Leigh Syndrome
Currently, the treatment of Leigh syndrome is mainly supportive care with limited efficacy. At Protheragen, we focus on developing novel therapeutics and building accurate animal models to accelerate preclinical studies of potential therapies for Leigh syndrome. Our expertise ensures that client's research receives the most reliable and relevant support, accelerating their drug development journey.
Introduction to Leigh Syndrome
Leigh syndrome, also known as subacute necrotizing encephalomyelopathy, is a severe, progressive mitochondrial disorder characterized by bilateral symmetric brainstem and basal ganglia lesions, leading to neurological deterioration and early mortality. It represents one of the most common pediatric mitochondrial diseases, with an estimated incidence of 1 in 40,000 live births.
Fig.1 Clinical features of Leigh syndrome. (Bakare A B, et al., 2021)
Pathogenesis of Leigh Syndrome
Leigh syndrome is fundamentally caused by defective mitochondrial oxidative phosphorylation due to mutations in either nuclear or mitochondrial DNA-encoded respiratory chain components, leading to severe ATP depletion, lactic acidosis, and selective neurodegeneration in basal ganglia and brainstem regions.
Fig.2 Genes involved in Leigh syndrome pathogenesis. (Lee J S, et al., 2020)
Therapeutic Development for Leigh Syndrome
| Drug Names | Mechanism of Action | Targets | NCT Number | Research Phase |
| TTI-0102 | Small molecule stabilizer of mitochondrial complex I assembly | Mitochondrial complex I subunits | NCT06990984 | Phase II |
| ABI-009 | mTOR inhibitor reducing cellular energy demands and improving metabolic flexibility | mTOR pathway | NCT03747328 | Phase II |
| EPI-743 | Synthetic benzoquinone that enhances mitochondrial electron transport and reduces oxidative stress | Mitochondrial complex I/III | NCT02352896 | Phase II |
| RP103 | Increases glutathione levels to combat oxidative stress in mitochondria | Lysosomal cystine accumulation | NCT02023866 | Phase II/III |
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
Recognizing the complexity of diagnosing and treating Leigh syndrome, Protheragen is committed to building a team of experts to provide cutting-edge diagnostic and therapeutic development solutions. Our commitment lies in providing a variety of customized therapy development services to meet the diverse research needs of our customers. We also excel in generating precise disease models that are carefully engineered to replicate the unique features of Leigh syndrome.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Ndufs4 Knockout Mouse Model: Recapitulate Leigh syndrome's severe neurodegenerative phenotype with bilateral striatal lesions, lactic acidosis, and premature lethality.
- FOXRED1 Silence Model: Demonstrate mitochondrial respiration defects and neuronal vulnerability.
Protheragen takes great pride in providing integrated preclinical services for Leigh syndrome. These services cover all aspects of drug research including pharmacodynamics (PD), pharmacokinetics (PK), and safety. We observe the highest quality and ethics in the execution of all our research services to make certain the outcome is dependable. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Bakare A B, Lesnefsky E J, Iyer S. Leigh syndrome: a tale of two genomes[J]. Frontiers in Physiology, 2021, 12: 693734.
- Lee J S, Yoo T, Lee M, et al. Genetic heterogeneity in Leigh syndrome: highlighting treatable and novel genetic causes[J]. Clinical genetics, 2020, 97(4): 586-594.