How can you mend a broken heart? Grow new heart tissue. Bioheart (Sunrise, Florida) is launching the very first clinical trial ever to test a combination gene and stem cell therapy for congestive heart failure (CHF), a condition for which there is no cure other than a transplant.

Bioheart has reported that the FDA cleared a phase I trial for MyoCell SDF-1 (Stromal Derived Factor-1) to treat CHF.

"In our animal studies, we saw double the improvement that we did in the first-generation MyoCell products," Kristin Comella, VP of R&D and corporate development, told Medical Device Daily.

The 15-patient REGEN trial will be a multicenter, randomized, dose escalation study to assess the safety and cardiovascular effects of the implantation of MyoCell SDF-1 in CHF patients post myocardial infarction. Those patients will then be followed for 12 months.

MyoCell SDF-1 is a composition of myogenic stem cells derived from a patient's own thigh muscle that has been modified to over-express the SDF-1 protein. Using a needle-tipped catheter inserted into the groin of a patient who is suffering from CHF, the cells are injected into the scar tissue that has formed in the patient's heart.

"It's almost certain that you develop scar tissue with CHF because if there is no longer blood flow to the heart and no oxygen, the damaged muscle leads to scar tissue," Comella said.

In addition to growing new heart tissue, Comella said investigators hope that the therapy will also lead to reverse remodeling (shrinkage of the heart) because most people with CHF generally developed enlarged hearts as a result of CHF. They would also like to improve quality of life and extend life, but none of these issues are endpoints of this phase I trial.

The goal of MyoCell SDF-1 is to grow new contractile muscle within the scar tissue that will have the ability to release additional beneficial proteins to assist in the tissue repair process and improve the patient's heart function, exercise capacity and quality of life.

Comella said, "With this second-generation product, we transduce the cells using a viral vector to over-express SDF 1, which is the protein that assists in the angiogenesis process to form new vessels. It also acts as a homing signal to attract more stem cells to the area."

Last year the company reported that the first-generation product, MyoCell myoblast clinical cell therapy, is a safe and potentially effective alternative treatment to standard medical therapy alone for improving heart function among patients with previously implanted cardiac devices who are experiencing CHF.

The findings from the SEISMIC trial, a 40-patient, randomized, multicenter, controlled, phase II-a study conducted in Europe, evaluated MyoCell myoblast clinical cell therapy delivered via the MyoCath, endoventricular needle-injection catheter in patients previously fitted with implanted cardiac defibrillators, receiving standard medical therapy and who are experiencing congestive heart failure (Medical Device Daily, April 3, 2008).

Preclinical studies of this second-generation product, MyoCell SDF-1, showed that it provided a 54% improvement of heart function compared to 27% for the original MyoCell composition while the placebo control treated animals declined by 10%. The preclinical studies also demonstrated that MyoCell SDF-1 can enhance blood vessel formation in damaged hearts.

"We are happy to be able to begin the REGEN trial to test this promising product candidate in heart failure patients after completing very successful preclinical testing," said Howard Leonhardt, Bioheart's chairman/CEO. "To our knowledge, this will be the first clinical trial ever to test a combination gene and stem cell therapy for cardiovascular disease."

The U.S. trial is expected to begin this year.

After completing the REGEN safety protocol with one-month follow-up, the company plans to transition the second-generation product into its FDA-authorized phase II/III MARVEL study.

MyoCell SDF-1 is substantially similar to the original MyoCell composition that has been active in clinical trials since early 2001 at more than 50 centers worldwide.

The patents Bioheart has acquired covering the myogenic cells and SDF-1 compositions and methods are expected to provide intellectual property protection until 2023.

Bioheart is working to keep the funding pipeline open to continue the studies, despite some difficulties.

Last year, Bioheart made headlines as the only biotech firm to raise money through an initial public offering on the U.S. markets, though it raised only $5.8 million through the sale of 1.1 million shares at $5.25 each (MDD, Feb. 22, 2008). But in March, the company received notification from Nasdaq that its listing was discontinued after it failed to comply with certain requirements, including the market value of its common stock and either minimum stockholders' equity or net income from continuing operations of $500,000 in the most recently completed fiscal year or two of its last three most recently completed fiscal years (MDD, March 3, 2009).

Bioheart is in the midst of a fundraising. Earlier this month, it reported that commencing on Oct. 1, 2008, and through July 7, 2009, Bioheart received proceeds in the amount of $2.85 million from the placement of restricted common stock and warrants under its current offering under Regulation D.

That term has been extended through October 2009.