DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for familial nephrotic syndrome — screening already-approved drugs against its 3-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleFamilial nephrotic syndrome maps to a 3-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 nephrotic syndrome 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
Two young adults with nephrotic syndrome developed pulmonary embolism, one fatally. The first patient, who had been diagnosed with nephrotic syndrome more than ten years earlier, presented with gradually worsening dyspnoea that was initially misdiagnosed as myocarditis and died. The second patient presented with sudden shortness of breath after treatment for nephrotic syndrome; his pulmonary embolism was diagnosed quickly, anticoagulant therapy was started promptly, and at 30-day follow-up his symptoms had disappeared and his abnormal laboratory results had returned to almost normal. The authors conclude that the possible occurrence of pulmonary embolism in a young person with nephrotic syndrome should not be ignored, and that early versus delayed diagnosis leads to different clinical outcomes.
A 2019 press release from Kidney Research UK describes research into why a faulty gene involved in nephrotic syndrome leads to disease in some patients. The release states the findings could pave the way for new ways to prevent or treat the condition by revealing new targets to intervene, but provides no specific data, no drug tested, and no patient outcomes. It notes that around 1 in 50,000 children are diagnosed with nephrotic syndrome each year.
A 1981 commentary questions a controlled study by Vance et al on the effects of nephrotic syndrome on the family. The commentary argues that the study’s conclusion — that the frequency of serious problems experienced by parents and siblings of children with nephrotic syndrome may not be as great as once assumed — is inadequately supported by data consisting mainly of self-assessments. The commentary notes that an individual’s assessment of their own problems usually differs considerably from an interviewer’s more objective judgment and from scores on a standardised test.
No drug is tested or recommended in any of these abstracts. No survival rates, response rates, or sample sizes beyond the two case reports are given. What is still missing is any controlled trial data, any drug intervention tested in patients, any genetic stratification linking the faulty gene to a specific treatment, and any funding for a prospective study of pulmonary embolism prophylaxis in young adults with nephrotic syndrome.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Medicine · 2018 · 13 citations · open access
Nephrotic syndrome with acute pulmonary embolism in young adults
AbstractINTRODUCTION: Pulmonary embolism (PE) is often misdiagnosed, or the diagnosis is delayed because of its diverse clinical manifestations, it may even remain asymptomatic until sudden death. Most risk factors are not associated with young people, and there is a paucity of literature regarding PE in children and young adults. CASE PRESENTATION: Patient 1 who died was diagnosed with nephrotic syndrome more than 10 years before. He presented to a clinic with gradually worsening dyspnea, which was initially misdiagnosed as myocarditis. Patient 2 presented with sudden shortness of breath after treatment for nephrotic syndrome. His PE was quickly diagnosed, allowing prompt initiation of anticoagulant therapy. At follow-up 30 days after hospital discharge, his symptoms had disappeared, and his abnormal laboratory results had returned to almost normal. CONCLUSION: The diagnosis and treatment of the above 2 patients suggest that the possible occurrence of PE in a young person with nephrotic syndrome should not be ignored. The early diagnosis and delayed diagnosis will have different clinical outcomes.
Dasatinib Induced Reversible Nephrotic Range Proteinuria Occurs More Frequently Compared to Other Tyrosine Kinase Inhibitors in the Treatment of Chronic Myeloid Leukemia
AbstractAbstract Introduction: Dasatinib is an oral inhibitor of Abl and Src family of kinases. Dasatinib can cause a pleural effusion in 14% to 30% of patients as well as pulmonary arterial hypertension. Its mechanism is not fully elucidated although vascular endothelial growth factor (VEGF)-mediated mechanism has been proposed. In the literature, there are sporadic case reports of dasatinib-induced proteinuria/nephrotic syndrome. It is also suggested that dasatinib-induced kidney injury involves the interruption of VEGF signaling pathway. In the present study, we present a series of 6 patients, who developed nephrotic-range proteinuria while on dasatinib therapy that resolved after switch to other TKIs or discontinuation. Also, we have analyzed the risk of TKI-associated proteinuria according to the TKI subtype in 256 CML patients having available results of urine protein level. Patients and Methods: A total of 256 patients with CML on TKIs, with available urine testing were reviewed. TKI therapy was as follows: Imatinib (n=147), dasatinib (n=67), nilotinib (n=13), ponatinib (n=13) and bosutinib (n=16). First, we have reviwed spot urinalysis result for proteinuria screening, and further reviewed in detail the result of 24-hour urine protein measurement. If proteinuria is detected, we had in-depth chart review on the case to exclude other causes of proteinuria such as diabetes, renal failure, urinary tract infecion or urinary tract malignancies, etc. After excluding other causes of proteinuria, we have calculated the incidence rate of proteinuria using 1,000 person-year considering duration of exposure to TKI therapy. Results: With median duration of 35 months of dasatinib therapy, 6 patients (8.9%) developed nephrotic range proteinuria, after excluding other secondary causes of proteinuria. All received dasatinib as 2nd line following Imatinib front line therapy. Out of 6 patients with proteinuria, 4 patients developed pleural effusion prior to the development of proteinuria. All of them showed optimal molecular response to dasatinib therapy at the time of proteinuria development including MR4.5 (n=4), MR4.0 (n=1) or MMR (n=1). One patient underwent renal biopsy which showed chronic glomerular endothelial cell injury and thin basement membrane nephropathy, consistent with finding of minimal change disease. All 6 cases had discontinued (n=3) or switched to other TKI therapy (imatinib n=1; botutinib n=1; nilotinib n=1) with complete resolution of proteinuria. In the 3 patients who had MR4.5 or deeper response when dasatinib was discontinued due to proteinuria, one lost MMR after 3 months, one maintained MMR (+13 months), and another without losing undetectable transcript level (+21 months). The incidence rate of TKI-associated proteinuria was analyzed according to the TKI subtype in 256 CML patients. Median follow-up duration was 31 months for 35 months for dasatinib (1-105 months), imatinib (1-172 months), 27 months for nilotinib (1-63 months), 5 months for bosutinib (1-22 months), and 1 month for ponatinib (1-14 months), respectively. The exposure year was 201.8 years in dasatinib (n=67), 523.2 years in imatinib (n=147), 31.4 years in nilotinib (n=13), 6.1 years in bosutinib (n=16) and 1.4 years in ponatinib (n=13). The incidence rate of proteinuria in dasatinib treated group was calculated as 29/1,000 person-year, while it was 0 in imatinib, nilotinib, bosutinib, ponatinib-treated group, respectively due to no case confirmed to have proteinuria after excluding secondary causes of proteinuria (Fisher's exact test p Conclusion: Development of nephrotic range proteinuria can be a toxicity from dasatinib therapy in CML treatment. Incidence rate is unexpectedly high at 29/1,000 person-year while there are no cases of nephrotic range proteinuria with exposure to other TKIs. All the proteinuria events were reversed completely after discontinuation/switch of dasatinib. Medical attention is to be paid for this unusual toxicity related to dasatinib therapy. Further study is strongly warranted to reach a clear conclusion for the incidence of this toxicity in a larger cohort. Disclosures Kim: BMS: Consultancy, Honoraria, Research Funding; Novartis: Consultancy, Honoraria, Research Funding; Paladin: Consultancy; Pfizer: Consultancy.
Scientists reveal how a faulty gene leads to kidney disease
AbstractResearch funded by Kidney Research UK has provided new insights into why a faulty gene involved in nephrotic syndrome leads to disease in some patients. The findings could pave the way for new ways to prevent or treat the condition, by revealing new targets to intervene in the process. Around 1 in 50,000 children are diagnosed with nephrotic syndrome each year.
Nephrotic Syndrome Family Self-Assessments Questioned
AbstractThe report by Vance et al "Effects of Nephrotic Syndrome on the Family: A Controlled Study"1 warrants further comment. The authors conclude that in general the frequency of serious problems experienced by parents and siblings of children with nephrotic syndrome may not be as great as was once assumed. Their conclusion is inadequately supported by data which consist mainly of self-assessments. Usually an individual's assessment of his/her problems differs considerably from an interviewer's more objective judgment and from scores on a standardized test.
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.
