Biotherapeutic Product Candidate for the treatment of chronic atrial fibrillation

With more than 3 million patients in the U.S., atrial fibrillation is the most common arrhythmia in clinical practice. Attempting to establish and maintain regular sinus rhythm in the long term, drug therapy is known to have only a modest action in treating these patients. Drugs also have various side-effects and a significant number of patients discontinue taking their medications consistently. Alternatively, non-pharmacological approaches have been developed in the last years, such as pulmonary vein isolation. However, the rate of success is still to be determined and not every patient is eligible to these procedures. For symptomatic patients where all pharmacological and non-pharmacological approaches have failed, atrioventricular node ablation, i.e. the destruction of tissue where electrical signals are aberrant and lead to arrhythmias, becomes the only resource for rate control. This technique is well established and the symptoms are controlled in the vast majority of patients. However, this approach creates the necessity for a permanent pacemaker implantation.

Significant advances have been made recently by scientists in the areas of tissue engineering and cell therapy, where the guiding principle consists to use a body’s own tools and mechanisms to repair disease. For years, Symphony Medical’s collaborators have translated the application of tissue and cell engineering (biotherapeutics) to the treatment of heart dysfunctions and, more concretely, atrial fibrillation. Various preclinical models have confirmed that it is possible that some specific cell population or a combination of cells, biopolymers, or growth factors, can establish electromechanical connections with the host myocardium to modify and regulate the aberrant conductivity.

A modification of conductivity with biotherapeutics has significant potential as an alternative for atrial fibrillation patients. The objective of Symphony Medical’s treatment consists of a permanent reduction in the ventricular rate without inducing complete atrioventricular (AV) block, and, consequently, without the need of a pacemaker. This is accomplished by delivering a predetermined number of cells and/or biopolymers to the AV node, one of the most important components of the cardiac electric conduction system, through a catheter device. Symphony Medical’s first generation product (in advanced preclinical stage) utilizes a patient’s own skin fibroblasts which are obtained from a small skin sample and cultured in a laboratory 2-3 weeks before the procedure. The company is also developing an alternative approach (in early preclinical stage) whereby biopolymers are injected instead of cells in order to attract and provide an adequate matrix for cells.

In 2005 and 2006, research teams at the Mayo Clinic Rochester and the American Cardiovascular Research Institute (ACRI) in Atlanta confirmed in preclinical models the feasibility of using Symphony Medical’s treatment for atrial fibrillation by modifying the AV node with autologous fibroblasts (See News Room). Concretely, both studies concluded as follows:

• Fibroblasts could be injected into the AV node and identified 4 weeks later.
• Fibroblasts had a sustained impact on AV node conduction during sinus rhythm, pacing, and atrial fibrillation in comparison to controls.
• Ventricular rate control could be achieved without creation of heart block.

Symphony Medical is presently engaged in research to further define the exact role of the implanted cells in terms of their interactions with proteins expressed locally, with the extracellular matrix that they adhere to, and with other cells functioning in adjacent areas. The company expects to initiate a clinical trial by 2009.