ArticlePloS one2018
Fosmetpantotenate (RE-024), a phosphopantothenate replacement therapy for pantothenate kinase-associated neurodegeneration: Mechanism of action and efficacy in nonclinical models.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
20 citing papers in PubMed, 26 citations in OpenAlex.
- Fosmetpantotenate Randomized Controlled Trial in Pantothenate Kinase-Associated Neurodegeneration.Movement disorders : official journal of the Movement Disorder Society · 2021Trial
- Precision metabolic therapy for propionic acidemia.Biochemical pharmacology · 2026Review
- Precision Medicine in Neurodegeneration with Brain Iron Accumulation (NBIA) Disorders: An Update on Emerging Treatments.Movement disorders clinical practice · 2026Review
- Metabolomic and proteomic applications to exercise biomedicine.Translational exercise biomedicine · 2024Review
- Inherited Disorders of Coenzyme A Biosynthesis: Models, Mechanisms, and Treatments.International journal of molecular sciences · 2023Review
- Probing coenzyme A homeostasis with semisynthetic biosensors.Nature chemical biology · 2023Article
- Comparative Pharmacology of a Bis-Pivaloyloxymethyl Phosphonate Prodrug Inhibitor of Enolase after Oral and Parenteral Administration.ACS pharmacology & translational science · 2023Article
- Prodrugs of a 1-Hydroxy-2-oxopiperidin-3-yl Phosphonate Enolase Inhibitor for the Treatment ofJournal of medicinal chemistry · 2022Article
- Bi-Allelic Mutations in ZebrafishInternational journal of molecular sciences · 2022Article
- Pantothenate kinase 2 interacts with PINK1 to regulate mitochondrial quality control via acetyl-CoA metabolism.Nature communications · 2022Article
- Coenzyme a Biochemistry: From Neurodevelopment to Neurodegeneration.Brain sciences · 2021Review
- Towards Precision Therapies for Inherited Disorders of Neurodegeneration with Brain Iron Accumulation.Tremor and other hyperkinetic movements (New York, N.Y.) · 2021Review
- Emerging Disease-Modifying Therapies in Neurodegeneration With Brain Iron Accumulation (NBIA) Disorders.Frontiers in neurology · 2021Review
- Turnover rate of coenzyme A in mouse brain and liver.PloS one · 2021Article
- B Vitamins and Fatty Acids: What Do They Share with Small Vessel Disease-Related Dementia?International journal of molecular sciences · 2019Review
- The FOsmetpantotenate Replacement Therapy (FORT) randomized, double-blind, Placebo-controlled pivotal trial: Study design and development methodology of a novel primary efficacy outcome in patients with pantothenate kinase-associated neurodegeneration.Clinical trials (London, England) · 2019Article
- Improved Selective Class I HDAC and Novel Selective HDAC3 Inhibitors: Beyond Hydroxamic Acids and Benzamides.ACS medicinal chemistry letters · 2019Article
- Levodopa-induced dyskinesias in mitochondrial membrane protein-associated neurodegeneration.Neurology. Clinical practice · 2019Article
- The ProTide Prodrug Technology: Where Next?ACS medicinal chemistry letters · 2019Article
- Proposed Therapies for Pantothenate-Kinase-Associated Neurodegeneration.Journal of experimental neuroscience · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
In cells, phosphorylation of pantothenic acid to generate phosphopantothenic acid by the pantothenate kinase enzymes is the first step in coenzyme A synthesis. Pantothenate kinase 2, the isoform localized in neuronal cell mitochondria, is dysfunctional in patients with pantothenate kinase-associated neurodegeneration. Fosmetpantotenate is a phosphopantothenic acid prodrug in clinical development for treatment of pantothenate kinase-associated neurodegeneration, which aims to replenish phosphopantothenic acid in patients. Fosmetpantotenate restored coenzyme A in short-hairpin RNA pantothenate kinase 2 gene-silenced neuroblastoma cells and was permeable in a blood-brain barrier model. The rate of fosmetpantotenate metabolism in blood is species-dependent. Following up to 700 mg/kg orally, blood exposure to fosmetpantotenate was negligible in rat and mouse, but measurable in monkey. Consistent with the difference in whole blood half-life, fosmetpantotenate dosed orally was found in the brains of the monkey (striatal dialysate) but was absent in mice. Following administration of isotopically labeled-fosmetpantotenate to mice, ~40% of liver coenzyme A (after 500 mg/kg orally) and ~50% of brain coenzyme A (after 125 μg intrastriatally) originated from isotopically labeled-fosmetpantotenate. Additionally, 10-day dosing of isotopically labeled-fosmetpantotenate, 12.5 μg, intracerebroventricularly in mice led to ~30% of brain coenzyme A containing the stable isotopic labels. This work supports the hypothesis that fosmetpantotenate acts to replace reduced phosphopantothenic acid in pantothenate kinase 2-deficient tissues.
Indexed as
Identifiers
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.