Neuregulin-1 Therapy for Heart Failure with Preserved Ejection Fraction
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Solution Overview
Problem
Current treatments for heart failure with preserved ejection fraction, also known as diastolic heart failure, are ineffective in improving clinical symptoms and prognosis, and there is a lack of specific therapies to enhance cardiac diastolic performance and prevent further deterioration.
Innovation Solution
Administration of neuregulin proteins or their functional fragments to mammals, which bind to ErbB receptors on myocardial cells, activating the ERK signaling pathway to improve myocardial cell structure and function, thereby addressing heart failure with preserved ejection fraction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for heart failure with preserved ejection fraction are used, then standard therapy is available, but clinical symptoms and prognosis are not improved
Solution Approach 1:
The patent applies parameter changes by administering neuregulin-1 at specific dosages (e.g., 2 mg every other day or 10 mg once weekly) to alter the biochemical parameters of heart failure treatment. This changes the therapeutic approach from conventional medications to growth factor-based therapy, improving clinical symptoms and prognosis while addressing the inadequacy of standard treatments
2Reliability
If neuregulin is administered to improve myocardial cell structure and function, then cardiac diastolic performance is enhanced, but the complexity of the treatment increases
Solution Approach 1:
The patent uses neuregulin-1 as an intermediary substance that mediates the improvement of cardiac diastolic performance. The growth factor acts as a biological mediator that binds to ErbB receptors on myocardial cells, activating signaling pathways to enhance sarcomere formation, cytoskeleton structure, and intercellular junctions, thereby improving cardiac function without requiring complex mechanical or surgical interventions
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The use of neuregulin significantly improves cardiac function in animal models and clinical trials by enhancing myocardial cell sarcomere formation, cytoskeleton structure, and intercellular junctions, effectively delaying or preventing the progression of heart failure with preserved ejection fraction.
Implementation Method 1
NRG binds to the extracellular domain of ErbB3 or ErbB4, it induces the formation of heterodimers of ErbB3, ErbB4 with other ErbB receptors (normally including ErbB2) or homodimers of ErbB4, which results in phosphorylation of the receptor's intracellular region. The phosphorylated intracellular domain then binds signaling proteins inside the cell, thus activating the downstream AKT or ERK signaling pathway
Data Source
AI summary
The invention provides neuregulin for use in a method of preventing, treating or delaying heart failure with preserved ejection fraction in a mammal. Also provided in the present invention is a pharmaceutical preparation for use in a method of preventing, treating or delaying heart failure with preserved ejection fraction in a mammal, wherein the pharmaceutical preparation comprises an effective amount of neuregulin.