Mitochondrial diseases are a diversified genetically heterogeneous category of metabolic disorders defined by defects in oxidative phosphorylation (OXPHOS). Protheragen delivers comprehensive, custom research services to meet the uniquely defined needs of the issues related to the mechanisms and therapeutics of these disorders, providing professional services in the areas of diagnostics, therapeutics, model development, and extensive mitochondrial phenotyping.
Overview of Mitochondrial Diseases
Mitochondria are found in almost all eukaryotes and play a crucial role in many aspects of cellular life, primarily through energy production and cellular respiration. Damaged and dysfunctional mitochondria are unable to produce sufficient energy to supply high-energy tissues, such as the heart, brain, and muscles; therefore, many diseases originate from them. Mitochondrial diseases span many presentations and occur in approximately 1 in 5000 live births.
Fig.1 Cell signaling pathways converge on mitochondria. (Zong, Y., et al., 2024)
Types of Mitochondrial Diseases
- Primary Mitochondrial Disease (PMD)
Primary mitochondrial disease is due to genetic abnormalities affecting the mitochondrial respiratory chain or its functionality. These diseases result from damaging variants in either mitochondrial (mtDNA) or nuclear (nDNA) genes responsible for encoding structural subunits, assembly factors, or proteins vital to the maintenance and translation of mitochondrial DNA.
- Secondary Mitochondrial Disease (SMD)
Secondary mitochondrial dysfunction is the result of having mitochondrial impairments in terms of structure, biogenesis, or function. It is the result of having some other primary disease process, exposure to toxins, or some form of metabolic disturbance. It is often seen in conjunction with neurodegenerative diseases, metabolic syndromes, and many others.
Therapeutics Development for Mitochondrial Diseases
| Drugs |
Target Disease |
Target |
Development Stage |
| Elamipretide |
Leber Hereditary Optic Neuropathy (LHON) |
mPTP |
Phase II |
| NFS-02 |
Leber Hereditary Optic Neuropathy (LHON) |
MT-ND1 |
Phase I/II |
| Zagociguat |
MELAS Syndrome |
sGC |
Phase II |
| TTI-0102 |
MELAS Syndrome |
Cysteamine |
Phase II |
| Deoxythymidine |
Mitochondrial DNA Depletion Syndrome |
Thymidine Kinase 2 |
Phase II |
| MIN-102 |
Friedreich Ataxia |
PPAR |
Phase II |
| REN001 |
Mitochondrial Myopathy |
PPAR |
Phase II/III |
| Resveratrol |
Mitochondrial Myopathy |
STACs |
NA |
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
Drawing on our state-of-the-art technology and deep understanding of mitochondrial biology and genetics, as well as our multidisciplinary teams of experts, we provide fully integrated services, which include diagnostics, therapeutics, disease models development, and mitochondrial analysis services. Our services aim to accelerate the path from discovery to therapy for mitochondrial disorders by furnishing dependable data, validated models, and useful insights.
Multiple Mitochondrial Disease Research
Recognizing the distinct pathogenesis and requirements of each condition, which can vary from multi-system disorders that broadly affect energy-intensive organs to those with primary manifestations in specific tissues such as the brain, eyes, muscle, or heart, we provide fully customized research programs. Our services are designed to be a fit-for-purpose approach based on your project requirements, whether it's tackling the complex organ-to-organ crosstalk in systemic mitochondrial diseases or investigating the focused pathophysiology of organ-specific mitochondrial diseases, and they are created to support all stages of research from mechanism discovery through therapeutic assessment.
Customized Solutions for Mitochondrial Diseases
With state-of-the-art genomic, transcriptomic, and proteomic technologies, we provide an accurate genetic variant identification and functional validation on both mtDNA and nuclear genes implicated in the molecular pathogenesis of mitochondrial disorders. We provide the development and validation of new biochemical and molecular biomarkers, enabling the most precise diagnosis and therapy monitoring.
Starting from high-throughput in vitro screening of libraries of compounds against mitochondrial targets to more detailed studies on the efficacy and mechanism of action in complex models, we support an entire preclinical drug development pipeline. We also support lead optimization, pharmacokinetic analysis, toxicity assessment, and preclinical study design to support the generation of robust data.
We develop and characterize a variety of pragmatic disease models, including patient-derived cell lines (fibroblasts, iPSCs), differentiated cell types (neurons, cardiomyocytes), and animal models that mirror salient genetic and biochemical features of human mitochondrial diseases. These models are essential for mechanism studies and therapeutic testing.
A broad range of analytical suites covers the phenotyping of mitochondrial health and function down to the most minute details, including assays for oxygen consumption rate (OCR), extracellular acidification rate (ECAR), mitochondrial membrane potential, reactive oxygen species production, ATP levels, and mitochondrial network morphology using live-cell imaging.
Contact Us
Dedicated to being a strategic partner in global mitochondrial diseases research, Protheragen offers rigorous, innovative, and bespoke solutions. To discuss how our integrated services can advance your specific program, please contact our team of specialists for a detailed consultation.
Reference
- Zong, Yao et al. "Mitochondrial dysfunction: mechanisms and advances in therapy." Signal transduction and targeted therapy 9.1 (2024): 124.
