoform of myosin light chain kinase (cMLCK), and describes mutations in the cMLCK gene that are associated with cardiac dysfunction. Methods are provided for identifying individuals who can harbor mutations in the cMLCK gene, or carry alleles that can predisposed them to cardiac dysfunction. Disclosed also is a significant role for cMLCK in modulating cardiac contractility. The cMLCK protein is shown herein to reduce the amplitude of stretch activation and increase the tension production, a property of muscle which has heretofore had an unknown role in cardiac contraction. Moreover, the cMLCK protein is shown to be regionally distributed in the heart, thereby having differential effects on contractility and stretch activation. Methods herein are provided to exploit this effect of cMLCK, to treat individuals who have or are prone to cardiac dysfunction. In addition, methods are provided to identify agents that modulate cMLCK activity, thereby having potential therapeutic importance in the treatment of cardiac dysfunction.