All concepts, explanations, trials, and studies have been re-written in plain English and may contain errors. I am not a doctor ----------------------------------------------------------- NOTE: You can make the print bigger with the font button on your browser! (It's usually a big "A") ----------------------------------------------------------- VEGF Gene Therapy for Heart Failure Reaching Phase 3 Trials By Martha Kerr (Reuters Health) November 21, 2002 - Gene therapy, using Vascular Endothelial Growth Factor 121 (AdVEGF121, Biobypass, GenVec), causes regrowth of blood vessels and improves exercise tolerance in patients with end-stage heart disease who are not candidates for surgery. Dr. Duncan John Stewart presented phase 2 results of 71 "no option" patients with end-stage CHF randomized to either maximum drug therapy or VEGF therapy. Patients in the VEGF group got as many as 30 injections of VEGF directly into all regions of the left ventricle through a small incision in the chest. At 12 weeks, there was no difference in exercise tolerance between the groups. However, at 26 weeks, there was an increase of more than a minute in exercise tolerance in the VEGF group. The VEGF group also took longer during exercise to show a change in ST segment. Time to angina with exercise was more than 3 minutes in the VEGF group, longer than in controls. Heart class improvement was also noticeable in the VEGF group, while there was none in controls. Quality of life measures were all better in the VEGF group than controls. There were 10 major adverse events in the VEGF group compared to 11 in controls. There were 2 deaths in the VEGF group compared with one in the control group. Both deaths in the study group were related to the chest incision surgical procedure, rather than the actual VEGF therapy. Phase 2 studies are planned, but Dr. Stewart says the team will change their method of VEGF delivery to catheter for safety. Dr. Stewart said, "It takes some time for blood vessels to form, but [VEGF therapy] appears to have a durable effect, which appears to be lasting even longer than the follow-up in this study." ======================================== Myoblast and Bone Marrow Stem Cell Trials Near Phase 2 By Martha Kerr (Reuters Health) November 18, 2002 - Results of some early trials suggest that cell transplant, using either skeletal muscle cells or bone marrow stem cells, is safe for regenerating heart function in areas damaged by heart attack. Dr. Nabil Dib reports that his team has safely transplanted muscle cells into ischemic areas of the heart in 16 heart attack patients who were having either bypass surgery (11 patients) or LVAD implant (5 patients). The researchers took a skeletal muscle biopsy of the patients' main leg muscle (front thigh), separated the muscle cells, and grew the cell lines for 2 to 3 weeks. The cells were then injected back into damaged areas of the patients' hearts. Before surgery, patients had average left LVEF of 23%. At 12 weeks, LVEF increased to an average of 36%. There were no cases of deterioration in EF. There was one death in the group that was related to LVAD infection. This phase one safety trial has shown safety so Dr. Dib's team is moving into phase 2 trials. A British team is using a similar approach, using bone marrow stem cells. Dr. Manuel Galinanes reported results of his phase one trial of 14 heart attack patients who received bone marrow obtained through sternal aspirate. The stem cells were then injected into the hearts' damaged areas. Dr. Galinanes reported that heart wall motion has improved in 10 of the 14 patients at 10 month follow-up. There have been no deaths in the study group. Scores of heart wall motion (segmental) improved from 2.41 before surgery to 2.09 at the 10-month mark. Global wall motion scores improved from 1.96 before surgery to 1.65. Panel moderator Dr. Timothy Gardner said that after transplant, the muscle cells change enough to look like heart muscle cells that may support contraction. He believes they are close enough to improve heart function. Regarding bone marrow stem cells, Dr. Gardner said that such cells could change enough to contract like heart muscle cells, but they also could become blood vessels and the "lattice work" of heart tissue. Researchers believe that adult stem cells are better to use than embryo stem cells. "There is an advantage to using muscle cells that are already destined to become muscle cells," he said. ======================================== Adult Cell Transplant Helps Ischemic Heart or Legs By Dr. Laurie Barclay (Medscape Medical News 2002) November 18, 2002 - Cell transplant using a person's own cells may improve ischemia in hearts and legs, according to 3 presentations here. Two trials focused on injecting bone marrow cells or skeletal muscle cells into the scarred area of a heart damaged by heart attack. In another study, injecting bone marrow cells into ischemic limbs led to new vessel growth, reducing need for amputation. Bone marrow can change into heart cells and also into smooth muscle cells, connective tissue cells and other types of cells to rebuild the entire structure of a tissue, said presenter Dr. Manuel Galinanes. He says the benefit of transplanting bone marrow into scar tissue of a heart can be seen only 6 weeks after injection. In 14 heart attack patients with low LVEF, bone marrow from the sternum was injected into scarred heart tissue during non-emergency bypass surgery. Heart wall motion measured by echo improved within weeks of treatment, and improvements lasted at least 10 months. Regional wall motion score went down, meaning less movement abnormality, from an average score of 2.41 at study start to 2.16 six weeks after treatment and 2.09 ten months after treatment. Global wall motion score also went down from 1.96 before surgery to 1.64 at six weeks, and stabilized at 1.65 after 10 months. Although it is still unproven that bone marrow creates a new cellular infrastructure in heart scar tissue, the lead researcher thinks "that is the only possible explanation." Researchers confirmed the presence of scar tissue with dobutamine stress echo before surgery, and then confirmed it again during surgery. That suggested that the affected area was non-functional and the abnormality was irreversible. They wanted to make sure they were injecting the marrow into dead tissue so the injection would not be a serious risk to the patient. In a trial supervised by the FDA, researchers safely transplanted 16 patients with skeletal muscle cells injected into hearts severely damaged by heart attack or heart failure. EF was less than 30%. Eleven patients were having bypass surgery and 5 were having an LVAD implanted. Muscle cells were extracted from thigh muscle, then grown in large quantities in the lab using a controlled cell expansion manufacturing process. These multiplied cells were injected in doses ranging from 10 million to 300 million cells. "Our findings will allow us to move forward with testing if the procedure can improve the heart's contraction," says lead author Dr. Nabil Dib from the Arizona Heart Institute in Phoenix. "We found that the transplanted muscle cells survived and thrived in patients. Areas damaged by heart attack and heart disease showed evidence of repair and functioning." Twelve weeks after transplant, average EF improved from 23% to 36%. Echo, MRI, and PET scan showed evidence of regeneration in the area injected. There were no major adverse events related to the cell transplant procedure at 9-month follow-up. The third study showed that bone marrow cells implanted into ischemic legs in patients with peripheral arterial disease (PAD) formed new blood vessels, increased blood flow, and prevented amputation. The lead author was Dr. Hiroya Masaki. In this randomized trial, 45 PAD patients got injections of their own bone marrow cells into the calf muscles. Compared with controls who received placebo injections, patients getting bone marrow cell transplants had a "striking" increase in new capillary formation and in new, visible blood vessels. Of 45 treated patients, 31 had an increase in ankle- brachial pressure index in the treated legs, and 39 had decreased rest pain with improved treadmill endurance. Ischemic ulcers or gangrene healed in 21 of 28 treated legs.