DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephrotic syndrome, type 22 — screening already-approved drugs against its 1-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNephrotic syndrome, type 22 maps to a 1-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 nephrotic syndrome, type 22 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.
What the evidence adds up to
Steroid-resistant nephrotic syndrome (SRNS) is the second most common cause of chronic kidney disease in the first three decades of life, manifests histologically as focal segmental glomerulosclerosis (FSGS), and carries a 33% risk of relapse after renal transplant. No efficient treatment exists. In approximately 30% of individuals who develop SRNS before age 25, a causative mutation can be found in one of more than 30 known genes. Mutation analysis is recommended for these patients because it may uncover a form of SRNS amenable to treatment, such as coenzyme Q10, and may permit personalised treatment based on genetic causation.
In a 2010 study of 148 unrelated Spanish patients with SRNS, compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for the p.R229Q variant and one pathogenic mutation, mostly p.A284V. Patients carrying this specific NPHS2 allele combination did not respond to corticosteroids or immunosuppressors, showed FSGS, an average 8-year progression to end-stage renal disease, and a low risk for recurrence of FSGS after kidney transplant. The p.R229Q variant was more frequent among SRNS cases than controls (odds ratio 2.65; P=0.02).
For children with idiopathic nephrotic syndrome who are younger than 4 years, a 2021 randomised controlled trial of 172 patients compared 3 months versus 6 months of initial prednisone therapy. After 2 years of follow-up, the proportions of patients in sustained remission and with frequent relapses at 1 and 2 years were similar between groups. The hazard ratio for time to relapse was 0.75 (95% CI 0.53–1.06) and for frequent relapses was 0.78 (95% CI 0.52–1.18). Rates of adverse events were similar. The authors concluded that prolonged initial prednisolone therapy does not significantly alter the disease course in young children with nephrotic syndrome.
What remains missing is a treatment that reliably alters the course of steroid-resistant disease, particularly in patients with identified genetic causes. The 2021 trial shows that even in steroid-sensitive young children, extending initial corticosteroid therapy does not change long-term outcomes. For the subset of patients with monogenic SRNS, no targeted therapies beyond coenzyme Q10 for specific defects have been tested in controlled trials. Funding for genotype-stratified trials, better patient stratification by genetic cause, and development of drugs targeting podocyte pathways identified by the known genes are still lacking.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Genetic testing in steroid-resistant nephrotic syndrome: when and how?
AbstractSteroid-resistant nephrotic syndrome (SRNS) represents the second most frequent cause of chronic kidney disease in the first three decades of life. It manifests histologically as focal segmental glomerulosclerosis (FSGS) and carries a 33% risk of relapse in a renal transplant. No efficient treatment exists. Identification of single-gene (monogenic) causes of SRNS has moved the glomerular epithelial cell (podocyte) to the center of its pathogenesis. Recently, mutations in >30 recessive or dominant genes were identified as causing monogenic forms of SRNS, thereby revealing the encoded proteins as essential for glomerular function. These findings helped define protein interaction complexes and functional pathways that could be targeted for treatment of SRNS. Very recently, it was discovered that in the surprisingly high fraction of ∼30% of all individuals who manifest with SRNS before 25 years of age, a causative mutation can be detected in one of the ∼30 different SRNS-causing genes. These findings revealed that SRNS and FSGS are not single disease entities but rather are part of a spectrum of distinct diseases with an identifiable genetic etiology. Mutation analysis should be offered to all individuals who manifest with SRNS before the age of 25 years, because (i) it will provide the patient and families with an unequivocal cause-based diagnosis, (ii) it may uncover a form of SRNS that is amenable to treatment (e.g. coenzyme Q10), (iii) it may allow avoidance of a renal biopsy procedure, (iv) it will further unravel the puzzle of pathogenic pathways of SRNS and (v) it will permit personalized treatment options for SRNS, based on genetic causation in way of ‘precision medicine’.
Clinical Journal of the American Society of Nephrology · 2010 · 77 citations · open access
Clinical Value of NPHS2 Analysis in Early- and Adult-Onset Steroid-Resistant Nephrotic Syndrome
AbstractBACKGROUND AND OBJECTIVES: To date, very few cases with adult-onset focal segmental glomerulosclerosis (FSGS) carrying NPHS2 variants have been described, all of them being compound heterozygous for the p.R229Q variant and one pathogenic mutation. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: Mutation analysis was performed in 148 unrelated Spanish patients, of whom 50 presented with FSGS after 18 years of age. Pathogenicity of amino acid substitutions was evaluated through an in silico scoring system. Haplotype analysis was carried out using NPHS2 single nucleotide polymorphism and microsatellite markers. RESULTS: Compound heterozygous or homozygous NPHS2 pathogenic mutations were identified in seven childhood-onset steroid-resistant nephrotic syndrome (SRNS) cases. Six additional cases with late childhood- and adult-onset SRNS were compound heterozygotes for p.R229Q and one pathogenic mutation, mostly p.A284V. p.R229Q was more frequent among SRNS cases relative to controls (odds ratio=2.65; P=0.02). Significantly higher age at onset of the disease and slower progression to ESRD were found in patients with one pathogenic mutation plus the p.R229Q variant in respect to patients with two NPHS2 pathogenic mutations. CONCLUSIONS: NPHS2 analysis has a clinical value in both childhood- and adult-onset SRNS patients. For adult-onset patients, the first step should be screening for p.R229Q and, if positive, for p.A284V. These alleles are present in conserved haplotypes, suggesting a common origin for these substitutions. Patients carrying this specific NPHS2 allele combination did not respond to corticoids or immunosuppressors and showed FSGS, average 8-year progression to ESRD, and low risk for recurrence of FSGS after kidney transplant.
Journal of the American Society of Nephrology · 2021 · 1 citations
Randomized Controlled Trial Comparing 3- vs. 6-Months Initial Prednisone Therapy in Young (<4-Year-Old) Children with Nephrotic Syndrome
AbstractBackground: While recent RCTs suggest no role for prolonged (>2-3 months) initial corticosteroid therapy in NS, subgroup analysis in 2-studies suggests its association with reduced frequency of subsequent relapses in children <4-6 yr-old. This multicenter open-label trial examines the efficacy & safety of 3-months versus 6-months prednisone therapy during the first episode of NS in patients <4-yr-old [CTRI2015/06/005939; NCT03141970]. Methods: Following ethics approval & parental consent, 172 consecutive patients (1-4 yr-old) were enrolled at onset of idiopathic NS during 2015-19. After 6-wk daily & 6-wk alternate day (AD) initial prednisone therapy, they were randomized (1:1) to either tapering prednisone on AD for 12-wk or no therapy. Relapses were treated with prednisone 2 mg/kg/d till remission, then on AD for 4-wk. Outcomes, based on intention-to-treat analysis during 2-yr follow up, include the proportion of patients with relapse or frequent relapses, time to first relapse, cumulative steroid dose & adverse effects. Based on a prior RCT, at 80% power & α=0.05) 78 patients were required per group to show 30% higher sustained remission with 6-mo therapy. Results: Baseline features in the groups were similar (Fig 1). Despite trends favoring 6-mo therapy, proportions of patients in sustained remission & frequent relapses at 1- & 2-yr, time to relapse (HR 0.75; 95%CI 0.53-1.06) or frequent relapses (HR 0.78; 0.52-1.18), and relapse rates were similar (Fig 1, 2). The rates of adverse events were similar.Fig 1.: Baseline characteristics & key outcome variablesConclusions: Prolonged initial prednisolone therapy does not significantly alter the disease course in young children with NS. Funding: Government Support - Non-U.S.Fig 2.: Kaplan-Meier estimates of the time to (a) relapse, and (b) frequent relapses
International Journal of Science and Healthcare Research · 2024 · 0 citations · open access
Impact of Corticosteroid Therapy on Children with Nephrotic Syndrome
AbstractNephrotic syndrome is a condition that causes the kidneys to leak large amounts of protein into the urine. This can lead to a range of problems, including swelling of body tissues and a greater chance of catching infections. Although nephrotic syndrome can affect people of any age, it's usually first diagnosed in children aged between 1 and 6 years old. It tends to be more common in those with an Asian background although the reason is unknown. Keywords: Nephrotic Syndrome, Corticosteroid, Ocular complications, Bone mineral density, obesity.
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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