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Heart Damage Repaired By Reprogramming Resident Fibroblasts into Functioning Heart Cells
Date:5/29/2012

LAGUNA HILLS, Calif., May 29, 2012 /PRNewswire/ -- LoneStar Heart Inc., today 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 on-line May 13th 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 Dr. 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 Dr. 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.

About LoneStar Heart, Inc.
LoneStar Heart, Inc. is developing cardiac restorative therapies for patients with heart failure that stimulate the heart's ability to repair itself. Based on its integrated cardiomechanical and biomolecular technologies, the privately held company is advancing a broad portfolio of products to restore the failing heart's structure and function in collaboration with the Texas Heart Institute, UT Southwestern, and a global network of leading clinicians. These products include Algisyl-LVR™, cardiac stem-cell modulators, and cellular and genetic therapies delivered as stand-alone treatments, or in combination with the company's biopolymer matrix system.

LoneStar Heart's lead product, Algisyl-LVR, is a single-use, self-gelling biopolymer implant­ed into the heart's left ventricle during surgery. Providing internal tissue support, Algisyl-LVR is aimed at preventing the progression of heart failure and restoring the heart's normal structure and function with a significant improvement in the patient's quality of life. Classified as a medical device, the product is undergoing a randomized controlled clinical study (AUGMENT-HF) in Europe to evaluate its safety and efficacy in patients with advanced heart failure.

About UT Southwestern Medical Center
UT Southwestern Medical Center, one of the premier medical centers in the nation, integrates pioneering biomedical research with exceptional clinical care and education. Its faculty has many distinguished members, including five who have been awarded Nobel Prizes since 1985. Numbering more than 2,600, the faculty is responsible for groundbreaking medical advances and is committed to quickly translating science-driven research to new clinical treat­ments. UT Southwestern physicians provide medical care in 40 specialties to more than 100,000 hospitalized patients, and oversee nearly 2 million outpatient visits a year.

Physicians care for patients in the Dallas-based UT Southwestern Medical Center; in Parkland Health & Hospital System, which is staffed primarily by UT Southwestern physicians; and in its affiliated hospitals, Children's Medical Center Dallas, Texas Scottish Rite Hospital for Children and the VA North Texas Health Care System. UT Southwestern programs are offered in Waco, Wichita Falls, Plano/Frisco and Fort Worth. Three degree-granting institutions – UT Southwestern Medical School, UT Southwestern Graduate School of Biomedical Sciences and UT Southwestern School of Health Professions – train nearly 4,600 students, residents and fellows each year. UT Southwestern researchers undertake more than 3,500 research projects annually, totaling more than $417 million.

Dr. Olson holds the Pogue Distinguished Chair in Research on Cardiac Birth Defects, the Robert A. Welch Distinguished Chair in Science, and the Annie and Willie Nelson Professorship in Stem Cell Research at UT Southwestern.


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SOURCE LoneStar Heart Inc.
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