ArticleCell stem cell2017
Human iPSC-Derived Neural Progenitors Are an Effective Drug Discovery Model for Neurological mtDNA Disorders.
Article in Cell stem cell, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06967831 (Using iPSC Derived Human Basal Ganglia Neurons From Patients With Leigh Syndrome for Metabolic Studies, Assay Development, and Drug Repurposing.), which is not on this map. Cited by 105 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Using iPSC Derived Human Basal Ganglia Neurons From Patients With Leigh Syndrome for Metabolic Studies, Assay Development, and Drug Repurposing.
Who cites it
105 citing papers in PubMed, 1 synthesis or guideline pooled it, 165 citations in OpenAlex.
- Modelling mitochondrial diseases in neuronsJournal of neuromuscular diseases · 2025Pooled it
- A novel multisystem approach uncovers conserved mitochondrial complex I disease phenotypes and suppressors.Research square · 2026Article
- Mitochondrial regulation of brain development: evidence from zebrafish models.Fish physiology and biochemistry · 2026Review
- Protocol for validating drug efficacy and safety in scalable 96-well platforms of human cortical organoids and melanoma brain metastases.STAR protocols · 2026Article
- Human organoids: Fit for drug discovery?Stem cell reports · 2026Review
- Linking neurogenesis, oligodendrogenesis, and myelination defects to neurodevelopmental disruption in primary mitochondrial disorders.FEBS letters · 2026Review
- Pridopidine Protects ALS Patient-Derived Neural Progenitor Cells via Sigma-1 Receptor Activation.International journal of molecular sciences · 2026Article
- Pluripotent stem-cell-based screening uncovers sildenafil as a mitochondrial disease therapy.Cell · 2026Article
- Loss of function variants in HPDL impair human cortical development via alterations of mitochondrial function.Cell death & disease · 2026Article
- Dystonia: Insights into Mechanisms and Novel Therapeutics.Current neurology and neuroscience reports · 2026Review
- Cortical organoid-derived models of the melanoma brain metastatic niche enable prioritization of cancer-targeting drugs.Cell reports methods · 2025Article
- Metabolic costs and trade-offs of hypermetabolism in human motor neurons with ATP synthase deficiency.Communications biology · 2025Article
- Expanding research and care for Leigh syndrome: efforts of a patient-led advocacy organization.Research involvement and engagement · 2025Article
- Neuronal branching in stem cell models of mitochondrial and neurological diseases.Stem cells (Dayton, Ohio) · 2025Review
- Dominant negative ATP5F1A variants disrupt oxidative phosphorylation causing neurological disorders.EMBO molecular medicine · 2025Article
- Expanding the Allelic and Clinical Heterogeneity of Movement Disorders Linked to Defects of Mitochondrial Adenosine Triphosphate Synthase.Movement disorders : official journal of the Movement Disorder Society · 2025Article
- Acoustofluidic bioassembly induced morphogenesis for therapeutic tissue fabrication.Nature communications · 2025Article
- Natural History of Patients With Mitochondrial ATPase Deficiency Due to Pathogenic Variants of MT-ATP6 and MT-ATP8.Neurology · 2025Article
- Leigh Syndrome: A Comprehensive Review of the Disease and Present and Future Treatments.Biomedicines · 2025Review
- Autism risk genes converge onbioRxiv : the preprint server for biology · 2025Article
45 more citing papers are in PubMed but not listed here.
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Authors and funding
29 authors at 9 institutions in 2 countries.
Funding
Abstract
Mitochondrial DNA (mtDNA) mutations frequently cause neurological diseases. Modeling of these defects has been difficult because of the challenges associated with engineering mtDNA. We show here that neural progenitor cells (NPCs) derived from human induced pluripotent stem cells (iPSCs) retain the parental mtDNA profile and exhibit a metabolic switch toward oxidative phosphorylation. NPCs derived in this way from patients carrying a deleterious homoplasmic mutation in the mitochondrial gene MT-ATP6 (m.9185T>C) showed defective ATP production and abnormally high mitochondrial membrane potential (MMP), plus altered calcium homeostasis, which represents a potential cause of neural impairment. High-content screening of FDA-approved drugs using the MMP phenotype highlighted avanafil, which we found was able to partially rescue the calcium defect in patient NPCs and differentiated neurons. Overall, our results show that iPSC-derived NPCs provide an effective model for drug screening to target mtDNA disorders that affect the nervous system.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.