Advantages:
- Identification of MRPS5 as a Therapeutic Target: Reduction of MRPS5 expression stimulates cardiomyocyte proliferation and enhances heart function
- Discovery of the MRPS5 signaling axis: Decreased MRPS5 enhances ATF4 and Knl1, which promote cardiomyocyte, boosting cardiac recovery after myocardial injury
- Improved Survival and Cardiac Function in Preclinical Models: Improvements in survival rates and cardiac health in mouse models with cardiac dysfunction
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.
The above image shows representative images and quantification of EdU-positive (F), pH3-positive (G), and Aurora B-positive (H) cardiomyocytes in hearts from doxycycline-treated and control mice. In all sections, cardiomyocytes were stained with cell proliferation markers: EdU (green), pH3 (green), and Aurora B (green), alongside the cardiomyocyte marker cTnT (red) and nucleus marker DAPI (blue). These images provide insights into cell proliferation, with a scale bar of 20 μm for all heart sections. The quantification highlights the differences between doxycycline-treated and control groups in terms of cardiomyocyte proliferation.
Desired Partnerships
- License
- Sponsored Research
- Co-Development