May 29 2010
Bioheart, Inc., (OTC Bulletin Board: BHRT) announced today plans for establishing two Centers of Excellence in the Middle East to provide its cell therapy procedures to patients suffering from congestive heart failure (CHF) and peripheral arterial disease (PAD). Dr. Karl E. Groth, Chairman and CEO, and Peggy A. Farley, Chief Operating and Financial Officer, are now in that region holding discussions and performing site inspections.
Dr. Groth commented: "We feel that the Middle East region is a splendid second site for our Centers of Excellence. There is easy access to both of the sites that we are considering, Jordan and Turkey, from other countries in the Middle East as well as from Europe and South Asia." In light of site selection, Dr. Groth said: "Increasing economic wealth in the Middle East and North Africa has been accompanied by urbanization. Cardiovascular disease, a corollary to urban life, has been increasing rapidly and is now the region's leading cause of death, accounting for 25 to 45 percent of total deaths. Over the past few decades, daily per capita fat consumption has increased in most countries in the region, ranging from a 13.6 percent increase in the Sudan to a 143.3 percent increase in Saudi Arabia. Ischemic heart disease is the predominant cause of cardiovascular disease, with about three ischemic heart disease deaths for every stroke death. Also more prevalent in the Middle East than in the rest of the world, rheumatic heart disease remains a major cause of morbidity and mortality, but the number of hospitalizations related to this problem is declining rapidly. Cell technologies have not been used for treatment of rheumatic heart disease, but one can reason that they would be effective."
The company has commenced work in Jordan on its REGEN trial, a Phase I Clinical Trial to test genetically modified MyoCell® in patients suffering from Congestive Heart Failure (CHF). The first patient is expected to receive treatment in July.
Peggy Farley added: "The facilities and physicians in Jordan and Turkey are comparable to the best facilities and physicians in the United States. Once we introduce Bioheart's therapies into the Centers, patients with cardiac issues and limb ischemia will be able to access treatments that we have seen resolve those problems." Mentioning Bioheart's future plans, she went on to say: "Bioheart has plans for establishing a cell manufacturing facility in Jordan as well. Once there are a sufficient number of cases that are treated at our Middle East Centers of Excellence, it makes sense to have a second manufacturing site. Jordan's capabilities in laboratory medicine and its research into gene and cell solutions for medical problems are superb—superior to most in the world."
Bioheart's MyoCell® is a regenerative cell therapy that uses myoblasts, or muscle stem cells, that are grown from a patient's own muscle. MyoCell® has been tested successfully on patients in four clinical trials. The REGEN trial is designed to test the safety and effectiveness of a composition of muscle stem cells that have been gene-modified to induce a greater than usual release of the SDF-1 protein. The SDF-1 protein is a molecule in the human body that, after an injury, is naturally released by most tissues to attract stem cells. The stem cells assist with the healing process.
Unlike other tissues, the heart muscle does not release enough SDF-1 to attract the number of stem cells that would result in complete self-healing. As a result, scar tissue forms and impairs normal heart function.
Results from Bioheart's preclinical animal studies have shown that the genetically modified MyoCell® is far more effective than MyoCell® alone in accomplishing repair and tissue regeneration. With SDF-1, there is a release of additional therapeutic proteins to assist in the tissue repair process, resulting in a more expansive and quicker repair. Once that repair or regeneration has occurred, the patient's improved heart function permits the patient to return to a normal life style.
The REGEN trial is being funded by one of the company's institutional investors, the Ascent Medical Technology Funds, and the Philadelphia BioMed Product Development Centre, PSC, a preclinical and clinical research organization located in Amman, is responsible for the study. The trial is being conducted in Jordan because its clinical research capabilities and facilities rival those of the US and Europe. The country's leadership in medicine has made it a destination for patients from the Middle East, Europe, South Asia, and even the United States, for treatments that encompass the full range of complexity, including the most innovative procedures for ameliorating cardiovascular disease and cancers. The Jordanian government and medical community have commenced programs on cell and stem therapies, establishing four research centers to concentrate on these disorders.
Imad Alhaddad, MD, FACC, FACP and Co-Director of the Jordan Cardiovascular Centre, is Principal Investigator, leading the study. He is a pre-eminent interventional cardiologist. Previously, he was Director of Vascular Services at Johns Hopkins Hospital, and the author of many clinical studies, and an extensive number of publications. He is a member of the REGEN trial's Executive Committee also.
The treatment with MyoCell® involves taking a biopsy from the patient's leg muscle, transporting that biopsy to Bioheart's cell manufacturing facility, expanding the number of cells from the biopsy, and inducing the cells to regress to produce precursors to muscle cells called myoblasts. These cells know that they are muscle cells, but do not know which muscle. Once those precursor cells, or myoblasts, are present, they are segregated from the muscle cells and grown until they number over 1 billion cells. The myoblasts are then transported back to the patient's treatment centre. Some are then injected into the patient's heart with a needle tipped injection catheter. The treatment used in the REGEN trial involves genetically modifying myoblasts, utilizing Bioheart's proprietary process. The modified cells are injected in the same manner into the patient's heart. The modified myoblasts are created using an adenovirus vector or a non-viral vector. The myoblasts will release increased levels of the SDF-1 protein, which stimulates angiogenesis and regeneration of tissue.
A heart attack limits adequate blood flow to the heart. In response, the body naturally increases the level of SDF-1 protein in the heart but not enough to heal the damaged tissue. By modifying the myoblasts to express additional SDF-1, the SDF-1 protein levels present in the heart are multiplied exponentially.. The additional quantities of SDF-1 protein stimulate the recruitment of the patient's existing stem cells to the cell transplanted area. The recruited stem cells will assist in the tissue repair and blood vessel formation process. Preclinical animal studies showed a 54 percent improvement of heart function when the myoblasts were modified to increase SDF-1 protein prior to injection of myoblasts as compared to 27 percent for the animals treated using myoblasts without modification. The animals treated with a placebo showed a decline in function of 10 percent.
After completing the REGEN trial, the company plans to transition this second-generation product into its FDA approved Phase II/III MARVEL study. Bioheart plans to further study the modified myoblasts by treating a set of patients who are participating in the study and observing the differences in clinical and heart function among the modified group, those who are treated with MyoCell® alone, and a placebo.
Bioheart entered into its first Center of Excellence agreement with a leading treatment facilitator, Regenerative Medicine Institute of Tijuana, Mexico. Therapies for CHF and Peripheral Arterial Disease (PAD) patients have been made available at the Hospital Angeles Tijuana, a fully equipped state-of–the-art private specialties hospital.
Commenting further, Dr. Groth said: "Bioheart's mission is to see cardiovascular disease treated such that its victims can return to normal lives. Effective treatment with our therapies should not be confined to any geographic area of the world. These are global problems and there should be global solutions."
Warren Sherman, M.D., of Columbia University Medical Center's Stem Cell Research Institute, Chris O'Conner, M.D., and Tom Povsic, M.D., Ph.D., of Duke University's Clinical Research Institute, have, with Bioheart, established an Academic Advisory Committee to monitor these Centers of Excellence and gather data on the results seen by each Center. These results will, over time, become a compendium and form a nexus for future cell therapy research.
Bioheart's therapy for CHF and PAD utilizes stem cells derived from the patient's own fat (adipose tissue) through liposuction. Stem cells are then separated from the adipose tissue with the fully-automated TGI 1200 Cell Isolation System in about an hour. The recovered stem cells are injected into the heart with Bioheart's MyoCath catheter. No tissue pre-processing is required.
The MyoCath is a deflecting tip needle injection catheter that has a larger needle which is 25 gauge for better flow rates and less leakage than systems that are 27 gauge. This larger needle allows for thicker compositions to be injected which helps with cell retention in the heart. Also, the MyoCath needle has more fluoroscopic brightness than the normally used nitinol needle, enabling superior visualization during the procedure. Seeing the needle well during injections enables the physician who is operating the catheter to pinpoint targeted areas more precisely, thus improving safety.
Recent studies have identified adipose tissue as an alternate source of stem cells. The procedure for obtaining adipose derived stem cells from the patient is a relatively simple process and tolerated by most patients even immediately following a heart attack. Fat tissue can usually be found in abundance within the patient's own body and has a greater number of stem cells than bone marrow. The TGI 1200 system can isolate stem cells in about an hour, allowing for immediate clinical, point-of-care treatment after an event like a heart attack, which is important to the effectiveness of the treatment. In contrast, the procedure for obtaining stem cells from bone marrow can be painful and often yields a low volume of stem cells.
In addition to offering treatment for congestive heart failure, the TGI 1200 system will be used to obtain cells to treat lower limb ischemia using needle injections.
The final step for incorporating Bioheart therapies into its system will be making available MyoCell, Bioheart's muscle stem cell therapy for CHF. MyoCell is a clinical muscle-derived cell therapy designed to populate regions of scar tissue within a patient's heart with new living cells for the purpose of improving cardiac function in chronic heart failure patients.
Bioheart's Phase II European SEISMIC study demonstrated that 94% of patients treated with MyoCell, improved or did not worsen while only 6% deteriorated. Improvement or status quo in 6 minute walk distance was seen in 84% of treated patients, while only 16% saw a reduction. In those patients treated with a placebo, 42% saw deterioration in their Heart Failure class and 69% saw a reduction in distance with their 6 minute walk. Bioheart's MARVEL Trial 1 saw commensurate results. The MARVEL trial is a Phase II/III study.
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