ArticleStem cell reports2021
Sonlicromanol improves neuronal network dysfunction and transcriptome changes linked to m.3243A>G heteroplasmy in iPSC-derived neurons.
Article in Stem cell reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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Who cites it
14 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025Pooled it
- Phase 2b program with sonlicromanol in patients with mitochondrial disease due to m.3243A>G mutation.Brain : a journal of neurology · 2025Trial
- An electrophysiological and proteomics roadmap for human induced glutamatergic neurons: fine-tuning of culture conditions for pathophysiological studies.Cell death discovery · 2026Article
- Neuronal branching in stem cell models of mitochondrial and neurological diseases.Stem cells (Dayton, Ohio) · 2025Review
- Automated inference of disease mechanisms in patient-hiPSC-derived neuronal networks.Communications biology · 2025Article
- Mitochondrial diseases: from molecular mechanisms to therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Peptide-mimetics derived from leucyl-tRNA synthetase are potential agents for the therapy of mt-tRNA related diseases.Frontiers in pharmacology · 2025Article
- Breaking the burst: Unveiling mechanisms behind fragmented network bursts in patient-derived neurons.Stem cell reports · 2024Article
- Clinical Approaches for Mitochondrial Diseases.Cells · 2023Review
- The Mitochondrial m.3243A>G Mutation on the Dish, Lessons from In Vitro Models.International journal of molecular sciences · 2023Review
- Mitochondrial impairment and synaptic dysfunction are associated with neurological defects in iPSCs-derived cortical neurons of MERRF patients.Journal of biomedical science · 2023Article
- An in silico and in vitro human neuronal network model reveals cellular mechanisms beyond NaStem cell reports · 2023Article
- Modeling mitochondrial DNA diseases: from base editing to pluripotent stem-cell-derived organoids.EMBO reports · 2023Review
- Boosting Mitochondrial Potential: An Imperative Therapeutic Intervention in Amyotrophic Lateral Sclerosis.Current neuropharmacology · 2023Review
Corrections and comments
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mitochondrial encephalomyopathy, lactic acidosis, and stroke-like episodes (MELAS) is often caused by an adenine to guanine variant at m.3243 (m.3243A>G) of the MT-TL1 gene. To understand how this pathogenic variant affects the nervous system, we differentiated human induced pluripotent stem cells (iPSCs) into excitatory neurons with normal (low heteroplasmy) and impaired (high heteroplasmy) mitochondrial function from MELAS patients with the m.3243A>G pathogenic variant. We combined micro-electrode array (MEA) measurements with RNA sequencing (MEA-seq) and found reduced expression of genes involved in mitochondrial respiration and presynaptic function, as well as non-cell autonomous processes in co-cultured astrocytes. Finally, we show that the clinical phase II drug sonlicromanol can improve neuronal network activity when treatment is initiated early in development. This was intricately linked with changes in the neuronal transcriptome. Overall, we provide insight in transcriptomic changes in iPSC-derived neurons with high m.3243A>G heteroplasmy, and show the pathology is partially reversible by sonlicromanol.
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Registered trials
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