Secondary mitochondrial diseases encompass a large group of diseases in which the mitochondria are dysfunctional as a result of other major insults, which could be genetic, metabolic, or environmental, as opposed to primary mutations in either the mitochondrial DNA or nuclear DNA that codes for mitochondrial proteins. Protheragen provides custom, comprehensive research and development services to address the complex nature of the pathophysiological processes of these diseases and to expedite the development of accurate diagnostics and therapeutics for these diseases.
Overview of Secondary Mitochondrial Diseases
As opposed to primary mitochondrial conditions caused by mutations within nuclear DNA or mitochondrial DNA that encode for mitochondrial components, secondary mitochondrial diseases involve the acquired impairment of the mitochondria. This impairment is not the root cause but is instead a major pathological feature that originates from external stressors, other genetic predispositions for other diseases, and/or chronic illnesses. This damage to the mitochondria, including the loss of oxidative phosphorylation (OXPHOS), overproduction of reactive oxygen species (ROS), impaired mitochondrial dynamics (fission/fusion), and reduced quality control, significantly contributes to worsening the condition within the affected tissues and organs.
Fig.1 Mitochondrial genes associated with secondary mitochondrial disease. (Baker, M. J., et al., 2022)
Types of Secondary Mitochondrial Diseases
Mitochondrial dysfunction has consistently been associated with diverse pathologies in humans, necessitating specialized focus based on the primary etiology.
Metabolic Disorders
Diseases such as Type 2 diabetes mellitus (T2DM), non-alcoholic fatty liver disease (NAFLD/NASH), and obesity often demonstrate dysfunction of mitochondrial structure and function, particularly in insulin-sensitive tissues, e.g., muscle, liver, and adipose tissue.
Cardiovascular Diseases
In diseases such as heart failure and myocardial ischemia/reperfusion (I/R) injury, mitochondrial damage in cardiomyocytes results in severe energy deficit, impaired Ca2+ handling, and increased cell death.
Neurodegenerative Diseases
Mitochondrial dysfunction is a hallmark in diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS), most commonly associated with alterations in mitochondrial transport, bioenergetics, and accumulation of misfolded proteins.
Other Conditions
Mitochondrial damage is also very relevant in other types of pathologies such as drug- and toxin-induced injuries, autoimmune diseases, as well as the systemic bioenergetic failure observed in critical illness and sepsis.
Therapeutics Development for Secondary Mitochondrial Diseases
| Therapy |
Target Disease |
Target |
Development Stage |
| MTP-131 |
Skeletal Muscle Mitochondrial Dysfunction in the Elderly |
mPTP |
Phase II |
| Pioglitazone |
Type 2 Diabetes |
PPARγ |
Approved |
| Mitochondrial Transplantation |
Parkinson's Disease |
/ |
Preclinical |
| MitoQ |
Heart Failure |
Mitochondria-targeted Antioxidant |
Preclinical |
| IR-780 |
Ischemia-Reperfusion Injury |
F0F1-ATP Synthase |
Preclinical |
| TL02-59 |
Sepsis-associated Encephalopathy (SAE) |
Fgr Kinase |
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
Drawing upon the deep, niche expertise in mitochondrial biology and pathology, along with its fully integrated platform of advanced technologies from diagnostics development to full mitochondrial analysis to therapeutic identification, we provide an end-to-end service for secondary mitochondrial disease. This distinct integrated solution ensures rapid, precise insights from early discovery and validation of disease-specific biomarkers all the way through development, testing, and monitoring therapeutic intervention.
Multiple Secondary Mitochondrial Disease Research
Given the diversity of secondary mitochondrial diseases, our research offerings provide a high degree of flexibility and are entirely customized to individual research goals, disease models, or mechanism of action target pathways. Concentrated research service is available in the dissection of the degree and type of mitochondrial damage, identification of key regulatory nodes, and validation of targets across different disease states to ensure that each study has scientific rigor as well as translational relevance.
| Types |
Diseases |
| Cardiovascular Diseases |
Heart Failure, Ischemia-Reperfusion Injury, etc. |
| Metabolic Disorders |
Type 2 Diabetes, Non-alcoholic Fatty Liver Disease (NAFLD), etc. |
| Neurodegenerative Diseases |
Alzheimer's Disease, Amyotrophic Lateral Sclerosis (ALS), Huntington's Disease, Parkinson's Disease, etc. |
| Other Conditions |
Chronic Fatigue Syndrome (ME/CFS), Lactic Acidosis, Muscular Dystrophies, Sepsis, etc. |
Therapeutics Development Services for Secondary Mitochondrial Diseases
Protheragen's approaches to therapeutic development are tailored to target the underlying problem in mitochondrial dysfunction that was identified for the secondary disorder. An integrated pipeline to support the discovery and preclinical validation of drugs that restore mitochondrial health.
By Types
By Process
Animal Model Development Services for Secondary Mitochondrial Diseases
To rigorously evaluate potential therapeutic agents and to investigate disease mechanisms in vivo, we establish and characterize an animal model that embodies the primary disorder and the consequent mitochondrial pathology. Services offered are as follows: Model selection, genetic and/or pharmacological induction of secondary mitochondrial dysfunction, and full phenotypic validation through behavioral analysis, tissue-specific bioenergetic profiling, and histology.
| Model Name |
Disease Association |
Modeling Method |
| Pressure-overload Mouse Model |
Heart Failure |
Surgery Model |
| MPTP-induced Model |
Parkinson's Disease |
Induced Model |
| Left Anterior Descending (LAD) Coronary Artery Ligation Model |
Ischemia-Reperfusion Injury |
Surgery Model |
| db/db Mouse Model |
Type 2 Diabetes |
Genetically Engineering Model |
| High-fat Diet (HFD)-induced Model |
Non-alcoholic Fatty Liver Disease (NAFLD) |
Induced Model |
| 3-Nitropropionic Acid (3-NP)-induced Model |
Huntington's Disease |
Induced Model |
| APP/PS1 Transgenic Model |
Alzheimer's Disease |
Genetically Engineering Model |
| SOD1-G93A Transgenic Model |
Amyotrophic Lateral Sclerosis (ALS) |
Genetically Engineering Model |
| Cecal Ligation and Puncture (CLP)-induced Model |
Sepsis |
Surgery Model |
| … |
… |
… |
Contact Us
With a unique combination of disease-specific experience, a fully integrated research platform, and client focus, we are the leading partner in driving an understanding and therapy of complex secondary mitochondrial diseases. Protheragen's integrated services are designed to derisk and move your program quickly from concept toward preclinical validation. Contact our scientists to learn how our tailored services can meet your unique R&D needs.
Reference
- Baker, Megan J et al. "Mitochondrial biology and dysfunction in secondary mitochondrial disease." Open biology 12.12 (2022): 220274.
