ArticleEMBO molecular medicine2023
Difluoromethylornithine rebalances aberrant polyamine ratios in Snyder-Robinson syndrome.
Article in EMBO molecular medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 21 citations in OpenAlex.
- An improved Sms p.Gly56Ser model of Snyder-Robinson syndrome reveals phenotypic parallels with clinical features.Disease models & mechanisms · 2026Article
- Metabolic alterations in Snyder-Robinson syndrome lymphoblasts are ameliorated by phenylbutyrate treatment.Molecular genetics and metabolism · 2026Article
- Two lysosomal genes ATP13A2 and GBA1 interact to drive neurodegeneration.Molecular neurodegeneration · 2026Article
- Polyamine Metabolism in Brain Health and Disease.Neuropharmacology and therapy · 2026Article
- The functional roles and mechanisms of polyamines in age-related bone diseases.Cellular and molecular life sciences : CMLS · 2025Review
- Spermine synthase in Snyder-Robinson syndrome and cancer.Molecular biology reports · 2025Review
- Repurposing With Purpose: Treatment of Bachmann-Bupp Syndrome With Eflornithine and Implications for Other Polyaminopathies.American journal of medical genetics. Part C, Seminars in medical genetics · 2025Article
- Genetically encoded fluorescent reporter for polyamines.Nature communications · 2025Article
- Article
- Design, Synthesis, and Biological Activity of Novel Ornithine Decarboxylase (ODC) Inhibitors.Journal of medicinal chemistry · 2025Article
- Spermine Synthase : A Potential Prognostic Marker for Lower-Grade Gliomas.Journal of Korean Neurosurgical Society · 2025Article
- An enhanced method for the determination of polyamine content in biological samples by dansyl chloride derivatization and HPLC.Methods in enzymology · 2025Article
- Polyamine metabolism related gene index prediction of prognosis and immunotherapy response in breast cancer.Frontiers in oncology · 2025Article
- Illustrate the metabolic regulatory mechanism of Taohong Siwu decoction in ischemic stroke by mass spectrometry imaging.Analytical and bioanalytical chemistry · 2024Article
- Structural Insights into the Mechanisms Underlying Polyaminopathies.International journal of molecular sciences · 2024Review
- Impaired polyamine metabolism causes behavioral and neuroanatomical defects in a mouse model of Snyder-Robinson syndrome.Disease models & mechanisms · 2024Article
- Effects of Spermine Synthase Deficiency in Mesenchymal Stromal Cells Are Rescued by Upstream Inhibition of Ornithine Decarboxylase.International journal of molecular sciences · 2024Article
- Rebalancing polyamine levels to treat Snyder-Robinson syndrome.EMBO molecular medicine · 2023Article
- Difluoromethylornithine rebalances aberrant polyamine ratios in Snyder-Robinson syndrome.EMBO molecular medicine · 2023Article
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9 authors at 3 institutions in 2 countries.
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Abstract
Snyder-Robinson syndrome (SRS) results from mutations in spermine synthase (SMS), which converts the polyamine spermidine into spermine. Affecting primarily males, common manifestations of SRS include intellectual disability, osteoporosis, hypotonia, and seizures. Symptom management is the only treatment. Reduced SMS activity causes spermidine accumulation while spermine levels are reduced. The resulting exaggerated spermidine:spermine ratio is a biochemical hallmark of SRS that tends to correlate with symptom severity. Our studies aim to pharmacologically manipulate polyamine metabolism to correct this imbalance as a therapeutic strategy for SRS. Here we report the repurposing of 2-difluoromethylornithine (DFMO), an FDA-approved inhibitor of polyamine biosynthesis, in rebalancing spermidine:spermine ratios in SRS patient cells. Mechanistic in vitro studies demonstrate that, while reducing spermidine biosynthesis, DFMO also stimulates the conversion of spermidine into spermine in hypomorphic SMS cells and induces uptake of exogenous spermine, altogether reducing the aberrant ratios. In a Drosophila SRS model characterized by reduced lifespan, DFMO improves longevity. As nearly all SRS patient mutations are hypomorphic, these studies form a strong foundation for translational studies with significant therapeutic potential.
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