Beyond Algisyl® and the MyoTEC™ System, LoneStar Heart’s research programs target native cardiac muscle regeneration. The combination of Algisyl® and similar hydrogels with additional peptides, small molecules, or biologics are expected to deliver the benefits of the hydrogel with the pharmacological benefits of an active agent.
Recent studies show that adult cardiomyocytes, the muscle cells of the heart, have a low turnover rate and are consequently capable of muscle regeneration. Regrettably, this regenerative capacity is insufficient when the heart is damaged by chronic disease, old age, or acute events such as a myocardial infarct. In these injuries, cardiac fibroblasts generate scar material that limits further cell damage but does not contribute to the heart’s function thus leaving fewer muscle cells with more work to compensate for the damage. The Company’s collaborators at University of Texas Southwestern Medical Center (UTSW) have made significant progress in understanding the molecular basis of both cardiogenesis and injury response. Resulting from this research, they have identified novel therapeutic approaches licensed to the company that modify injury response to contribute to muscle regeneration.
LoneStar Heart has acquired a family of patented small molecules that interact with cardiac progenitor cells to enhance native stem cell-mediated repair. In rodents, these molecules have been shown to promote functional recovery after myocardial infarction (MI). Mechanistic studies determined that the molecules activated a relevant G protein-coupled receptor expressed by cells that are accumulated subepicardially. This receptor has now been shown to regulate myocardial cellular responses to tissue acidosis.
LoneStar Heart has also acquired two biologic programs to cardiac muscle regeneration. The first one utilizes a gene therapy approach whereby four transcription factors are employed to reprogram cardiac fibroblasts into cardiomyocytes. The resulting cells display contractility and calcium handling similar to native cardiomyocytes indicating their functionality. Additionally, the Company has a US-patented product consisting of the secreted proteins of stem cells cultured under hypoxic conditions. Rather than using the stem cells directly, the approach consists of injecting the cocktail of growth factors, chemokines, and other proteins produced by the stem cells ex-vivo to the heart to generate an angiogenic and myogenic response. This product has clear practical advantages over conventional cell therapies and has shown potential in a large animal model.
The company’s early stage programs (small molecules and biologics) hold significant longer term potential. LoneStar Heart is prepared to engage in partnership discussions to form development alliances.