Florida Atlantic University received U.S. patent no. 10/822,496, “Promoting Cardiac Cell Differentiation,” based on an invention which induces and restores cardiac muscle function.
The invention was discovered by FAU researcher and vice president for research, Dr. Larry F. Lemanski and his postdoctoral fellow, Dr. Chi Zhang. Their research has focused on understanding the mechanisms that regulate myocardial (heart muscle mass) cell differentiation and myofibrillogenesis (the process by which proteins in the heart are changed into heart muscle cells) in the developing heart. From their findings, these researchers hope to repair myocardial deficiencies in the human heart which are caused by either congenital heart defects or heart attacks. embryonic heart.jpg)
A. Normal axolotl (salamander) embryonic heart cultured in a solution and stained for a protein called tropomyosin. Tropomyosin is a component of heart muscle myofibrils. Substantial tropomyosin staining is evident here in the myofibrils (the functional contractile units in cardiac muscle). B. Mutant axolotl embryonic heart cultured in a solution and stained for tropomyosin. There is very little staining for tropomyosin as compared to a normal heart showing a lack of muscle organization in mutant hearts. C. Mutant embryonic heart cultured in a solution containing normal Myofibril Inducing RNA or "MIR." Tropomyosin is abundant in these hearts which shows organization of myofibrils due to MIR treatment. MIR was able to rescue the mutant heart causing the formation of myofibrils and the initiation of beating.
Lemanski, Zhang and their colleagues at FAU have been looking at the cellular, molecular and genetic signals that affect heart cell differentiation and regulation of the synthesis of contractile proteins within cardiac muscle cells that allows cells to contract. Identifying the biological factors that induce this differentiation would be a major step forward in the development of therapies.
“When an individual has a heart attack with a significant region of the heart muscle damaged, recovery to pre-heart attack levels are rarely achieved,” said Lemanski. “Strategies to regenerate damaged cardiac tissue could be significant in the treatment of cardiovascular disease.”
Adult heart muscle cells lack the ability to regenerate following injury because of terminal differentiation. The number of heart cells is determined at birth and once damaged cannot repair themselves. Furthermore, many congenital abnormalities are thought to be caused by improper signaling between cells and tissues as a result of abnormal genes.
Observing cardiac mutant Mexican axolotls (salamanders), these researchers identified a major protein that was deficient in these axolotl hearts which prevented the organization of myofibrils (contractile machinery) and the ability to beat. Using these findings, Lemanski, Zhang and their colleagues were able to show that this mutant defect could be rescued by treatment with specific and unique RNA (ribonucleic acid) derived from the anterior endoderm (gut) of normal animal model embryos. They cloned the gene for this specific RNA, synthesizing a “bioactive” RNA that is capable of rescuing mutant hearts by promoting the development and differentiation of contractile cardiac muscle cells from non-contractile, pre-cardiac, non-muscle cells.
Lemanski termed this discovery as “myofibrillogenesis inducing RNA” or MIR. Additional studies have shown that humans have a similar, most likely identical, mechanism as the axolotls, for the formation of functional contracting heart muscle cells. It may also be possible to produce new functional cardiac muscle tissue in areas of human hearts that require these cells and tissues for restoration of normal function.
“The issuance of this patent marks a tremendous achievement for Drs. Lemanski and Zhang as well as FAU, especially at a time when the United States Patent and Trademark Office (USPTO) continues to implement a tougher examination process,” said Stephen Nappi, director of technology transfer and assistant vice president for research at FAU. “To continue to build upon this momentum, we will aggressively seek to identify and recruit the right company to help us bring this important invention to patients with cardiovascular disease.”
Taken into the clinical setting, a human version of this MIR may allow patients who have suffered from heart attacks and have impaired physical activities due to scar tissue in their hearts to have those scarred areas replaced with new cardiac muscle. This treatment would therefore enable them to return to pre-heart attack activity levels. In addition, children who are born with congenital heart defects could have those defective areas of their hearts repaired without a series of invasive surgical operations.
According to the American Heart Association, cardiovascular diseases (CVD) rank as America’s number one killer, claiming the lives of over 36 percent of the more than 2.4 million who die each year in the United States. Furthermore, 79.4 million people in the U.S. have some form of CVD. These include diseases of the heart, stroke, high blood pressure, congestive heart failure, congenital cardiovascular defects, hardening of the arteries and other diseases related to the circulatory system.
Lemanski also serves as president and chair of the FAU Research Corporation and is a professor of biomedical sciences in the Charles E. Schmidt College of Biomedical Science and a professor of biology and chemistry in the Charles E. Schmidt College of Science at FAU. He is a prolific researcher in the field of cellular, molecular and developmental biology and has numerous research publications, book chapters and proceedings to this credit, as well as many presentations at national and international conferences.
Source: Florida Atlantic University