miR-92 Antagonists for HFpEF Diastolic Dysfunction
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Solution Overview
Problem
Current treatments for heart failure with preserved ejection fraction (HFpEF) are ineffective, and the underlying pathophysiological mechanisms are not fully understood, leading to high morbidity and mortality rates and a lack of therapeutic options.
Innovation Solution
Development of micro-RNA (miR)-92 antagonists, particularly nucleic acid-based oligonucleotide inhibitors, to target and modulate the function of miR-92, which is implicated in cardiovascular pathologies, for the treatment of heart diseases associated with reduced ventricular elasticity and diastolic dysfunction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional pharmacological treatments targeting the renin-angiotensin-aldosterone system and adrenergic nervous system are used, then treatment coverage is provided, but no significant benefit in reducing morbidity and mortality is achieved
Solution Approach 1:
The patent shifts the therapeutic parameter from targeting conventional cardiovascular systems (renin-angiotensin-aldosterone, adrenergic) to targeting microRNA pathways, specifically miR-92 and its target ELN. This fundamental parameter change enables therapeutic effect in HFpEF where conventional parameters have failed.
Solution Approach 2:
The patent introduces miR-92 antagonists as intermediary molecules that mediate the therapeutic effect by blocking miR-92 activity and thereby upregulating ELN expression. This intermediary approach provides a new mechanism of action distinct from conventional direct cardiovascular drug targets.
2Adaptability or versatility
If microRNA-based treatments are developed, then novel therapeutic mechanisms are introduced, but the underlying pathophysiological mechanisms are not fully understood
Solution Approach 1:
The patent performs preliminary identification and characterization of the miR-92/ELN axis as a therapeutic target before full pathophysiological understanding is achieved. Clinical trials are initiated based on preclinical evidence and mechanistic plausibility, allowing therapeutic development to proceed while research continues.
3Reliability
If miR-92 antagonists are administered, then miR-92 activity is inhibited and ELN expression is upregulated, but the exact mechanism by which this improves HFpEF outcomes is not fully elucidated
Solution Approach 1:
The patent extracts and isolates the specific miR-92/ELN molecular axis from the complex HFpEF pathophysiology to develop a targeted therapeutic intervention. By focusing on this specific pathway, the patent simplifies the therapeutic approach while addressing the multifaceted nature of HFpEF.
Data Source
AI summary
The invention pertains to a compounds or compositions comprising antagonists of miR-92 which are useful in a method of treatment of a heart disease associated with or caused by a reduced ventricular elasticity and/or a diastolic dysfunction in a subject, which preferably is a subject suffering from Heart Failure with preserved Ejection Fraction (HFpEF). The invention provides such compounds and/or compositions, which are preferably nucleic acid based antagonists of miR-92, preferably oligonucleotide inhibitors, as well as uses and method for treating subjects.