June 1, 2012 — LoneStar Heart Inc. announced the advancement of a new therapeutic strategy aimed at genetic reprogramming of cardiac fibroblasts into functioning heart muscle cells to treat damage following a heart attack and other forms of heart disease. The announcement follows a study conducted by researchers at the University of Texas Southwestern Medical Center (UT Southwestern), published in the online May 13 issue of the journal Nature, demonstrating feasibility of the approach. The company has acquired exclusive worldwide rights to the new technology.
The adult human heart has almost no regenerative capacity. Instead of rebuilding muscle tissue after a heart attack, or myocardial infarction, the injured human heart forms fibrous, non-contractile scar tissue lacking muscle or blood vessels. Fibroblasts account for a majority of cells in the heart and are activated following injury to form this fibrotic scar tissue. Fibrosis impedes regeneration of cardiac muscle cells, and contributes to loss of contractile function, ultimately leading to heart failure and death. Therapeutic strategies to promote new muscle formation, while limiting fibrosis, represent an attractive approach for heart repair.
As reported in Nature, Eric N. Olson, Ph.D., and colleagues from UT Southwestern show that four gene-regulatory proteins — GATA4, HAND2, MEF2C, and TBX5 (GHMT) — can convert cardiac fibroblasts into beating cardiac-like muscle cells. Introduction of these proteins into proliferating fibroblasts in mice reprograms them into functional cardiac-like myocytes, improving cardiac function and reducing fibrosis and adverse remodeling of the heart following myocardial infarction. Using cell lineage-tracing techniques, the investigators conclude that newly formed cardiac-like muscle cells in GHMT-treated hearts arose from pre-existing cardiac fibroblasts. Cardiac imaging studies confirmed the new technique promoted a dramatic increase in cardiac function that was sustained for at least three months following myocardial infarction.
"These studies establish proof-of-concept for in vivo cellular reprogramming as a new approach for heart repair," said Olson, professor and chair of molecular biology at UT Southwestern, and a co-founder of LoneStar Heart. "However, much work remains to be done to determine if this strategy might eventually be effective in humans. We are working hard toward that goal."
The new reprogramming strategy may provide a novel means of improving cardiac function following injury, bypassing many of the obstacles associated with cellular transplantation. Prior work by Olson's group and others has shown that GHMT proteins fulfill similar roles in cardiac gene regulation in a wide range of organisms, including humans, highlighting the potential of these proteins to augment function of the injured human heart. While cellular replacement strategies via the introduction of stem cells or other cell types into injured hearts have shown promise, there have been numerous technical and biological hurdles associated with such approaches.
For more information: www.lonestarheartinc.com
December 20, 2023 
