Gene therapy improved outcomes in symptomatic HF

In a first-of-its-kind study, researchers activated HF patients’ stem cells with gene therapy to improve their symptoms, heart function and quality of life.

The data, published in Circulation Research, suggest that non-viral stromal cell-derived factor-1 (SDF-1) gene therapy may have a positive effect in this patient population. SDF-1 is a naturally occurring protein that guides the movement of other cells. Previous research by Marc S. Penn, MD, PhD, and colleagues has shown that SDF-1 activates and recruits the body’s stem cells, which leads to healing of damaged tissue, according to a press release.

Stem cell ‘homing’ signal

The aim of the new study was to re-establish and extend the time that SDF-1 could stimulate stem cells. This study is unique because the researchers introduced a “homing” factor to draw stem cells to the site of injury and enhance the body’s stem cell-based repair process, according to the press release.

“We believe stem cells are always trying to repair tissue, but they don’t do it well — not because we lack stem cells but, rather, the signals that regulate our stem cells are impaired,” said Penn, director of research at Summa Cardiovascular Institute in Akron, Ohio, and professor of medicine at Northeast Ohio Medical University.

The phase 1, open-label, dose-escalation study included 17 patients. All had ischemic cardiomyopathy, NYHA Class III HF and ejection fraction ≤40% who were on stable medical therapy. The mean age of the patients was 66 years.

Via endomyocardial injection, researchers administered 5 mg, 15 mg or 30 mg of the SDF-1 gene therapy (JVS-100, Juventas Therapeutics Inc.) and followed patients for up to 1 year.

Four months after treatment, all dose groups experienced improvements in 6-minute walk test distance, quality of life and NYHA Class. Patients in the higher-dose groups demonstrated the greatest improvements over baseline: a 31-m to 41-m improvement in the 6-minute walk test and 16- to 24-point improvement in quality of life.

Improvements were maintained at 1 year.

“We found 50% of patients receiving the two highest doses still had positive effects 1 year after treatment with their HF classification improving by at least one level,” Penn said. “They still had evidence of damage, but they functioned better and were feeling better.”

No apparent adverse effects occurred with the treatment. According to the study findings, the majority of serious adverse events were related to underlying disease, and no serious adverse events were related to treatment.

Future directions

These SDF-1 phase 1 HF study findings indicate that patients’ stem cells have the potential to induce healing without having to be removed from the body. The results are consistent with other animal and laboratory studies of SDF-1, according to the researchers.

Research is under way to compare results from HF patients administered SDF-1 with patients who are not administered gene therapy. If the trial goes well, this therapy could potentially be widely available to HF patients within 4 to 5 years, Penn said.

For more information:

Penn MS. Circ Res. 2013;doi:10.1161/CIRCRESAHA.111.300440.

Disclosure: The study was funded by Juventas Therapeutics Inc. Penn is named as an inventor on patent applications filed by the Cleveland Clinic for the use of SDF-1 to treat CVDs that have been licensed by Juventas Therapeutics; as such, he is eligible for royalties from and equity in Juventas Therapeutics. Penn is also founder and chief medical officer of Juventas Therapeutics and is a paid consultant.