DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for nephronophthisis — screening already-approved drugs against its 26-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleNephronophthisis maps to a 26-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 nephronophthisis 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
X-prolyl aminopeptidase 3 (XPNPEP3) — XPNPEP3 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 12pdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5X49 · 1.65 Å · ligand DODECAETHYLENE GLYCOL (12P). Experimental structure, not a prediction.
What the evidence adds up to
Familial juvenile nephronophthisis typically presents after 6 years of age through adolescence, with insidious early symptoms of polyuria and polydipsia that are often overlooked because urinalysis remains relatively normal and there is no proteinuria, azotemia, or hypertension. Most patients are not diagnosed until after the onset of renal failure. In a retrospective study of 180 kidney transplant recipients, 17 patients (9.4%) with juvenile nephronophthisis had a mean age of 12.6 ± 4.3 years and a mean follow-up of 79.5 ± 41.9 months post-transplant. Among these 17 patients, 70.6% received living related donor transplants and 23.5% had preemptive transplants. The acute rejection rate was significantly lower in the nephronophthisis group (17.6%) compared to patients with other primary diagnoses (34%), but 1-year and 5-year glomerular filtration rates were similar between groups (96.7 ± 23.2 vs 97.6 ± 28.4 mL/min/1.73 m2 at 1 year; 84.7 ± 31.1 vs 86.7 ± 21.7 at 5 years). The authors concluded that post-transplant prognosis was good.
No treatment exists beyond supportive care and kidney transplant. In cultured kidney tubular cells from NPHP1 patients, prostaglandin analogues were previously identified as candidate molecules that rescue ciliogenesis defects. A 2025 study tested a ROCK inhibitor and Eupatilin, identified by other groups, in kidney cells from NPHP1 and IQCB1/NPHP5 patients and in a zebrafish nphp mutant line. Eupatilin partially rescued NPHP1-associated ciliogenesis defects, and transcriptomic analysis suggested it inhibited cell cycle progression. Ciliary defects in NPHP5 patient cells were rescued by both prostaglandins and Eupatilin, but only prostaglandin analogues reduced pronephric cyst size in the zebrafish model. The study indicates these molecules can show beneficial effects across genetic contexts.
Nephronophthisis is an autosomal recessive cystic kidney disease caused by mutations in more than 25 genes (NPHP1-20, NPHPL1, NPHPL2), with all gene products localising to the primary cilium. The abnormal structure or function of primary cilia involves Hh, Wnt, Hippo, and DDR signalling pathways. Up to 2018, mutations in 18 different genes had been described.
What is still missing: no clinical trial has tested any of these candidate molecules in patients; the cell and zebrafish data are preclinical and do not yet show whether any compound slows kidney function decline in humans; patient stratification by specific NPHP gene mutation may be required, but the registry and genetic data remain incomplete; funding for a clinical trial and a properly designed, stratified study with kidney function endpoints is 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.
Clinical Pediatrics · 1986 · 26 citations
Familial Juvenile Nephronophthisis
AbstractFamilial juvenile nephronophthisis (FJN) is a frequent cause of chronic renal failure in children and adolescents. Typically it presents after 6 years of age through adolescence, but may become apparent in early childhood. The clinical presentation is insidious, and the early symptoms of polyuria and polydipsia are often overlooked in the presence of a relatively normal urinalysis and in the absence of proteinuria, azotemia, and hypertension. Thus most patients are not diagnosed until after the onset of renal failure. These children are excellent candidates for properly selected transplantation.
Familial Juvenile Nephronophthisis—Report of Cases in Two Siblings—
AbstractTwo brothers who have shown symptoms and signs typical of the so-called ‘familial juvenile nephronophthisis’ since about seven years of age are presented. Both are still alive and in chronic renal failure. Renal biopsy performed in one case (H.K.) revealed the typical changes described in the literature. An electron microscopic study showed many electron dense bodies in the proximal tubular epithelium.
Experimental and Clinical Transplantation · 2022 · 2 citations
Long-Term Outcomes of Kidney Transplant Recipients With Juvenile Nephronophthisis
AbstractOBJECTIVES: Nephronophthisis is the most common genetic cause of kidney failure in childhood. Treatment for nephronophthisis is symptomatic, and kidney transplant is a good treatment option when kidney failure has developed. We reported the outcomes of kidney transplant recipients with primary diagnosis of juvenile nephronophthisis who were followed-up in our center. MATERIALS AND METHODS: We retrospectively examined medical records of 17 kidney transplant patients with a primary diagnosis of juvenile nephronophthisis. We compared this group of 17 patients with kidney transplant recipients who had other etiologies of kidney failure in terms of transplant age, donor type, immunosuppressive treatment, acute rejection, graft loss rates, and glomerular filtration rates at 1 and 5 years posttransplant (N = 180 total analyzed). RESULTS: Among 180 kidney transplant recipients, the 17 patients (9.4%) with nephronophthisis had a mean age of 12.6 ± 4.3 years and mean follow-up time posttransplant of 79.5 ± 41.9 months. Five of 17 patients received a kidney transplant from a deceased donor (29.4%), and the remaining 12 patients (70.6%) received transplants from living related donors. Preemptive kidney transplant was performed in 4 patients (23.5%). There was a statistically significant difference (P < .05) in terms of acute rejection between patients with nephronophthisis (17.6%) versus patients with other primary diagnoses (34%). However, the patients with nephronophthisis versus those with other primary diagnoses were similar (P > .05) in terms of transplant age (12.6 ± 4.3 vs 13.8 ± 6.7 years, respectively) and follow-up time (79.5 ± 41.9 vs 59.1 ± 38.8 months, respectively). Donor type, immunosuppressive treatment, and 1-year (96.7 ± 23.2 vs 97.6 ± 28.4 mL/min/1.73 m2) and 5-year (84.7 ± 31.1 vs 86.7 ± 21.7 mL/min/1.73 m2) glomerular filtration rates were also similar (P > .05) between groups. CONCLUSIONS: Posttransplant prognosis was good among kidney transplant recipients with juvenile nephronophthisis.
Kidney International Reports · 2025 · 2 citations · open access
Prostaglandin Analogs and Eupatilin as Treatments for Nephronophthisis
AbstractIntroduction Primary cilia are sensory antennas that are present on the majority of quiescent vertebrate cells where they mediate key signaling during development and in response to environmental stimuli. Defects in primary cilia result in a group of heterogeneous inherited disorders with overlapping phenotypes, called ciliopathies. Nephronophthisis is an autosomal recessive tubulo-interstitial kidney ciliopathy with more than 25 identified genes called NPHP . Presently, no treatment exists beyond supportive care and kidney transplant, underscoring the need for novel therapies. Methods Using a phenotypic screening approach in cultured cell lines, we previously identified prostaglandin analogues as candidate therapeutic molecules based on their ability to rescue ciliogenesis defects in kidney tubular cells from NPHP1 patients. Here, we have investigated the potential beneficial effects of ROCK inhibitor and Eupatilin, similarly identified by other groups in different NPHP contexts, in kidney cells from NPHP1 and IQCB1/NPHP5 patients as well as in a zebrafish nphp mutant line ( traf3ip1/ift54 ). Results Eupatilin partially rescued NPHP1 -associated ciliogenesis defects. Transcriptomic analyses pointed out that cell cycle progression was inhibited by Eupatilin, likely explaining its broad effects on cilia assembly. Interestingly, while ciliary defects also observed in NPHP5 patient cells were rescued by both prostaglandins and Eupatilin, only prostaglandin analogues were able to reduce pronephric cysts size in the used nphp zebrafish model. Conclusion Our study indicates that these molecules can show beneficial effects across genetic contexts and shed light on their potential as therapeutic interventions for nephronophthisis.
International journal of pediatrics · 2018 · 0 citations
Progress in genetics of NPHP related signaling pathway
AbstractNephronophthisis(NPHP), an autosomal recessive cystic kidney disease, is the most frequent genetic cause for end stage renal failure in the first thirty years of life.NPHP can be caused by Mutations in 22 genes(NPHP1-20, NPHPL1, NPHPL2), with abnormal structure or function of primary cilia, involved in Hh, Wnt, Hippo, DDR signaling pathways.Elucidating the pathogenic genes and possible pathogenesis would make a difference in prevention, diagnosis, treatment, prognosis, and genetic counseling of NPHP.This article reviews the pathogenic genetics and related signaling pathways.
Key words:
Nephronophthisis; Hh signal pathway; Wnt signal pathway; Hippo signal pathway; DDR signal pathway
AbstractAims: Nephronophthisis (NPH) is a major cause of end-stage renal failure in children. Up to date, mutations in 18 different genes (NPHP1–18) have been described of which the gene products all localize to the primary cilium. Mutations of these genes result in an impaired ciliary function, classifying NPH as one of the most common ciliopathies in childhood.
Features of diagnostics of fanconi’s nephronophthisis at the patient with the uremic syndrome which undergone related kidney transplantation
AbstractClinical observation of the child with Fanconi’s nephronophthisis, diagnosed at end-stage kidney disease is described. The late request for a medical care, and also a polymorphism of displays of terminal uremia considerably complicated and slowed down diagnostics of dysfunction of kidneys. Cooperation of nephrologists, geneticists, transplantologists gave the chance even at overdue diagnostics to provide an adequate medical care. Related kidney transplantation became a choice method in correction of an uremic syndrome and provided medico-social rehabilitation of the child with Fanconi’s nephronophthisis.
AbstractDr. Snivastava suggests the use of the term "nephronophthisis" for these conditions. Does this term mean anything to most people, and if it does, how is it appropriate here? Is Familial Uraemic Medullary Cystic disease really a wasting away of the nephron, i.e., the tubular apparatus from Bowman's capsule to the collecting ducts, as the name nephronophthisis suggests? Surely it is time we stopped using Greek terms which to most are meaningless and generally wrongly applied, as would seem to be the case here.
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.
