Navigation Links
Gene therapy reprograms scar tissue in damaged hearts into healthy heart muscle

NEW YORK (Jan. 4, 2013) -- A cocktail of three specific genes can reprogram cells in the scars caused by heart attacks into functioning muscle cells, and the addition of a gene that stimulates the growth of blood vessels enhances that effect, said researchers from Weill Cornell Medical College, Baylor College of Medicine and Stony Brook University Medical Center in a report that appears online in the Journal of the American Heart Association.

"The idea of reprogramming scar tissue in the heart into functioning heart muscle was exciting," said Dr. Todd K. Rosengart, chair of the Michael E. DeBakey Department of Surgery at BCM and the report's corresponding author. "The theory is that if you have a big heart attack, your doctor can just inject these three genes into the scar tissue during surgery and change it back into heart muscle. However, in these animal studies, we found that even the effect is enhanced when combined with the VEGF gene."

"This experiment is a proof of principle," said Dr. Ronald G. Crystal, chairman and professor of genetic medicine at Weill Cornell Medical College and a pioneer in gene therapy, who played an important role in the research. "Now we need to go further to understand the activity of these genes and determine if they are effective in even larger hearts."

During a heart attack, blood supply is cut off to the heart, resulting in the death of heart muscle. The damage leaves behind a scar and a much weakened heart. Eventually, most people who have had serious heart attacks will develop heart failure.

Changing the scar into heart muscle would strengthen the heart. To accomplish this, during surgery, Rosengart and his colleagues transferred three forms of the vascular endothelial growth factor (VEGF) gene that enhances blood vessel growth or an inactive material (both attached to a gene vector) into the hearts of rats. Three weeks later, the rats received either Gata4, Mef 2c and Tbx5 (the cocktail of transcription factor genes called GMT) or an inactive material. (A transcription factor binds to specific DNA sequences and starts the process that translates the genetic information into a protein.)

The GMT genes alone reduced the amount of scar tissue by half compared to animals that did not receive the genes, and there were more heart muscle cells in the animals that were treated with GMT. The hearts of animals that received GMT alone also worked better as defined by ejection fraction than those who had not received genes. (Ejection fraction refers to the percentage of blood that is pumped out of a filled ventricle or pumping chamber of the heart.)

The hearts of the animals that had received both the GMT and the VEGF gene transfers had an ejection fraction four times greater than that of the animals that had received only the GMT transfer.

Rosengart emphasizes that more work needs to be completed to show that the effect of the VEGF is real, but it has real promise as part of a new treatment for heart attack that would minimize heart damage.

"We have shown both that GMT can effect change that enhances the activity of the heart and that the VEGF gene is effective in improving heart function even more," said Dr. Crystal.

The idea started with the notion of induced pluripotent stem cells reprograming mature specialized cells into stem cells that are immature and can differentiate into different specific cells needed in the body. Dr. Shinya Yamanaka and Sir John B. Gurdon received the Nobel Prize in Medicine and Physiology for their work toward this goal this year.

However, use of induced pluripotent stem cells has the potential to cause tumors. To get around that, researchers in Dallas and San Francisco used the GMT cocktail to reprogram the scar cells into cardiomyocytes (cells that become heart muscle) in the living animals.

Now Rosengart and his colleagues have gone a step farther encouraging the production of new blood vessels to provide circulation to the new cells.


Contact: Lauren Woods
Weill Cornell Medical College

Related biology news :

1. New whole plant therapy shows promise as an effective and economical treatment for malaria
2. Transplanted genetically-modified adipose cells offer potential therapy for liver diseases
3. Serendipity points to new potential target and therapy for melanoma
4. MicroRNAs present exciting opportunities for cancer therapy and diagnosis
5. Alzheimers disease: Cutting off immune response promises new approach to therapy
6. Potential gene therapy approach to sickle cell disease highlighted at ASH
7. Predictors of cancer disease progression improve patient selection for metastasis-directed therapy
8. Leukemia patients remain in remission more than 2 years after engineered T cell therapy
9. Another muscular dystrophy mystery solved; MU scientists inch closer to a therapy for patients
10. New technique to deliver stem cell therapy may help damaged eyes regain their sight
11. Research shows immune system response is detrimental to novel brain cancer therapy
Post Your Comments:
(Date:11/2/2015)... 2015  SRI International has been awarded a contract ... services to the National Cancer Institute (NCI) PREVENT Cancer ... expertise, modern testing and support facilities, and analytical instrumentation ... toxicology studies to evaluate potential cancer prevention drugs. ... Cancer Drug Development Program is an NCI-supported pipeline to ...
(Date:10/29/2015)... Va. , Oct. 29, 2015 Daon, ... today that it has released a new version of ... customers in North America have ... IdentityX v4.0 also includes a FIDO UAF certified ... are already preparing to activate FIDO features. These customers ...
(Date:10/29/2015)... 29, 2015 NXTD ) ... focused on the growing mobile commerce market and ... StackCommerce, a leading marketplace to discover and buy ... smart wallet on StackSocial for this holiday season. ... the "Company"), a biometric authentication company focused on ...
Breaking Biology News(10 mins):
(Date:11/25/2015)... , November 26, 2015 ... Biobanking Market 2016 - 2020 report analyzes that ... integrity and quality in long-term samples, minimizing manual ... cost-effectiveness. Automation minimizes manual errors such as mislabeling ... efficiency. Further, it plays a vital role in ...
(Date:11/25/2015)... ANGELES and HOLLISTON, Mass. ... Technology, Inc. (Nasdaq: HART ), a biotechnology company ... that CEO Jim McGorry will present at ... December 1, 2015 at 2:30 p.m. PT. The presentation ... below) for 30 days. Management will also be available ...
(Date:11/25/2015)... DIEGO , Nov. 25, 2015 Orexigen® ... management will participate in a fireside chat discussion at ... New York . The discussion is scheduled ... .  A replay will be ... Media Contact:McDavid Stilwell  , Julie NormartVP, Corporate Communications ...
(Date:11/24/2015)... , ... November 24, 2015 , ... The United States ... of the 2016 USGA Green Section Award. Presented annually since 1961, the USGA Green ... or her work with turfgrass. , Clarke, of Iselin, N.J., is an ...
Breaking Biology Technology: