ArticleEMBO molecular medicine2019
4'-Phosphopantetheine corrects CoA, iron, and dopamine metabolic defects in mammalian models of PKAN.
Article in EMBO molecular medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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The trial behind it
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Who cites it
50 citing papers in PubMed, 80 citations in OpenAlex.
- Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase-Associated Neurodegeneration.Movement disorders : official journal of the Movement Disorder Society · 2021Trial
- Pilot trial on the efficacy and safety of pantethine in children with pantothenate kinase-associated neurodegeneration: a single-arm, open-label study.Orphanet journal of rare diseases · 2020Trial
- Therapeutic Advances in Major NBIA Disorders: Current Strategies and Translational Challenges.Neurology international · 2026Review
- Precision Medicine in Neurodegeneration with Brain Iron Accumulation (NBIA) Disorders: An Update on Emerging Treatments.Movement disorders clinical practice · 2026Review
- Coenzyme A mitigates cystine-deprivation-induced ferroptosis by suppressing the iron-starvation response.The FEBS journal · 2026Article
- TheScience advances · 2026Article
- Case Report: clinical manifestations and imaging features associated with PANK2 c.940C>T variant in PKAN with symmetric basal ganglia calcification.Frontiers in genetics · 2026Article
- Coenzyme A in Brain Biology and Neurodegeneration.Biomedicines · 2025Review
- Iron Dysregulation in Neurodegeneration with Brain Iron Accumulation (NBIA): Links between Mutations Occurring in BPAN, PKAN, MPAN and PLAN Types and Iron Metabolism.Molecular neurobiology · 2025Review
- Mitigating the impact of study-start delays in clinical trials for rare disorders: insights and lessons from a PKAN trial.Orphanet journal of rare diseases · 2025Article
- Coenzyme A protects against ferroptosis via CoAlation of mitochondrial thioredoxin reductase.The Journal of clinical investigation · 2025Article
- Pantethine ameliorates dilated cardiomyopathy features in PPCS deficiency disorder in patients and cell line models.Communications medicine · 2025Article
- Characterization of the Pank2-/- mouse retinal phenotype as a pre-clinical model for pantothenate kinase-associated neurodegeneration.PloS one · 2025Article
- RareBrain communications · 2025Article
- In-Gel Activity Assay of Mammalian Mitochondrial and Cytosolic Aconitases, Surrogate Markers of Compartment-Specific Oxidative Stress and Iron Status.Bio-protocol · 2024Article
- Coenzyme A biosynthesis: mechanisms of regulation, function and disease.Nature metabolism · 2024Review
- Patient-Derived Cellular Models for Polytarget Precision Medicine in Pantothenate Kinase-Associated Neurodegeneration.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Drug Drop Test: How to Quickly Identify Potential Therapeutic Compounds for Mitochondrial Diseases Using YeastInternational journal of molecular sciences · 2023Review
- Alpha-lipoic acid supplementation corrects pathological alterations in cellular models of pantothenate kinase-associated neurodegeneration with residual PANK2 expression levels.Orphanet journal of rare diseases · 2023Article
- Inherited Disorders of Coenzyme A Biosynthesis: Models, Mechanisms, and Treatments.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
23 authors at 2 institutions in 2 countries.
Funding
Abstract
Pantothenate kinase-associated neurodegeneration (PKAN) is an inborn error of CoA metabolism causing dystonia, parkinsonism, and brain iron accumulation. Lack of a good mammalian model has impeded studies of pathogenesis and development of rational therapeutics. We took a new approach to investigating an existing mouse mutant of Pank2 and found that isolating the disease-vulnerable brain revealed regional perturbations in CoA metabolism, iron homeostasis, and dopamine metabolism and functional defects in complex I and pyruvate dehydrogenase. Feeding mice a CoA pathway intermediate, 4'-phosphopantetheine, normalized levels of the CoA-, iron-, and dopamine-related biomarkers as well as activities of mitochondrial enzymes. Human cell changes also were recovered by 4'-phosphopantetheine. We can mechanistically link a defect in CoA metabolism to these secondary effects via the activation of mitochondrial acyl carrier protein, which is essential to oxidative phosphorylation, iron-sulfur cluster biogenesis, and mitochondrial fatty acid synthesis. We demonstrate the fidelity of our model in recapitulating features of the human disease. Moreover, we identify pharmacodynamic biomarkers, provide insights into disease pathogenesis, and offer evidence for 4'-phosphopantetheine as a candidate therapeutic for PKAN.
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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.