Mitochondrial Cardiomyopathy
Mitochondrial cardiomyopathy exhibits an abnormality in morphology and the function of the heart muscle. This condition stems from mutations either in the nuclear genome or mitochondrial DNA (mtDNA). Disorders of abnormality in mitochondria are most often associated with mitochondrial cardiomyopathy. Protheragen is an industry research service provider engaged in developing rare cardiovascular disease drugs, paying particular attention to mitochondrial cardiomyopathy.
Overview of Mitochondrial Cardiomyopathy
Mitochondrial cardiomyopathy is defined as a type of myocardial disease that results from mutations in either the mtDNA or mitochondria-associated nuclear DNA (nDNA), and manifests as an abnormal beating heart, structurally and/or functionally altered, without coexisting hypertension, valvular disease, or other congenital heart disease. Given the population estimates of mitochondrial disorders and the frequency of cardiac involvement, approximately 1 in 10,000 to 1 in 15,000 individuals in the general population are affected.
Fig.1 Common mitochondrial cardiomyopathy complications. (Yang, J., et al., 2022)Pathogenesis of Mitochondrial Cardiomyopathy
In the past twenty-five years, there has been remarkable advancement in genetic research focused on elucidating the molecular etiology of mitochondrial cardiomyopathy. Types of mutations have surpassed the one-thousand mark across different genes with differing ontologies. Genetic variants with mitochondrial pathologic potential such as mtDNA deletions, and nuclear and mtDNA variations disrupt the scaffolding of the MRC complexes, tRNA, rRNA, and coenzyme Q10 biosynthesis which contributes to numerous pathogenic mechanisms underlying hypertrophic, dilated, restrictive, and arrhythmogenic cardiomyopathy.
Fig.2 Effects of mtDNA heteroplasmy levels on cardiomyocyte pathology. (Pavez-Giani, M. G., and Cyganek, L., 2022)Therapeutics Development for Mitochondrial Cardiomyopathy
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
|---|---|---|---|---|
| OMT-28 | Inhibits the generation of mitochondrial reactive oxygen species, enhancing the metabolism and function of the mitochondria. | PPARα | NCT05972954 | Phase II |
| rhAVV 10- based gene therapy | Swiftly restore and reorganize the cardiomyocytes with profound energy deficiency and structural distortion, reversing the cardiomyopathy entirely in the mice. | FXN | / | Preclinical |
| 1-Deoxynojirimycin | Correct the mitochondrial function by directing the optic atrophy protein 1 (OPA1) to increase oligomerization which restores cristae structure within the mitochondria. | OPA1 | / | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen focuses on the innovation of therapeutics, and we have integrated all services of diagnostics, therapeutic development, and advanced disease model creation into a single platform. With us, every client is guaranteed bespoke multi-dimensional solutions supporting strategic decisions throughout the pharmaceutical development continuum that advance drug development processes.
Therapeutic Development Services
Diverse Platforms
Animal Model Development for Mitochondrial Cardiomyopathy
Protheragen uses cutting-edge technology to create and implement comprehensive animal models of mitochondrial cardiomyopathy which are crucial in providing a basis for understanding the different mechanisms and developing therapies that entail mitochondrial cardiomyopathies.
Genetically Engineered Animal Model
The animal models are developed by altering specific genes within the mitochondrion, including those related to oxidative phosphorylation, energy metabolism, and other pertinent processes.
Optional models:
- Ant1 deficient model
- Med30zg mutation model
- Ndufs6 knockout model
- TFAM mutation model
- CHCHD2/CHCHD10 DKO model
- Isca1 knockout model
- C1QBP conditional knockout model
- Other models
Along with our tailored diagnostic and therapeutic development services, Protheragen provides a complete range of preclinical services which include pharmacokinetics studies and detailed assessments of drug safety. Through our extensive methodological and innovative research approaches, we are able to transcend the boundaries between applied scientific discovery and application, guaranteeing optimal progression toward viable therapies. Contact us for further inquiries about our services.
References
- Yang, Jinjuan et al. "Mitochondrial Cardiomyopathy: Molecular Epidemiology, Diagnosis, Models, and Therapeutic Management." Cells 11.21 (2022): 3511.
- Pavez-Giani, Mario G, and Lukas Cyganek. "Recent Advances in Modeling Mitochondrial Cardiomyopathy Using Human Induced Pluripotent Stem Cells." Frontiers in cell and developmental biology 9 (2022): 800529.
For research use only, not for clinical use.