ArticleJCI insight2021
Efficacy of AAV9-mediated SGPL1 gene transfer in a mouse model of S1P lyase insufficiency syndrome.
Article in JCI insight, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 24 papers, 1 of them a synthesis that pooled it.
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.
Sphingosine Phosphate Lyase Insufficiency Syndrome - Observational Study and Patient Registry (International)
Natural History and Phenotypic Spectrum of Sphingosine Phosphate Lyase Insufficiency Syndrome (SPLIS)
Who cites it
24 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Sphingosine phosphate lyase insufficiency syndrome: a systematic review.World journal of pediatrics : WJP · 2023Pooled it
- Gene-disease relationships for glomerular phenotypes: expert recommendations from ClinGen.Nature reviews. Nephrology · 2026Review
- New therapeutic hope for rare podocytopathies.Pediatric nephrology (Berlin, Germany) · 2026Article
- Redirection of sphingolipid metabolism drives cytoskeletal defects in SPLIS and reveals ROCK inhibition as therapy.The Journal of clinical investigation · 2026Article
- Advances in SRNS Gene Research: From Precision Classification to Precision Diagnosis and Treatment.Biomedicines · 2026Review
- Podocyte specific exon skipping after disease onset improves kidney pathology and function in a mouse model of Alport syndrome.Scientific reports · 2025Article
- Clinical presentation and management challenges of sphingosine-1-phosphate lyase insufficiency syndrome associated with an SGPL1 variant: a case report.BMC pediatrics · 2025Article
- Phenotypic quantification of Nphs1-deficient mice.Journal of nephrology · 2025Article
- Gene Editing: An Effective Tool for the Future Treatment of Kidney Disease.Journal of inflammation research · 2025Review
- Sphingosine phosphate lyase insufficiency syndrome as a primary immunodeficiency state.Advances in biological regulation · 2024Review
- Factors influencing survival in sphingosine phosphate lyase insufficiency syndrome: a retrospective cross-sectional natural history study of 76 patients.Orphanet journal of rare diseases · 2024Article
- Quantifiable and reproducible phenotypic assessment of a constitutive knockout mouse model for congenital nephrotic syndrome of the Finnish type.Scientific reports · 2024Article
- BDNF Modulation by microRNAs: An Update on theCells · 2024Review
- Gene therapy with AAV9-SGPL1 in an animal model of lung fibrosis.The Journal of pathology · 2024Article
- Prevalence estimate of sphingosine phosphate lyase insufficiency syndrome in worldwide and select populations.Genetics in medicine open · 2024Article
- AAV-SPL 2.0, a Modified Adeno-Associated Virus Gene Therapy Agent for the Treatment of Sphingosine Phosphate Lyase Insufficiency Syndrome.International journal of molecular sciences · 2023Article
- Recent Advances in Proteinuric Kidney Disease/Nephrotic Syndrome: Lessons from Knockout/Transgenic Mouse Models.Biomedicines · 2023Review
- A retrospective analysis of endocrine disease in sphingosine-1-phosphate lyase insufficiency: case series and literature review.Endocrine connections · 2022Review
- Sphingosine Phosphate Lyase Is Upregulated in Duchenne Muscular Dystrophy, and Its Inhibition Early in Life Attenuates Inflammation and Dystrophy in Mdx Mice.International journal of molecular sciences · 2022Article
- Neurological Consequences of Sphingosine Phosphate Lyase Insufficiency.Frontiers in cellular neuroscience · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
15 authors.
Funding
Abstract
Sphingosine-1-phosphate lyase insufficiency syndrome (SPLIS) is a rare metabolic disorder caused by inactivating mutations in sphingosine-1-phosphate lyase 1 (SGPL1), which is required for the final step of sphingolipid metabolism. SPLIS features include steroid-resistant nephrotic syndrome and impairment of neurological, endocrine, and hematopoietic systems. Many affected individuals die within the first 2 years. No targeted therapy for SPLIS is available. We hypothesized that SGPL1 gene replacement would address the root cause of SPLIS, thereby serving as a universal treatment for the condition. As proof of concept, we evaluated the efficacy of adeno-associated virus 9-mediated transfer of human SGPL1 (AAV-SPL) given to newborn Sgpl1-KO mice that model SPLIS and die in the first weeks of life. Treatment dramatically prolonged survival and prevented nephrosis, neurodevelopmental delay, anemia, and hypercholesterolemia. STAT3 pathway activation and elevated proinflammatory and profibrogenic cytokines observed in KO kidneys were attenuated by treatment. Plasma and tissue sphingolipids were reduced in treated compared with untreated KO pups. SGPL1 expression and activity were measurable for at least 40 weeks. In summary, early AAV-SPL treatment prevents nephrosis, lipidosis, and neurological impairment in a mouse model of SPLIS. Our results suggest that SGPL1 gene replacement holds promise as a durable and universal targeted treatment for SPLIS.
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What Socratic 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 Socratic graph.