In a clinical trial that is probably one of the first of its kind, researchers from the laboratory of Marc Penn at the Summa Cardiovascular Institute in Akron, Ohio, activated the stem cells of heart failure patients by means of gene therapy.
Penn and his colleagues delivered a gene that encodes stromal-cell derived factor-1 or SDF-1. SDF-1 is a member of the chemokine family of signaling proteins, and chemokines are proteins that direct cells to get up and move somewhere. Thus, for stem cells, SDF-1 acts as a kind of “homing” signal.
In this unique study, Penn and his collaborators introduced SDF-1 into the heart in order to summon stem cells to the site of injury and enhance the body’s stem cell-based repair process. In a typical stem cell-based study, researchers extract and expand the number of cells, then deliver them back to the subject, but in this study, no stem cells were extracted. Instead they were summoned to the site of injury by SDF-1.
Marc Penn, professor of medicine at Northeast Ohio Medical University in Rootstown, Ohio and the director of research at Summa Cardiovascular Institute said of his clinical trial: “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.”
Previous research by Penn and colleagues has shown SDF-1 activates and recruits the body’s stem cells to sites of injury and this increases healing. Under normal conditions, SDF-1 is made after an injury but its effects are short-lived. For example, SDF-1 is naturally expressed after a heart attack but this augmented expression of SDF-1 only lasts only a week.
In the study, researchers attempted to re-establish and extend the time that SDF-1 could stimulate patients’ stem cells. The trial enrolled 17 NYHA Class III heart failure patients, with left ventricular ejection fractions less than 40% and an average time from heart attack of 7.3 years. Three escalating JVS-100 doses were evaluated: 5 mg (cohort 1), 15 mg (cohort 2) and 30 mg (cohort 3). The average age of the participants was 66 years old.
Researchers injected one of three doses of the SDF-1 gene (5mg, 15mg or 30mg) into the hearts of these patients, and monitored them for up to a year. Four months after treatment, they found:
1. Patients improved their average distance by 40 meters during a six-minute walking test.
2. Patients reported improved quality of life.
3. The heart’s pumping ability improved, particularly for those receiving the two highest doses of SDF-1 compared to the lowest dose.
4. No apparent side effects occurred with treatment.
According to Penn, “We found 50 percent of patients receiving the two highest doses still had positive effects one year after treatment with their heart failure classification improving by at least one level,” Penn said. “They still had evidence of damage, but they functioned better and were feeling better.”
Penn’s study suggests that our stem cells have the potential to induce healing without having to be taken out of the body. Penn said, “Our study also shows gene therapy has the potential to help people heal their own hearts.”
At the start of the study, participants didn’t have significant reversible heart damage, but lacked blood flow in the areas bordering their damaged heart tissue. The study’s results — consistent with other animal and laboratory studies of SDF-1 — suggest that SDF-1 gene injections can increase blood flow around an area of damaged tissue, which has been deemed irreversible by other testing.
In further research, Penn and his team are comparing results from heart failure patients receiving SDF-1 with patients who are not receiving SDF-1. If the trial goes well, the therapy could be widely available to heart failure patients within four to five years, Penn said.