Advantages:
- Novel Mitochondrial Target Driving Cardiomyocyte Proliferation
- Enables regeneration of functional heart muscle, going beyond symptomatic treatment
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Induces cardiomyocyte proliferation while preserving overall mitochondrial function
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In Vivo Proof-of-Concept Showing Improved Cardiac Function and Reduced Infarct Size
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Amenable to Multiple Therapeutic Modalities (Small Molecules, RNA Modulation, or Gene-Based Approaches)
Summary:
The limited regenerative capacity of the adult mammalian heart poses a significant challenge for myocardial injury recovery. Existing treatments primarily manage symptoms and prevent further damage but fail to regenerate lost heart tissue. Consequently, there is an urgent need for targeted therapies to enhance cardiomyocyte proliferation and heart regeneration.
This invention explores a novel approach to repairing damaged hearts by modulating mitochondrial translation, specifically focusing on the mitochondrial ribosomal protein S5 (MRPS5), a protein that controls mitochondrial protein translation. Research demonstrated that reducing MRPS5 expression in cardiomyocytes triggers a mitochondrial stress response that activates the transcription factor ATF4, leading to the upregulation of cell division genes and increased cardiomyocyte proliferation. Mouse models with reduced MRPS5 demonstrated improved cardiac function, smaller infarct sizes after myocardial infarction, and enhanced heart regeneration without significantly impacting overall mitochondrial function.
In summary, inhibiting MRPS5 through genetic deletion or doxycycline treatment, offers a new strategy to enhance heart regeneration and repair and represents a new potential therapy for heart disease.
MRPS5 inhibition drives cardiomyocyte proliferation and cardiac repair following myocardial injury. Representative images and quantification of cardiomyocytes from control and doxycycline-treated mice demonstrate increased proliferation upon MRPS5 suppression. Cardiomyocytes are labeled with proliferation markers EdU, phospho-histone H3 (pH3), and Aurora B (green), alongside the cardiomyocyte marker cTnT (red) and nuclear stain DAPI (blue). MRPS5 inhibition significantly enhances the proportion of proliferating cardiomyocytes, consistent with activation of regenerative pathways. These findings correlate with improved cardiac function and reduced injury in vivo, supporting MRPS5 as a promising target for heart regeneration. Scale bar: 20 μm.
Desired Partnerships
- License
- Sponsored Research
- Co-Development