Gene Therapy Increases Stem Cell Recruitment to Heart and Improves Heart Function


Data from a Phase 2 clinical trial is creating quite a stir in cardiology circles. According to the findings of this study, the single administration of a gene on a non-viral-derived plasmid improves cardiac structure, function, serum biomarkers and clinical status in patients with severe ischemic heart failure one year after treatment.

The results from the final 12-months of the Phase 2 STOP-HF clinical trial for the JVS-100 treatment were presented at the European Society of Cardiology – Heart Failure 2015 meeting by the developer of this technology: Juventas Therapeutics Inc. The founder of Juventas, Marc Penn, M.D., Ph.D., FACC, is also the medical officer and director of Cardiovascular Research and Cardiovascular Medicine Fellowship at Summa Health in Akron, Ohio. Dr. Penn presented the results of this randomized, double-blind, placebo-controlled STOP-HF trial, which included treatments on 93 patients at 16 different clinical centers in the United States.

“The results from STOP-HF demonstrate that a single administration of 30 mg of JVS-100 has the potential to improve cardiac function, structure, serum biomarkers and clinical status in a population with advanced chronic heart failure who are symptomatic and present with poor cardiac function,” stated Dr. Penn. “These findings combined with our deep understanding of SDF-1 biology will guide future clinical trials in which we plan to prospectively study the patient population that demonstrated the most pronounced response to JVS-100. In addition, we will further our understanding of JVS-100 by determining if a second administration of drug may enhance benefits beyond those we observed with a single administration.”

These study. some patients received a 30 mg dose of JVS-100 while others received a placebo.  Patients who received JVS-100 showed definite improvements 12 months after treatment.  The cardiac function and heart structure of the patients who received JVS-100 were far better than those who had received the placebo.  JVS-100-treated patients showed a changed in left ventricle ejection fraction of 3.5% relative to placebo, and left ventricular end-systolic volume of 8.5 ml over placebo.  When patients were asked to walk for six minutes, the JVS-100-treated patients were better than patients who had received the placebo.  Likewise, when patients were given the Minnesota Living with Heart Failure Questionnaire, the JVS-100-treat patients had a better score than those who had received the placebo.  Also, there were no unanticipated serious adverse events related to the drug reported for the study.

JVS-100 is a non-viral DNA plasmid gene therapy. Plasmids are small circles of DNA that are relatively easy to manipulate, grow and propagate in bacterial cells. In the case of the JV-100 treatment, the plasmid encodes a protein called stromal cell-derived factor 1 (SDF-1). SDF-1 is a naturally occurring signaling protein that recruits stem cells from bone marrow to the site of SDF-1 expression. SDF-1, therefore, acts as a stem cell recruitment factor that summons stem cells to the places where they are needed.

When JV-100 is delivered directly to a site of tissue injury, it induces the expression of SDF-1 protein into the local environment for a period of approximately three weeks. SDF-1 secretion creates a homing signal that recruits the body’s own stem cells to the site of injury to induce tissue repair and regeneration.

Juventas is developing JVS-100 into a treatment of advanced chronic cardiovascular disease, including heart failure and late stage peripheral artery disease.

These improvements in heart function are relatively modest.  Therefore, it is difficult to get too excited about these results.  Also, Alexey Bersenev, a umbilical cord stem cell researcher, noted that the primary end points (or goalposts) for this trial were not met, and that makes this an unsuccessful trial.  Despite this bad news, JV-100 does seem to be safe, and the theory seems sound, even if the results are more than a little underwhelming.

A New Way to Treat Kidney Disease and Heart Failure


St. Michael’s Hospital in Toronto, Ontario is the site of new research that uses bone marrow stem cells to treat chronic kidney disease and heart failure in rats.

Darren Yuen and Richard Gilbert of St. Michael’s Hospital were the first to show in 2010 that enriched stem cells improved heart and kidney functions in rats afflicted with both diseases. Their work generated concerns about the side effects of returning such stem cells to the body.

Since 2010, Yuen and Gilbert have found that enriched bone marrow stem cells secrete stromal cell–derived factor-1α (SDF-1α), a chemokine that is made by ischemic tissue but is rapidly degraded by dipeptidyl peptidase-4 (DPP-4), in culture dishes.  Injection of SDF-1α into rats has many of the same positive effects as when the stem cells themselves are injected into rats.  Even more remarkably, if a drug that inhibits the enzyme DPP-4 is given (sitagliptin) produced many improvements as well.

“We’ve shown that we can use these ‘hormones’ to replicate the beneficial effects of the stem cells in treating animals with chronic kidney disease and heart failure,” said Yuen, who practices as a nephrologist. “In our view, this is a significant advance for stem cell therapies because it gets around having to inject stem cells.”

Yuen said that they do not yet know what kind of hormone the cells are secreting, but identifying the hormone would be the first step toward the goal of developing a synthetic drug.

Chronic kidney disease (CKD) is much more prevalent than was once believed, with recent estimates suggesting that up to five percent of the Canadian population may be affected with this condition.

The number of people with CKD and end-stage renal failure is expected to rise as the population ages and more people develop Type 2 diabetes. People with kidney disease often develop heart disease, and many of them die from heart failure rather than kidney failure.

ATHENA Trial Tests Fat-Derived Stem Cells as a Treatment for Heart Failure


The FDA-approved ATHENA trial is the brainchild of stem cell researchers at the Texas Heart Institute at St. Luke’s Episcopal Hospital. The ATHENA trial is the first trial in the United States to examine the efficacy of adipose-derived regenerative cells or ADRCs as a treatment for a severe form of heart failure.

To harvest ADRCs, Texas Heart Institute researchers used a technique that was developed by Cytori Therapeutics, which is a biotechnology company that specializes in cell-based regenerative therapies. Previous clinical trials in Europe strongly suggest that such ADR-based therapies are quite safe and feasible. To date, physicians are the Texas Heart Institute have treated six patients as a part of the ATHENA trial.

athena_process_illustration_500x369.jpg

James Willerson, the president and medical director of the Texas Heart Institute, is the principal investigator in the ATHENA trial. Willerson said, “We have found that body fat tissue is a valuable source of regenerative stem cells that are relatively easy to access. We have high hopes for the therapeutic promise of this research and believe that it will lead quickly to larger trials.”

The subjects for the ATHENA trial are patients who suffer from chronic heart failure due to coronary heart disease. Coronary heart disease results from blockage of the coronary vessels and feed the heart muscle and limits the oxygen supply to the heart muscle, and consequently, the pumping activity of the heart muscle. Data from the American Heart Association reveals that there are about 5.1 million Americans who currently live with heart failure, and in many cases, the only viable treatment is a left ventricular assist device (LVAD) or a heart transplant. Unfortunately, there are only about 2,200 heart transplants a year due to a severe shortage of organs.

Coronary artery disease

Patients who are enrolled in the ATHENA trials are randomized and some will receive a placebo treatment and others will receive the experimental treatment. All patients will undergo liposuction in order to remove adipose or fat tissue. Processing of the fat tissue isolates the ADRCs, and the experimental patients will have these cells injected directly into their heart muscle, but the placebo patients will receive injections of culture medium or saline that contains no cells. ATHENA will measure several data endpoints that include objective measures of heart function, exercise capacity, and questionnaires that assess the symptoms and health-related quality-of-life.

The US trial will enroll a total of 45 patients at several centers around the country and these centers include the Texas Heart Institute, Minneapolis Heart Institute, Scripps Green Hospital in San Diego, CA, the University of Florida at Gainesville, and Cardiology P.C. in Birmingham. Patients are being enrolled.

Healthline has recently compiled the statistics on heart disease in an impressive and colorful manner at this link.