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MELAS Syndrome

MELAS syndrome is a disorder of the mitochondria, most commonly due to the m.3243A>G mutation in the MT-TL1 gene which hinders the synthesis of mitochondrial proteins. With the groundwork laid in MELAS syndrome research, Protheragen is currently developing novel therapies to improve the management of MELAS syndrome. As a partner in MELAS syndrome drug development research, we provide industry-leading support to help achieve your research objectives.

Introduction to MELAS Syndrome

MELAS syndrome is a progressive and multi-system disorder of mitochondria that results from alterations to mitochondrial DNA (mtDNA) and affects the central nervous system (CNS) and the skeletal muscles. It is one of the most common mitochondrial disorders that occurs with a prevalence of 1 in 5000 to 10000 people. The syndrome is marked with the clinical triad of the mitochondrial encephalomyopathy, recurrent stroke-like episodes, and lactic acidosis however one might see seizures, weakness in muscles, and slow progression in neurologic functions.

Symptoms of MELAS syndrome. Fig.1 MELAS syndrome manifestations. (Fan H C, et al., 2021)

Pathogenesis of MELAS Syndrome

MELAS syndrome is mostly caused by mitochondrial DNA mutations of the MT-TL1 gene, like m.3243A>G, which occurs in the mitochondria. It disrupts protein translation in the mitochondria as well as the process of oxidative phosphorylation. This in turn causes energy depletion, excessive production of reactive oxygen species (ROS), and stroke-like episodes in the brain and muscle tissue which is metabolically active because of the mitochondria.

Effects of the pathogenic mitochondrial DNA 3243A>G mutation. Fig.2 Pathogenic mitochondrial DNA 3243A>G mutation: from genetics to phenotype. (Li D, et al., 2022)

Therapeutic Development for MELAS Syndrome

Drug Names	Mechanism of Action	Targets	NCT Number	Research Phase
L-arginine	Precursor for nitric oxide (NO) synthesis to improve endothelial function and cerebral perfusion	Nitric oxide synthase (NOS) in vascular endothelium	NCT01603446	Approved
L-Citrulline	Converts to L-arginine, enhancing NO production and microvascular circulation	NOS pathway	NCT03952234	Phase II/III
Dichloroacetate (DCA)	Activates pyruvate dehydrogenase (PDH) to reduce lactic acidosis by shifting metabolism to aerobic respiration	Pyruvate dehydrogenase kinase (PDK)	NCT00068913	Phase II
IW-6463	CNS-penetrant soluble guanylate cyclase (sGC) stimulator to enhance vasodilation and mitochondrial function	sGC in neurons/endothelial cells	NCT04475549	Phase II

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

Protheragen offers modern diagnostic and therapeutic development services for rare neurometabolic diseases like MELAS syndrome. We strive to advance disease models in order to elucidate the pathogenesis of MELAS syndrome, and we use innovative blood-brain barrier (BBB) models to improve the delivery and efficacy of therapeutic compounds. We strive to refine diagnostic and therapeutic strategies for MELAS syndrome by developing diagnostic kits and tailoring treatment options guided by our multi-faceted frameworks.

Therapeutic Development Services

By Molecule Types

By Mechanism of Action

Disease Model Development Services

Model Types	Model Names
In Vitro Models	Patient-Derived Cell Model Neuronal Cell Model Glial Cell Model	Co-Culture Model Brain Organoid Spinal Cord Organoid
Microfluidic Models	Neurovascular Unit Model Axon Degeneration Model Neuroinflammation Model	Neuromuscular Junction Model Synaptic Plasticity Model Organoid-on-a-Chip Model
Animal Models	MT-TL1 m.3243A>G Knock-in Mouse Model: Engineered to carry the human pathogenic m.3243A>G mutation in mitochondrial MT-TL1, recapitulating tRNA-Leu(UUR) dysfunction, progressive mitochondrial failure, and late-onset neurological deficits characteristic of MELAS syndrome. ND6 P25L Transgenic Mouse Model: Expresses a mutant ND6 subunit of mitochondrial complex I, inducing elevated ROS production and neuronal degeneration, mimicking the stroke-like episodes and metabolic crises seen in MELAS patients.

Focusing on preclinical research, Protheragen offers comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology study services to support the development and regulatory approval of potential therapies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.

References

Fan H C, Lee H F, Yue C T, et al. Clinical characteristics of mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes[J]. Life, 2021, 11(11): 1111.
Li D, Liang C, Zhang T, et al. Pathogenic mitochondrial DNA 3243A> G mutation: from genetics to phenotype[J]. Frontiers in Genetics, 2022, 13: 951185.

For research use only. Not intended for any clinical use.