DeCure for Congenital nephrotic syndrome, Finnish type
DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for congenital nephrotic syndrome, Finnish type — screening already-approved drugs against its 7-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleCongenital nephrotic syndrome, Finnish type maps to a 7-gene Open Targets module — the target space DeCure's AI scientist screens approved drugs against.
DeCure.ai methodSignature reversal (LINCS) plus network proximity (STRING) rank already-approved drugs likely to perturb this module — the same engine that produces DeCure.ai's repurposing hypotheses.
Repurposing thesisScreening approved medicines against this disease module, then publishing the evidence for the strongest candidate. Known pharmacology and human exposure data make the first question sharper — they do not establish safety or efficacy in a new indication.
Research record
01
ResearchComing soon
Candidate research + dossier — target rationale, drug-repurposing thesis and evidence pack.proof: Published dossier + on-chain hash
02
ValidationComing soon
In-vitro biological validation at a contract research org (CRO).proof: CRO contract + in-vitro report
03
Peer review & paperComing soon
Peer-reviewed paper published open-access (preprint + journal).proof: DOI + open-access link + on-chain hash
Current lead
No approved-drug candidate for congenital nephrotic syndrome, finnish type is corroborated in the literature DeepSearch retrieved. Some conditions are managed with non-pharmacological care — a device, surgery or physical therapy — rather than a medicine; that may be the case here, or the literature we found may simply be too sparse yet to support a drug-repurposing angle.
Molecular view
phospholipase C epsilon 1 (PLCE1) — PLCE1 is one of the genes genetically linked to this disease in Open Targets — shown as context, not as a drug target we're pursuing: no approved-drug candidate for this disease is yet corroborated in the literature we found.
Loading structure…
helix sheet gtpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2C5L · 1.9 Å · ligand GUANOSINE-5'-TRIPHOSPHATE (GTP). Experimental structure, not a prediction.
What the evidence adds up to
Congenital nephrotic syndrome of the Finnish type is an autosomal recessive disease caused by mutations in the NPHS1 gene, which encodes nephrin, a key component of the podocyte slit diaphragm. In the Finnish population, two nonsense mutations account for over 94% of all mutations. Outside Finland, the mutation spectrum is broader and includes missense, nonsense, splice site, deletion, and insertion mutations; a 2001 update reported 30 known mutations worldwide and described 20 novel ones. A 2008 case from Serbia identified a homozygous 614del8ins2TT mutation in a neonate who died despite substitution, antiproteinuric, and antithrombotic therapy; prenatal testing in a subsequent pregnancy revealed heterozygosity, meaning the foetus was a carrier.
The disease presents with massive proteinuria, hypoalbuminaemia, and oedema within the first three months of life. It is resistant to corticosteroids and immunosuppressive therapy. A 2013 review states that the clinical course is a continuous worsening to end-stage renal failure, and that renal transplantation is the best therapeutic option. A 2024 case report describes a non-Finnish three-year-old girl whose congenital nephrotic syndrome was initially misdiagnosed as minimal change disease; standard treatments with cyclosporine and steroids had no effect. Genetic testing and kidney biopsy confirmed Finnish-type nephrotic syndrome, and she was treated with protein-sparing drugs to reduce oedema while awaiting a kidney transplant.
One abstract from 1999, despite its title mentioning congenital nephrotic syndrome of the Finnish type in Irish families, actually reports on childhood dairy and calcium consumption and adult cardiovascular mortality in England and Scotland. It found no strong evidence linking childhood dairy intake to coronary heart disease or stroke mortality, though childhood calcium intake was inversely associated with stroke mortality (hazard ratio 0.41, 95% CI 0.16 to 1.05, p for trend 0.04). All-cause mortality was lowest in those with the highest family dairy (HR 0.77, 95% CI 0.61 to 0.98) and calcium intake (HR 0.77, 95% CI 0.60 to 0.98). This abstract is not about congenital nephrotic syndrome and provides no data on that disease.
What is still missing is a therapy that alters the underlying disease course; current management relies on renal transplantation. No drug has been shown to reverse or halt the nephrin defect. The available evidence consists of case reports and mutation surveys; there are no controlled trials. Patient stratification by specific NPHS1 mutation type may be relevant, but no genotype-directed treatment exists. Funding for systematic natural history studies and for developing therapies that target the podocyte slit diaphragm remains absent.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Human Mutation · 2001 · 192 citations
Mutation spectrum in the nephrin gene (NPHS1) in congenital nephrotic syndrome
AbstractCongenital nephrotic syndrome, Finnish type (CNF or NPHS1), is an autosomal recessive disease characterized by massive proteinuria and development of nephrotic syndrome shortly after birth. The disease is most common in Finland, but many patients have been identified in other populations. The disease is caused by mutations in the gene for nephrin which is a key component of the glomerual ultrafilter, the podocyte slit diaphragm. A total of 30 mutations have been reported in the nephrin gene in patients with congenital nephrotic syndrome worldwide. In the Finnish population, two main mutations have been found. These two nonsense mutations account for over 94% of all mutations in Finland. Most mutations found in non-Finnish patients are missense mutations, but they include also nonsense and splice site mutations, as well as deletions and insertions. This mutation update summarizes the nature of all previously reported nephrin mutations and, additionally, describes 20 novel mutations recently identified in our laboratory.
Archives of Disease in Childhood · 1999 · 37 citations · open access
Improved prognosis for congenital nephrotic syndrome of the Finnish type in Irish families
Abstract<h3>Background:</h3> Dairy consumption in childhood may have long-term effects on cardiovascular mortality through influencing the development of risk factors or programming effects. <h3>Objective:</h3> To investigate whether dairy and calcium consumption in childhood is associated with adult mortality due to coronary heart disease (CHD), stroke and all causes. <h3>Methods:</h3> In 1937–9, 4999 children in England and Scotland participated in a study of family food consumption, assessed from 7-day household food inventories. Cause of death was ascertained between 1948 and 2005 in 4374 traced cohort members with complete data. Per capita household intake estimates for dairy products and calcium were used as proxies for individual intake. <h3>Results:</h3> No strong evidence that a family diet in childhood high in dairy products was associated with CHD or stroke mortality was found. However, childhood calcium intake was inversely associated with stroke mortality (multivariable adjusted hazard ratio (HR) for highest versus lowest calcium group: 0.41; 95% confidence interval (CI) 0.16 to 1.05; p for trend = 0.04), but not CHD mortality. All-cause mortality was lowest in those with the highest family dairy (HR = 0.77; 95% CI 0.61 to 0.98; p for trend = 0.04) and calcium intake (HR = 0.77, 95% CI 0.60 to 0.98; p for trend = 0.05). <h3>Conclusions:</h3> Children whose family diet in the 1930s was high in calcium were at reduced risk of death from stroke. Furthermore, childhood diets rich in dairy or calcium were associated with lower all-cause mortality in adulthood. Replication in other study populations is needed to determine whether residual confounding explains part of these findings.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
Early diagnosis and management of finish type congenital nephrotic syndrome in a 3-year-old child: A case report
AbstractThis study describes a 3-year-old non Finnish girl who was diagnosed with Finnish-type nephrotic syndrome (FTNS), a rare kidney illness brought on by NPHS1 gene abnormalities. Even though she had low protein levels and severe swelling when she was three months old, her case of congenital nephrotic syndrome (CNS) was incorrectly identified as minimal change disease (MCD). The standard MCD treatments, cyclosporine and steroids, did not affect her. A genetic test and a kidney sample confirmed the diagnosis of FTNS, a condition that necessitates an early renal transplant for survival. She is awaiting a kidney transplant and was treated with drugs that save proteins to lessen her edema. The study emphasizes the significance of FTNS early and correct diagnosis as well as the requirement for alternate treatments for this difficult illness.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
Early diagnosis and management of finish type congenital nephrotic syndrome in a 3-year-old child: A case report
AbstractThis study describes a 3-year-old non Finnish girl who was diagnosed with Finnish-type nephrotic syndrome (FTNS), a rare kidney illness brought on by NPHS1 gene abnormalities. Even though she had low protein levels and severe swelling when she was three months old, her case of congenital nephrotic syndrome (CNS) was incorrectly identified as minimal change disease (MCD). The standard MCD treatments, cyclosporine and steroids, did not affect her. A genetic test and a kidney sample confirmed the diagnosis of FTNS, a condition that necessitates an early renal transplant for survival. She is awaiting a kidney transplant and was treated with drugs that save proteins to lessen her edema. The study emphasizes the significance of FTNS early and correct diagnosis as well as the requirement for alternate treatments for this difficult illness.
Open Repository of the University of Porto (University of Porto) · 2013 · 0 citations · open access
Síndrome nefrótico no 1º ano de vida
AbstractThere were identified several mutations in the genes that encode the proteins of the glomerular filtration barrier, associated with the Nephrotic Syndrome in the first year of life. The NPHS1 gene, which encodes the nephrin protein, is mutated in Congenital Nephrotic Syndrome of the Finnish type. This disease usually presents with edema, massive proteinuria and hypoalbuminaemia during the first 3 months of life and is resistant to corticosteroids and immunosuppressive therapy. This syndrome is inherited in an autosomal recessive mode. The clinical course is a continuous worsening to end stage renal failure. Renal transplantation presents itself as the best therapeutic option for these children. The case reported is about a 6 year old boy, submitted to renal transplant with a kidney of a cadaveric donor. He developed a Nephrotic Syndrome classified as Sindrome Nefrotico no 1o ano de vida 7 Congenital Nephrotic Syndrome of the Finnish type, associated with a new mutation in NPHS1, never described before. Based on this case, it is presented a review of the Congenital Nephrotic Syndrome, natural history, treatment options and prognosis.
Srpski arhiv za celokupno lekarstvo · 2008 · 0 citations · open access
Congenital nephrotic syndrome
AbstractINTRODUCTION: Congenital nephrotic syndrome is usually presented with heavy proteinuria, hypoproteinaemia, oedema and hyperlipidaemia in a child from its birth until the age of 3 months. Aetiology of the disease is mutation in the relevant gene or it develops secondary to various infections. The most common form of congenital nephrotic syndrome is caused by mutation in gene for nephrin, the most important protein of the slit diaphragm. CASE OUTLINE: We present the patient with the clinical and laboratory signs of nephrotic syndrome expressed in the first day of life. Despite the adequate and regular substitution, antiproteinuric and antithrombotic therapy, complications occurred and the patient deceased. Genetic analysis revealed homozygous mutation in gene for nephrin (614del8ins2TT). Three years later, in the patient's mother who was in the 12th week of pregnancy at that time, biopsy of chorionic villi was performed and the foetal genetic material showed heterozygosity for the same recessive mutation which meant that the foetus had the status of a carrier. To the best of our knowledge, this is the first family in Serbia in which prenatal molecular--genetic testing for the congenital nephrotic syndrome was accomplished. CONCLUSION: We wish to stress the importance of molecular diagnosis in patients with congenital nephrotic syndrome in order to perform early prenatal diagnosis in future pregnancies.
Finnish Type Congenital Nephrotic Syndrome With Exon Sequencing Confirmation in Taiwan: A Case Report
AbstractCongenital nephrotic syndrome Finnish type (CNF) is a rare and severe kidney disorder starting soon after birth, characterized by premature birth, a small size for gestational age, and an enlarged placenta. Early-onset nephrosis with heavy proteinuria, hyperlipidemia, hypercoagulopathy, and an immunocompromised status often causes poor growth and early mortality if not treated promptly. The current treatment strategy of parenteral albumin supplementation, a hyper-caloric and protein-abundant diet, and medications to prevent and treat complications has improved patient outcomes by making curative renal transplantation possible. This report describes a female newborn diagnosed with CNF incidentally before the onset of symptoms. To the best of our knowledge, she was the first CNF case with a diagnosis confirmed by genetic testing (whole-exon sequencing) in Taiwan.
Disease module: DeepOracle (Open Targets). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works (targeted per-candidate search), resolved on OpenAlex.
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