Bio-Leonhardt
A Breakthrough in Heart Regeneration Therapy

For heart failure patients, the notion of total heart regeneration is the elixir of life. Heart failure is a significant health problem worldwide with substantial unmet medical needs. Approximately 805,000 people annually experience a heart attack in the United States alone. Additionally, over 6.5 million people in the U.S. suffer from heart failure, where the heart is damaged and cannot pump enough blood to meet the body’s needs. Of this group, 1.1 million are in advanced Class III and IV heart failure.

Causes of heart failure include heart attack from coronary artery occlusion – blocked blood flow in an artery that causes damage to the heart muscle and scarring – and cardiomyopathy, an underlying disease of cardiac muscle cells, called cardiomyocytes (CMs). CMs are responsible for generating contractile force in the heart to pump blood to meet the organism’s needs. CMs undergo enlargement (hypertrophy) in response to chronic demand for increased contractile force. Once the heart muscle is damaged, it has an extremely limited capacity to self-replicate, and it is unable to generate enough CMs to replace the damaged tissue. In their place, the heart produces scar tissue to preserve its structural integrity. Heart scar tissue remains for life and impairs the heart’s ability to pump blood, leading to heart failure, frequent hospitalizations, and eventually death.

Numerous pharmacological interventions, implantable devices, and surgical techniques developed in the of last 50 years have dramatically improved outcomes and quality life for patients with heart failure. In advanced and end-stage Class III and IV heart failure, this includes implanted mechanical ventricular assist devices (mechanical pumps) or heart transplantation which are expensive and associated with significant risks.

However, mortality rates have plateaued in the previous two decades because current interventions slow disease progression but do not reverse heart disease. This is likely due to the minimal regenerative capacity of the adult mammalian heart, the relative inability of CMs within the adult heart to reenter the cell cycle, and a lack of naturally occurring stem cells that can reproduce all cell types within the heart following injury.

Although multiple heart regeneration studies have been conducted – including some of the most promising attempts to regenerate CMs by injecting stem cell-derived CMs and transplantation of engineered stem cell-derived heart tissue – none have demonstrated the ability to reverse heart failure completely. The biggest hurdle to implementing stem cellderived therapy is the lack of a sufficient number of CMs (e.g., multiple billions) needed per patient. Targeting class three and four heart failure patients, Bio-Leonhardt assimilated the scientific findings from these studies to develop a novel, path-breaking treatment to regenerate the heart. Early studies demonstrated that injecting stem cells into fibrotic cardiac scar tissue led to the formation of fibroblasts, not muscle. The company then fused immature myoblasts from skeletal muscle with host CMs to overcome this challenge.

The rationale behind selecting immature myoblasts was to establish the necessary blood supply to the scar tissue to create robust cells that can survive, graft, and build active heart muscle.

The Bio-Leonhardt system combines precise bioelectric signaling of regenerative protein expressions and repeat deliveries of muscle stem cells and biologic support factors to improve the muscle stem cells’ engraftment, survival, and differentiation into new heart muscle. In company studies, this protocol demonstrated substantial improvement in the functional capacity of patients’ hearts.

The company has developed bioelectric signals that control the specific protein expressions required to grow new blood vessels, muscles, and nerves. Patented bioelectric signal sequences are used for homing, proliferating, and differentiating stem cells into new heart muscle in the myocardial scar tissue. In addition, the company has combined its patent-pending Klotho expression bioelectric stimulation technology with Klotho expressing mesenchymal stem cell (MSCs) technology to increase Klotho. This potent antiaging protein plays an essential role in muscle regeneration.
Furthermore, the system manages inflammation and cell retention, survival, and proliferation. Bioelectric signaling sequences for Follistatin and Tropoelastin that enable muscle regeneration and recovery and increase the elasticity of heart muscles, the aorta, and coronary arteries are also incorporated. The system monitors inflammation in real-time and then bioelectrically delivers signals to stimulate inflammationfighting proteins to help patients recover from advanced heart failure. Bio-Leonhardt also focuses on reducing the size of the heart and improving its ability to contract.

In contrast to previous interventions, the Bio-Leonhardt system incorporates repeated daily, weekly, or monthly infusions of muscle stem cells and a composition of support factors including exosomes, alkaloids, micro RNAs, nutrient hydrogel, Follistatin, and SDF-1 to regenerate damaged heart muscle. The muscle stem cells and support actors are delivered via slow micro pump infusion.

Bio-Leonhardt System Patented Protein Signals and Targeted Functions

“Unlike competitors, Bio-Leonhardt simplifies the process by stimulating cell therapy and delivering growth factors simultaneously,” stated Howard Leonhardt, Chairman of the Board and CEO of Bio-Leonhardt. Bio-Leonhardt envisions reprogramming existing cardiac resynchronization therapy, such as implantable cardioverter-defibrillators, and transforming it with signals to release regenerative proteins. The company has developed a micro-stimulator and refillable infusion pump, which can be implanted under the patients’ skin to deliver the therapy. A second-generation combination stimulator/infusion pump and a noninvasive method to provide regenerative signals are in development.

Bio-Leonhardt’s heart regeneration technology promises to be a medical practice-changing, cost-effective treatment for patients to overcome debilitating and often fatal heart conditions.