MYOHEART™ (Myogenesis Heart Efficiency and Regeneration Trial)

The MyoCell™ implantation using the MyoCath™ delivery catheter system may have the potential to add a new dimension to the management of post-infarct deterioration of cardiac function in subjects with congestive heart failure. Based on pre-clinical studies, implantation of autologous skeletal myoblasts may lead to replacement of non-functioning myocardial scar with functioning muscle and improvement in myocardial performance. Preliminary data in human subjects suggest skeletal myoblast implantation at the time of CABG may lead to the same effects. In principal, myoblast implantation by catheter delivery may offer the same therapeutic benefit. The present clinical study is to be conducted primarily to evaluate the safety of MyoCell™ implantation using the MyoCath™ delivery system and secondarily to evaluate the effect on regional myocardial function post treatment.

A very promising approach to reversal or stabilization of the post-infarct remodeling process is the direct injection of regenerative cells into the myocardial infarct scar. Such cell-based therapy for cardiac repair is called "cellular cardiomyoplasty". The MyoCell™ implantation using the MyoCath™ delivery catheter system may have the potential to add a new dimension to the management of post-infarct deterioration of cardiac function in subjects with congestive heart failure. MyoCath™ is Bioheart's proprietary catheter delivery system being developed by Bioheart to facilitate MyoCell™ delivery into the myocardium via the retrograde catheterization of the left ventricular cavity. Based on pre-clinical studies, implantation of autologous skeletal myoblasts may lead to replacement of non-functioning myocardial scar with functioning muscle and improvement in myocardial performance. Preliminary data in human subjects suggest skeletal myoblast implantation at the time of CABG or via the endoventricular approach may lead to the same effects. In principle, myoblast implantation by catheter delivery may offer the same therapeutic benefit. The present clinical study is to be conducted primarily to: 1. Assess the safety and effect on myocardial function of MyoCell™ (autologous skeletal myoblast) using a dose escalation methodology following implantation into myocardial scar tissue of subjects with congestive heart failure who have experienced previous myocardial infarction(s) and have had an implantable cardioverter defibrillator (ICD) previously implanted. Safety endpoints will be the evaluation of the nature and frequency of Adverse Events during the 12-month period following MyoCell™ treatment. 2. To assess the safety and feasibility of using the transendocardial injection catheter (MyoCath™) as a system for delivering MyoCell™ into myocardial scar tissue of subjects with congestive heart failure who have experienced previous myocardial infarction(s) and have an implantable cardioverter defibrillator (ICD) previously implanted. Catheter performance will be assessed at the time of the implantation using clinical evaluation questionnaires. Safety endpoints will be the evaluation of the nature and frequency of Adverse Events from the time of implantation to the Day 14 follow-up visit. If a patient meets the baseline enrollment criteria, approximately 5-10 grams of skeletal muscle is obtained from the subject's leg muscle for myoblast isolation and expansion in vitro (MyoCell™) at a specified off site cGMP culture laboratory. The expanded myoblast cells, MyoCell™ will be implanted into the akinetic myocardial scar in the region of a previous infarct utilizing Bioheart's MyoCath™ transendocardial delivery catheter system. The MyoCath™ endoventricular device is expected to deliver the MyoCell™ autologous skeletal myoblast cells into the scarred myocardial region by steering a catheter which contains a retractable hypodermic needle to the targeted sites for implantation. This will be a dose escalation study with 4 cohort groups consisting of 5 patients each. A report of the 1 month safety data from each cohort will be presented to the Data Safety Monitoring Board for permission to go to the next higher dosage. In the first cohort of this dose escalation study, 2 injections will be performed; for the second cohort, 6 injections; for the third cohort, 18 injections; and for the fourth cohort, 27 injections, depending on the size of the infarct scar, so as to inject the entire myocardial infarct scar akinetic area. The entire study is expected to be completed during the first half of 2007, including completed enrollment as well as 12-month follow-up of the last subject.