Pharmacological approach to induction of mitochondrial biogenesis for rapid maturation and functional differentiation of stem/progenitor cells in the heart and other tissues
Following heart disease diagnosis, traditional therapies seek to limit further damage to the heart and, ultimately, to prevent the development of heart failure and death. However, current therapies do little to reverse the damage associated with advanced heart disease, such as the fibrosis and ventricular remodeling that occur secondary to a heart attack. This technology is intended to be used as a therapy to both a) limit cardiomyocyte death in response to inflammatory conditions, and b) promote the generation of new cardiomyocytes from progenitor cells present in the heart. This technology may also be applicable to diseases of other organs, where preventing inflammation-mediated cell death and fibrosis while promoting organ regeneration would be beneficial.
This invention comprises targeted delivery of carbon monoxide (CO) to multiple organ systems to induce beneficial effects by eliciting mitochondrial biogenesis. Administration of this small-molecule drug, known as a carbon monoxide releasing molecule (CORM), creates resistance to inflammatory cell death and reduced susceptibility to energetic stress in target cells. In mouse models, this drug induces cardiac stem or progenitor cells to differentiate into cardiomyocytes. This may be especially beneficial for the treatment of patients immediately following myocardial infarction by preventing cell death, while also stimulating the growth of new heart tissue. Additionally, co-administration of this drug with the infusion of allogeneic or autologous stem cells may increase the differentiation rate and engraftment in the target organ.
This drug may be beneficial beyond heart diseases, such as in diseases of the liver, lung, or kidney.
Current standard seeks to limit damage to the organ, slowing progression to end stage disease. This technology limits damage through a novel mechanism, while also promoting regeneration of the damaged tissue. This technology could also be used in conjunction with stem cell therapy to improve efficacy.