Pathological mitochondrial hits can be recovered through drug-induced mitophagy or a fusion with healthy mitochondria, and the transplantation of healthy mitochondria has emerged as a novel therapeutic option if drugs are unable to clear damaged ones. At our company, Protheragen offers an all-inclusive, customized mitochondrial transplantation therapy development solution that includes validation and optimization of donor mitochondria for effective in vitro and in vivo efficacy testing, focused on the client's therapeutic goals and indication target.
Many human diseases derive from mitochondrial dysfunction, and the curative successes of conventional therapies are restricted. Mitochondrial transplantation therapy represents a new modality of therapy, which aims to transfer the healthy mitochondria from either normal cells or synthetic biology assembled ones into the damaged cells and tissues that are losing function, then replace their defective mitochondria and recover their functions. These healthy mitochondria can fuse with the endogenous network to help promote ATP synthesis, decrease oxidative stress, restore calcium homeostasis, and facilitate repair of damaged tissue. This direct bioenergetic supplementation provides a new modality of action different from drugs or gene therapy.
Fig.1 This schematic illustrates the sources and delivery methods of mitochondria transplantation. (Jiao, Q., et al., 2024)
Transferring exogenous functional mitochondria into the cells deficient in mitochondria may serve as a decent approach for curing or preventing mitochondria-related diseases, since it can overcome many disadvantages of drugs, such as inadequate bioavailability, resistance, and inadequate reversion back to the original cellular function. The development of mitochondrial preparation and transfer, such as direct microinjection, transfer using vesicles or liposomes, surface functionalization of mitochondria, and others, has sped up the application of this therapy.
Autologous Mitochondrial Transplantation
Utilizes mitochondria harvested from the individual's own healthy tissue and reinjected into the affected area. This circumvents the allogeneic rejection and is commonly preferred for acute, regional injuries such as myocardial ischemia-reperfusion injury in neonates or adults.
Allogeneic Mitochondrial Transplantation
Uses mitochondria, taken from a healthy, unrelated donor. This strategy is scalable, and it has been explored for situations in which autologous sources are inadequate or impaired, with the caveat that immunogenic considerations must be taken into account and managed.
| Therapy | Target Disease | Mitochondrial Source | Development Stage |
|---|---|---|---|
| PN-101 | Idiopathic Inflammatory Myopathy (IIM) | Human umbilical cord mesenchymal stem cells | Phase I/II |
| Autologous Mitochondrial Transplantation | Acute Ischemic Stroke (AIS) | Skeletal muscle | Phase I |
| Nanomotorized Mitochondria | Ischaemic Heart Disease (IHD) | Human mesenchymal stem cells | Preclinical |
| Mito-Plt | Diabetes-associated Cognitive Impairment (DACI) | Platelet | Preclinical |
| Nasal Administration of Mitochondria | Cisplatin-induced Cognitive Deficits | Human mesenchymal stem cells | 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.
Based on profound expertise in mitochondrial biology and advanced analytical platforms, as well as a successful track record of translational research, we offer a full range of services towards the development of mitochondrial therapy. Our multi-dimensional approach, including rigorous mitochondrial quality control, advanced delivery vector development, and physiologically-relevant disease modeling, de-risks and accelerates therapeutic pathways, ensuring robust and reproducible outcomes for our partners.
Protheragen supports therapy development for a broad spectrum of conditions driven by mitochondrial insufficiency, including primary mitochondrial disorders, neurodegenerative diseases, cardiovascular injuries, metabolic syndromes, and other age-related degenerative conditions. Our team collaborates closely with clients to design and execute a customized development plan that addresses the unique pathophysiology, target tissue, and delivery challenges inherent to each specific disease.
| Types | Diseases | |
|---|---|---|
| Primary Mitochondrial Diseases | Alpers Disease | Barth Syndrome |
| Carnitine Deficiency | Autosomal Dominant Optic Atrophy | |
| Chronic Progressive External Ophthalmoplegia | Short-Chain Acyl-CoA Dehydrogenase Deficiency | |
| Leigh Syndrome | Kearns-Sayre Syndrome | |
| Thymidine Kinase 2 Deficiency | Leber Hereditary Optic Neuropathy | |
| Co-Enzyme Q10 Deficience | And More | |
| Secondary Mitochondrial Diseases | Cardiovascular Diseases | Metabolic Disorders |
| Neurodegenerative Diseases | Other Conditions | |
Laying the groundwork for a safe and efficacious mitochondrial transfer therapy will necessarily take many approaches, moving beyond simple transfer to rigorous functional and safety validation. Our tailored solutions are designed to address key developmental milestones, offering flexible and customized support.
Optimization of isolation protocols to improve mitochondrial yield, purity, and function integrity from diverse sources (muscle, iPSCs). Our extensive quality control analysis (intactness test, membrane potential measurements, high-resolution respirometry (OCR/ECAR), etc.) for all preparations.
Development and testing of vehicles and new systems for delivery, including novel carriers (e.g., hydrogels, vesicles, or liposomes) as well as pressure- or magnet-driven techniques to enhance targeting and cellular uptake. Developing stabilization and protective formulations aimed at sustaining mitochondrial viability throughout the transplantation workflow.
Conduct an all-around evaluation in validated disease-specific cell-based models (e.g., primary cells, iPSC-derived cells) and relevant animal models (e.g., mice, rats) of the diseases concerned, including biodistribution and functional improvement as well as toxicity assessment, producing reliable data for development decision-making.
By engaging the dedicated team of mitochondrial scientists and therapy development specialists, you will gain a one-stop shop of services that are collectively designed to convert the hope and potential power of mitochondrial transplantation into a reality. Protheragen is dedicated to advancing your program through science, operational accuracy, and a collaborative business model. Get in touch with our team and learn how our custom development services can speed up your research.
Reference
For research use only, not for clinical use.
