Modulation of Retinoic Acid Metabolism as a Treatment for Heart Failure and Sudden Cardiac Death

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Unmet Need
Heart failure (HF) is a major public health problem, with a prevalence of over 5.8 million cases in the USA and over 23 million worldwide. Arrhythmogenic sudden cardiac death (SCD) further claims up to 400,000 lives annually.
Transcriptomic data from a guinea pig model of HF/SCD revealed a specific growth factor to be highly upregulated in the HF/SCD group. Little is known about this growth factor, but it appears to have proliferation-inducing properties and is highly expressed in myogenic tissue. The role of this growth factor in the heart is unknown and has never been associated with HF. It is speculated that this factor may be involved in muscle regeneration or differentiation.
Additional experimental data from another guinea pig model suggested that impaired Vitamin A metabolism may be involved in HF/SCD pathogenesis. The data support a causal role for a bioactive retinoic acid metabolite in the pathogenesis of pressure overload-induced cardiac hypertrophy (HYP) and susceptibility to SCD. Therefore, any intervention that could prevent or reverse this metabolite deficiency might represent a novel therapeutic target in the context of HF and HYP. These discoveries represent novel, potentially heart-specific targets and therapeutic interventions in the context of HYP, HF and SCD.
Technology Overview
This invention proposes therapies for HF by targeting an identified growth factor or its receptor. Inhibition or activation of the receptor for the identified growth factor may be beneficial in either HF-related fibrosis or cardiac muscle regeneration, respectively. In addition, a bioactive retinoic acid metabolite and its metabolic pathway indicate that agonists/inhibitors might prevent or reverse deficiencies in the retinoic acid pathway. Together these discoveries might represent potential options in preventing and treating heart failure and sudden cardiac death, particularly among patients who do not respond to status quo treatments.
Stage of Development
Researchers have identified a growth factor and a retinoic acid metabolite and have conducted preliminary animal testing to evaluate these targets in the treatment of cardiac hypertrophy, heart failure and sudden cardiac death.
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Sonriza Ford
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