DeCure for Familial steroid-resistant nephrotic syndrome with sensorineural deafness
DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for familial steroid-resistant nephrotic syndrome with sensorineural deafness — screening already-approved drugs against its 2-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial steroid-resistant nephrotic syndrome with sensorineural deafness maps to a 2-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 familial steroid-resistant nephrotic syndrome with sensorineural deafness 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
In a 2014 study of 31 children with sporadic steroid-resistant nephrotic syndrome (no family history, no congenital onset, no extrarenal symptoms at presentation), a custom next-generation sequencing panel of 19 nephrotic-syndrome genes found a genetic alteration in 32.3% of the steroid-resistant group and in zero of 38 steroid-sensitive controls. Among the steroid-resistant children, none of those with a detected alteration responded to immunosuppressive agents, whereas 57.9% of those without an alteration did respond. Age at onset and kidney biopsy findings did not differ between the two steroid-resistant subgroups.
The 2001 case report describes a six-year-old boy who presented with steroid-unresponsive nephrotic syndrome and was found to have focal segmental glomerulosclerosis, hypoparathyroidism, and sensorineural deafness. He progressed to end-stage renal failure, received dialysis and a cadaveric kidney transplant, and later developed progressive neurological deterioration diagnosed as mitochondrial myopathy and neuropathy. This single case links sensorineural deafness and steroid resistance to a mitochondrial cytopathy, but no genetic confirmation is reported.
Two review articles from 2013 and 2017 summarise the growing list of genes associated with steroid-resistant nephrotic syndrome and note that genetic findings correlate with poor response to immunosuppression and low risk of post-transplant recurrence. Neither review provides new trial data or treatment recommendations.
What remains missing is a prospective trial that stratifies patients by genotype before assigning therapy, funding for such a trial, and a validated method to distinguish mitochondrial from nuclear genetic causes in the clinic without relying on late neurological signs.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Journal of the American Society of Nephrology · 2014 · 97 citations · open access
Heterogeneous Genetic Alterations in Sporadic Nephrotic Syndrome Associate with Resistance to Immunosuppression
AbstractIn children, sporadic nephrotic syndrome can be related to a genetic cause, but to what extent genetic alterations associate with resistance to immunosuppression is unknown. In this study, we designed a custom array for next-generation sequencing analysis of 19 target genes, reported as possible causes of nephrotic syndrome, in a cohort of 31 children affected by sporadic steroid-resistant nephrotic syndrome and 38 patients who exhibited a similar but steroid-sensitive clinical phenotype. Patients who exhibited extrarenal symptoms, had a familial history of the disease or consanguinity, or had a congenital onset were excluded. We identified a genetic cause in 32.3% of the children with steroid-resistant disease but zero of 38 children with steroid-sensitive disease. Genetic alterations also associated with lack of response to immunosuppressive agents in children with steroid-resistant disease (0% of patients with alterations versus 57.9% of patients without alterations responded to immunosuppressive agents), whereas clinical features, age at onset, and pathologic findings were similar in steroid-resistant patients with and without alterations. These results suggest that heterogeneous genetic alterations in children with sporadic forms of nephrotic syndrome associate with resistance to steroids as well as immunosuppressive treatments. In these patients, a comprehensive screening using such an array may, thus, be useful for genetic counseling and may help clinical decision making in a fast and cost-efficient manner.
Pediatric Health Medicine and Therapeutics · 2017 · 68 citations · open access
Steroid-resistant nephrotic syndrome: past and current perspectives
AbstractPatients with steroid-resistant nephrotic syndrome (SRNS) represent a challenging subset of patients with nephrotic syndrome who often fail standard immunosuppression and have a higher likelihood of progressing to end-stage renal disease. Appropriate treatment of SRNS requires an adequate understanding of the historical treatment, renal histopathology, and genetics associated with the disease. The aim of this review is to present a comprehensive appraisal of the history, role of renal biopsy, genetics, and treatment of SRNS.
Genetics of steroid‐resistant nephrotic syndrome: a review of mutation spectrum and suggested approach for genetic testing
AbstractUNLABELLED: Identification of genes, associated mutations and genotype-phenotype correlations in steroid-resistant nephrotic syndrome (SRNS) is being translated to clinical practice through genetic testing. This review provides an update on the genes and mutations associated with SRNS along with a suggested approach for genetic testing in patients with SRNS. CONCLUSION: The number of indentified genes associated with SRNS is increasing along with our understanding of their impact on treatment response and risk of recurrence. A systematic approach to genetic testing in patients with SRNS might aid the physician in selecting appropriate treatment.
Postgraduate Medical Journal · 2001 · 25 citations · open access
Mitochondrial cytopathy presenting with focal segmental glomerulosclerosis, hypoparathyroidism, sensorineural deafness, and progressive neurological disease
AbstractA 6 year old boy who presented with steroid unresponsive nephrotic syndrome is reported. He was found to have focal segmental glomerulosclerosis and associated hypoparathyroidism and sensorineural deafness. The child progressed to end stage renal failure and was successfully managed by dialysis and cadaveric renal transplantation. He later developed progressive neurological deterioration and mitochondrial myopathy and neuropathy was diagnosed.
Sustained complete remission of steroid- and cyclophosphamide-resistant minimal-change disease with a single course of rituximab therapy
AbstractWe report a case of steroid- and cyclophosphamide-resistant nephrotic syndrome secondary to minimal-change disease occurring in an otherwise healthy 19-year-old female, responding rapidly to two doses of rituximab therapy. Complete disease remission has been sustained up to last follow-up (32 months) despite CD19 recovery. Literature review suggests emerging evidence that rituximab may have a role to play in recurrent and/or refractory minimal-change disease.
Paediatric Nephrology Journal of Bangladesh · 2023 · 1 citations · open access
Familial nephrotic syndrome: Does it matter?
AbstractAbstract Steroid sensitive nephrotic syndrome (SSNS) is the most common form of nephrotic syndrome in childhood. Familial SSNS seems to be clinically homogeneous but reports on genetically informative SSNS families are lacking. Familial SSNS was found to be genetically distinct from familial steroid resistant nephrotic syndrome (SRNS). Several genes have been identified for SRNS. In general, genetic forms of nephrotic syndrome are resistant to common therapeutic approaches. But different cohort of steroid sensitive familial nephrotic syndrome were published. So precise clinical and genetic information on familial nephrotic syndrome are still lacking. Whether family history of nephrotic syndrome influences outcome is still in dilemma.
Proceedings for Annual Meeting of The Japanese Pharmacological Society · 2018 · 0 citations · open access
Mild electrical stimulation and heat shock suppress renal pathology in adriamycin-induced nephrotic syndrome model
AbstractNephrotic syndrome (NS) is characterized by large amounts of proteinuria, hypoalbuminemia and edema. In clinics, steroids are selected as first-choice drug for therapy of NS. However, some NS patients exhibit steroid-resistant NS. Because there is no cure for these patients, development of novel therapy is urgently needed. Previously, our laboratory has shown that MES+HS ameliorates the pathologies of hereditary kidney disease, Alport syndrome. Here, we investigated the effects of MES+HS on the pathologies of NS in an attempt to establish a novel, steroid-independent NS therapy.
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.
DeCure is a research and publication project, not medical advice and not a treatment. "DeCure for X" describes a research goal, not a claim that a cure exists. Backing a cure is a contribution to fund the research — it is not an investment, and confers no yield, royalty, equity or IP ownership. Papers are published open-access by the DeCure.ai DAO.
