Problem

Cardiovascular diseases (CVDs) such as heart failure, myocardial infarction, and cardiomyopathies remain leading causes of death worldwide. Notably, heart failure is the only major cardiovascular condition still increasing in prevalence. Current treatments primarily consist in managing the symptoms rather than addressing the underlying metabolic dysfunction and consequential induction of adverse cardiac remodeling, key contributors to heart failure progression. With more than 500,000 new diagnoses of cardiomyopathy and heart failure every three years, a dire need exists for treatments that suppress adverse remodeling in diseased hearts to improve function and outcomes

Solution

Researchers at The Ohio State University have developed a gene therapy solution that enables the precise modulation of carnitine palmitoyl transferase 1a (CPT1a) expression, influencing critical cardiac functions and cell survival mechanisms. CPT1a plays a role in the metabolism of the primary fuel for the heart, long-chain fats, which is disrupted over the pathogenesis of heart failure and which CPT1a overexpression stabilizes. Preclinical studies in mice showed that increasing CPT1a expression in the pathologically stressed heart preserves ejection fraction, fractional shortening, diastolic function, and contractility, thus offering protection against functional decline during hypertrophic decompensation. Importantly, CPT1a overexpression proved effective in reducing the progression to heart failure, even after presentation of impaired cardiac function

Applications

Prevention and treatment of several CVDs by:

• Suppressing maladaptive gene activation in diseased hearts
• Reducing adverse remodeling of cardiac function, hypertrophy, and fibrosis
• Mitigating metabolic dysfunction in cardiomyopathies
• Combination therapy for acquired and congenital heart disease

Advantages

• Mechanism-based approach: this treatment targets the root causes of adverse remodeling by suppressing gene programs for hypertrophy, fibrosis, and cell death rather than the symptoms
• Improved cardiac function: CPT1a modulation preserves ejection fraction and diastolic function, ensuring better overall heart function during hypertrophic decompensation
• Long-term effects: gene therapy has the potential to be a one-time therapy as compared to the requirement of chronic drug dosing
• Optimized energy production: the technology promotes efficient energy utilization under chronic pressure overload
• Cardiac-specific delivery to affected heart muscle cells

Seeking opportunities for out-licensing and collaboration