Mitochondria-targeted Drug Development
Mitochondria-targeted drugs are defined as those therapeutic agents that employ specific delivery technology to transport active drug molecules to the mitochondria. Leveraging our strong capabilities in developing mitochondria-targeted drugs, Protheragen is able to offer customized approaches and full-service supporting solutions to proprietary research for transitioning into commercialization frameworks of therapies for rare neurological diseases.
Overview of Mitochondria-targeted Drugs
Mitochondrial dysfunction is crucial in the development of many neurological disorders since these organelles are important for energy production and maintenance of cellular homeostasis. Mitochondria-targeted drugs are compounds meant to actually localize within and work in mitochondria and seek to restore mitochondrial function, alleviate oxidative stress, and slow down neurodegenerative processes. Mitochondria-targeted drugs may aid in mitigating neuronal damage and, in consequence, the progression of neurological diseases by acting on these fundamental cellular powerhouses.
Fig.1 Neurodegeneration is characterized by mitochondrial dysfunction. (Plascencia-Villa G, Perry G., 2023)Mechanisms of Action of Mitochondria-targeted Drugs
Mitochondria-targeted drugs exert therapeutic effects through four primary mechanisms:
- Reactive Oxygen Species (ROS) Scavenging: Mitochondria-targeted drugs combat oxidative stress by effectively scavenging the harmful reactive oxygen species within the mitochondria.
- Energy Metabolism Restoration: These drugs assist in the restoration and optimization of energy production processes within the mitochondria as it in turn, supports cell functions and overall health.
- Mitochondrial Dynamics Regulation: Mitochondria-targeted drugs assist in balancing the fusion and fission of the mitochondria, thus enhancing the health and physiological functions of organelles.
- Calcium Homeostasis & mPTP Inhibition: These drugs help in the preservation of intracellular calcium homeostasis and mitigate the development of mitochondrial dysfunction by controlling the levels of calcium and inhibiting mitochondrial permeability transition pore (mPTP).
- Mitophagy Enhancement: Mitochondria-targeted drugs facilitate the process of mitophagy to selectively remove damaged mitochondria for enhanced cellular quality control and improved overall mitochondrial health.
Fig.2 Overview of multiple mitochondrial targeted drug delivery systems. (Li Q, Huang Y., 2020)
Development of Mitochondria-targeted Drugs
| Drug Names | Indications | Targets | Mechanism of Action | Phase |
| Elamipretide | Multiple sclerosis | Cardiolipin | Binds and stabilizes inner mitochondrial membrane | Phase II |
| Nicotinamide Riboside | Friedreich's ataxia | NAD+ synthetase enzymes | NAD+ precursor boosting mitochondrial NAD+ | Phase III |
| MitoTEMPO | Stroke | Mitochondrial superoxide | SOD2 mimetic conjugated to TPP+ | Preclinical |
| EPI-589 | Rett syndrome | Glutathione reductase | Redox-active mitochondrial stabilizer | Phase II |
| DecylTPP | Leigh syndrome | Complex I | Bypasses complex I defect via alternative pathway | Phase I |
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
At Protheragen, we are committed to providing state-of-the-art mitochondria-targeted drug development services specifically for rare neurological disorders. Our expertise focuses on developing a broad range of innovative therapies and conducting rigorous evaluations in carefully designed disease models at the preclinical stage. We use a variety of targeted delivery systems, such as mitochondrial targeting peptides or ligands, nanocarriers, and liposomes, to achieve the selective delivery of mitochondria-targeted drugs, thereby enhancing their therapeutic potential.
Diversified Development Platforms for Mitochondria-targeted Drugs
Workflow of Mitochondria-targeted Drug Development
Target Identification & Validation
Drug Design & Optimization
In Vitro Characterization
IND-Enabling Studies
Safety Assessment
In Vivo Efficacy Testing
Targets of Mitochondria-targeted Drug Development
Our scientists are skilled in developing mitochondrial targeted drugs for the following targets to meet the diverse therapeutic development needs of our customers. We are committed to innovation and precision, and the solutions we provide pave the way for effective treatments in the field of rare neurological diseases.
- Mitochondrial superoxide
- 8-oxoguanine
- Complex I
- ATP synthase
- Cardiolipin
- mPTP pore
- PINK1/Parkin
- BNIP3/NIX
- NAMPT/NMNAT1
- SIRT3
- Voltage-dependent anion channel
- Mitochondrial calcium uniporter
- Drp1
- OPA1/MFN1-2
- More
Specializing in preclinical research for mitochondria-targeted drug development, Protheragen offers a comprehensive solution that includes pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies to thoroughly validate and optimize therapies for rare neurological disorders. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Plascencia-Villa G, Perry G. Exploring molecular targets for mitochondrial therapies in neurodegenerative diseases[J]. International Journal of Molecular Sciences, 2023, 24(15): 12486.
- Li Q, Huang Y. Mitochondrial targeted strategies and their application for cancer and other diseases treatment[J]. Journal of Pharmaceutical Investigation, 2020, 50: 271-293.