DeCure's autonomous Nephrology AI scientist is researching a drug-repurposing hypothesis for IGA glomerulonephritis — screening already-approved drugs against its 35-gene Open Targets disease module to publish open-access research. Research is fast; the path to publication is funded in milestone stages.
Disease moduleIGA glomerulonephritis maps to a 35-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
Structures already discussed alongside iga glomerulonephritis in the retrieved literature, rendered from public PubChem SMILES. Which drugs appear here reflects the evidence found, not a ranked prediction.
Molecular view
nuclear receptor subfamily 3 group C member 2 (NR3C2) — NR3C2 is one of the genes in this disease's Open Targets module — part of the target space DeCure's repurposing candidates point at. The protein backbone is drawn as a cartoon. The structure has 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1h-pyrazol-4-yl]-2h-1,4-benzoxazin-3(4h)-one bound in it, shown as sticks.
Loading structure…
helix sheet 2,2-difluoro-3-hydroxypropyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4PF3 · 1.1 Å · ligand 6-[1-(2,2-difluoro-3-hydroxypropyl)-5-(4-fluorophenyl)-3-methyl-1H-pyrazol-4-yl]-2H-1,4-benzoxazin-3(4H)-one (HFN). Experimental structure, not a prediction.
What the evidence adds up to
A single case report describes an 8-year-old boy with IgA nephropathy whose urinary protein-to-creatinine ratio fell from 520 mg/mmol to 69 mg/mmol and whose serum creatinine normalised to 69 μmol/L after six months of targeted-release budesonide (starting at 3 mg daily, increasing to 6 mg daily). The child had previously not responded to pulse methylprednisolone, oral prednisolone, enalapril, and irbesartan. No side effects were reported. The authors note that the NEFIGAN trial in adults showed dose-dependent results, with 8 mg/day producing stable proteinuria and 16 mg/day producing significant improvement, and they caution that trial data are needed to confirm the results can be generalised to children.
A multicentre study of 33 adult IgAN patients (median age 45, 25 men, 8 women) treated with 16 mg/day targeted-release budesonide for nine months with one month tapering found that proteinuria fell from 2.76 ± 1.7 g/24 hr at baseline to 1.67 ± 1.18 g/24 hr at 10 months (p = 0.004). eGFR remained stable (58.93 ± 24.83 ml/min/1.73 m2 at baseline vs 56.01 ± 26.04 at 10 months, p = 0.244). Only 10 of 33 patients achieved proteinuria below 1 g/24 hr. Those who did were more likely to have endocapillary hypercellularity (E1) and crescent formation (C1) on biopsy (p = 0.015 and p = 0.041 respectively), suggesting that active histological lesions predict a better response.
Sparsentan, a dual endothelin and angiotensin II receptor antagonist, was approved by the US FDA in January 2023 for IgA nephropathy. Reviews describe it as a once-daily add-on therapy that limits proteinuria and progression to end-stage kidney disease without weakening the immune system. The approval is based on multiple clinical trials including DUET, PROTECT, SPARTACUS, and SPARTAN. A phase 2 study (EPPIK) is examining sparsentan’s potential and safety in children with focal segmental glomerulosclerosis, IgA nephropathy, Alport syndrome, and other conditions.
What remains missing are randomised controlled trials confirming the efficacy of targeted-release budesonide in children, longer-term outcome data for both drugs beyond proteinuria reduction, and prospective studies that use histological stratification to guide treatment selection. The cost and infrastructure for large multicentre trials, as well as clear criteria for which patients benefit most from each agent, 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.
Journal of Paediatrics and Child Health · 2018 · 12 citations · open access
Childhood IgA Nephropathy Successfully Treated with Targeted‐Release Budesonide: A Case Report
AbstractIdiopathic immunoglobulin-A (IgA) nephropathy is a primary glomerulonephritis with varying clinical presentations. Treatment regimens are often poorly tolerated and yield variable results.1 The NEFIGAN Trial (targeted-release budesonide vs. placebo in patients with IgA nephropathy) demonstrated that targeted-release-formulation budesonide (TRF-budesonide), in conjunction with optimal renin-angiotensin system blockade, safely reduced proteinuria in adults with IgA nephropathy.2 The authors suggest that TRF-budesonide targets the high density of Payer's patches in the ileum, which suppresses the dysfunctional mucosal immune system. To our knowledge, this report details the first successful trial of this therapy in a paediatric patient. An 8-year-old boy was diagnosed with IgA nephropathy following an episode of haematuria. At presentation, his serum creatinine was 79 μmol/L, and his urinary protein-to-creatinine ratio (uPCR) was >800 mg/mmol. A kidney biopsy demonstrated features of IgA mesangioproliferative glomerulonephritis with focal segmental sclerosis (55%) and crescents (25%) (M1, E1, S1, T0). He received 25 mg/kg of pulse methylprednisolone daily for 3 days, followed by a tapering course of prednisolone over 6 months. He continued to have synpharyngitic, macroscopic haematuria and exacerbations of nephrotic-range proteinuria despite adding 15 mg of enalapril daily. At 3.5 years post-diagnosis, he underwent repeat kidney biopsy, which showed active mesangioproliferative IgA nephropathy, worsening sclerosis (61%), new tubular atrophy (30%) and crescents (25%) (M1, E1, S1, T1). Despite further courses of oral prednisolone (1 mg/kg/day with slow tapering regimes) and the addition of 75 mg of irbesartan daily, his creatinine increased to 90 μmol/L and uPCR to 520 mg/mmol. Now 12 years old and demonstrating persistent nephrotic-range proteinuria, he was commenced on a trial of 3 mg of TRF-budesonide daily, which increased to 6 mg daily after 4 weeks. He remained on enalapril and irbesartan during this 6-month trial. He had a positive response, with his uPCR falling from 520 mg/mmol to 69 mg/mmol and serum creatinine normalising to 69 μmol/L. The dose of TRF-budesonide was well tolerated, and no side effects were reported. Following this successful trial, we have commenced a weaning regime of 3 mg daily for 6 months, with second-daily dosing planned thereafter. The NEFIGAN trial demonstrated dose-dependent results; adults treated with 8 mg/day had stable uPCR, yet the 16 mg/day group showed significant improvement.2 In our paediatric patient, a targeted treatment dose of 6 mg daily was used, with a formulation approved by our centre's Drug and Therapeutics Committee for the treatment of inflammatory bowel disease. It is possible that higher dosing may have resulted in more rapid improvement or conversely impeded treatment due to side effects. This case suggests that localised steroid formulations may have a role in treating IgA nephropathy in children. Ultimately, trial data is required to confirm that the NEFIGAN results can be safely generalised to children.
Expert Review of Clinical Pharmacology · 2025 · 3 citations
Sparsentan: a dual endothelin and angiotensin II receptor antagonist approved for IgA nephropathy
AbstractINTRODUCTION: IgA nephropathy (IgAN) is the most common primary glomerulonephritis. For decades, the only medication treatments that were widely accepted were the use of renin-angiotensin aldosterone inhibitors and corticosteroids. The early 2020s have brought a flurry of new treatments to the once dark IgA treatment landscape. Sparsentan is a novel dual-endothelin angiotensin receptor antagonist that has been approved as an add-on therapy for the treatment of IgAN. AREAS COVERED: We discuss the treatment landscape and the unmet needs for treating IgA nephropathy. Multiple clinical trials showing the efficacy of sparsentan including DUET, PROTECT, SPARTACUS, and SPARTAN will be described. Additionally, we will preview the future options for IgA patients. EXPERT OPINION: Sparsentan is a major step forward in improving outcomes for patients with IgAN. This once-a-day agent, in addition to other standards of care, limits proteinuria and progression to ESKD and kidney transplantation. The ability to lower proteinuria without weakening the immune system is a substantial gain for patients. As an agent that impacts the glomeruli directly, sparsentan is able to limit damage in mechanisms that previous RASi and steroids have not. Including sparsentan in the combination treatment for IgAN must be considered for adequate kidney protection.
Journal of Nephropharmacology · 2023 · 0 citations · open access
Targeted-release budesonide in immunoglobulin A nephropathy; a mini-review
AbstractImmunoglobulin A nephropathy is the most common kind of primary glomerulonephritis worldwide and one of the main causes of renal failure. Systemic corticosteroid therapy may protect against renal deterioration in IgA nephropathy; however, it is not often advised for long-term treatment due to possible side effects. Recent studies present promising results of the new targeted-release formulation of budesonide that delivers the drug to the distal ileum to reduce side effects for patients with IgA nephropathy. In this paper, we highlighted the potential benefits of budesonide as a treatment option for IgA nephropathy and the need for additional studies to confirm its effectiveness. The lack of alternative treatments to prevent renal deterioration without other systemic side effects motivated us to gather relevant information to fill this gap. In this brief overview, we have reviewed some of the most recently published studies regarding how budesonide protects against IgA nephropathy. Studies reveal that budesonide might significantly decrease proteinuria, hematuria, and creatinine level while maintaining normal renal function. Though, a limited number of trials have been established to date, and further investigations are needed to confirm the benefit of the new targeted-release budesonide in treating IgA nephropathy.
#808 Targeted release budesonide (TRB) can effectively reduce proteinuria when active lesions are present in IgA Nephropathy (IgAN) patients: A multicenter study
AbstractAbstract Background and Aims IgA Nephropathy (IgAN), the most dominant primary glomerulonephritis worldwide, is associated with a variety of histological lesions, which are classified and graded according to the MEST-C classification system. This classification tool can provide information regarding to prognosis, but it cannot guide treatment strategies. The recurrent nature of the disease often leads to frequent relapses, which require multiple rounds of corticosteroid therapy, posing challenges for long-term management. Recent evidence shows that targeted release budesonide (TRB) can effectively inhibit the first immunological steps taking place in Peyer patches in distal ileum, but also healing glomerular damage due to the minor absorption in systematic circulation causing no life-threatening side-effects. Method Adult IgAN patients, diagnosed the last 10 years, maintaining eGFR >30 ml/min/1.73 m2 and Uprotein >750 mg/24 hr, despite standard supportive treatment for at least 6 months, commenced on a 9-month TRB treatment, 16 mg/d with 1 month tapering, and followed regularly in the outpatient clinic. Renal biopsies were re-evaluated and scored according to Oxford classification. Parameters of renal function were monitored during TRB administration in a 3 month basis, at 0, 3, 6, 10 months, T0, T3, T6, 10, respectively. Results Thirty-three IgAN patients, M/F:25/8, Median age: 45 (38.5–65) years, from four different departments, included in the study. During the period between diagnosis and the initiation of treatment, [37 (22–87) months] eGFR declined from 64.99 ± 24.95 ml/min/1.73 m2 to T0, 58.93 ± 24.83 ml/min/1.73 m2, P = 0.063, and Uprot (2.87 ± 1.96 gr/24 hr) presented a minor decline to Uprot = 2.76 ± 1.7 gr/24 hr, P = 0.309 (T0). After commencing on TRB, T0–T3: 2.76 ± 1.7 − 2.31 ± 1.82 gr/24 hr, P = 0.225, T3-T6 2.31 ± 1.82 − 1.85 ± 1.69 gr/24 hr, P = 0.048, T6-T10 1.85 ± 1.69 − 1.67 ± 1.18 gr/24 hr, P = 0.052 and from T0 to T10: 2.76 ± 1.7 − 1.67 ± 1.18 gr/24 hr, P = 0.004. (Fig. 1) Simultaneously, eGFR remained stable during follow up. (56.01 ± 26.04 ml/min/1.73 m2) has been decreased since treatment initiation (eGFR -T0 = 58.93 ± 24.83 ml/min/1.73 m2), P = 0.244. Despite significant improvement in the severity of proteinuria, only 10/33 patients managed to reduce Uprot <1 gr/24 hr at the end of the study. This group of patients were characterized by the presence of endocapillary hypercellularity (E1) and crescent formation (C1), P = 0.015 and P = 0.041, with Phi's value of 0.438 and 0.367, respectively, indicating that IgAN patients presenting these lesions are more likely to respond to treatment. Conclusion A 10-month TRB administration can effectively reduce proteinuria in IgAN patients. The presence of E1 and/or C1 in kidney biopsy can be considered favorable prognostic indicators when TRB is administered. Both of these lesions are indicative of ongoing immunological activity and TRB can effectively reduce proteinuria.
Journal of Nephropathology · 2023 · 0 citations · open access
Advances in IgA nephropathy management, from pathological insights to personalized treatment
AbstractIgA nephropathy is a common glomerulonephritis with variable clinical outcomes. The optimal treatment for this condition remains uncertain, and corticosteroid therapy is reserved for patients unresponsive to supportive treatment. The histopathologic examination has a significant role in the diagnosis and prognosis of IgA nephropathy, but its role in the initiation of corticosteroid therapy is still under debate. Recently, targeted release formulation (TRF)-budesonide has emerged as a promising treatment due to its localized delivery to the gut and low systemic adverse effects. This brief review aims to assess recent advancements in IgA nephropathy management, focusing on applying Oxford classification in guiding corticosteroid therapy.
Clinical Case Reports and Studies · 2023 · 0 citations · open access
Sparsentan a New Dual Endothelin Angiotensin Receptor Antagonist: Synpharyngitic Glomerulonephritis
AbstractSparsentan a newly approved Dual Endothelin Angiotensin Receptor Antagonist for IgA nephropathy and glomerulosclerosis. Sparsentan drug known for its dual-action and high selectivity as it has the ability to target both Endothelin A receptor (ETAR) as well as Angiotensin II subtype 1 receptor (AT1R). According to EPPIK study (Phase-II), sparsentan's potential and safety for long-term Nephroprotection and Antiproteinuria in children with focal segmental glomerulosclerosis, IgA nephropathy, Alport syndrome will examined. IgA nephropathy, also known as synpharyngitic glomerulonephritis and Berger’s Disease (variations) is an immune system and kidney disease which is associated with inflammation of the glomeruli in the kidney. Sparsentan is certified by the US FDA In Jan 2023. In this review, the major events which resulted in initial approval of saparsentan for the treatment of patients with primary immunoglobulin A nephropathy are discussed.
Zenodo (CERN European Organization for Nuclear Research) · 2024 · 0 citations · open access
Sparsentan: A New Dual Endothelin Angiotensin Receptor Antagonist-Synpharyngitic Glomerulonephrities
AbstractSparsentan is a newly approved Dual Endothelin Angiotensin Receptor Antagonist for glomerulosclerosis and IgA nephropathy. Sparsentan is dual-acting, highly selective antagonist has as its targets both the Endothelin A Receptor (ETAR) and the Angiotensin II Subtype 1 Receptor (AT1R). In the Phase 2 EPPIK study, sparsentan's potential and safety for long-term Nephroprotection and Antiproteinuria in children with focal segmental glomerulosclerosis, Minimal Change Disease (MCD), IgA nephropathy, IgAV, and Alport Syndrome (AS) will be examined. IgA nephropathy, also known as Berger's disease (variations) and synpharyngitic glomerulonephritis, is an immune system and kidney disease. It is a particular kind of glomerulonephritis, which is an inflammation of the glomeruli in the kidney. Sparsentan is certified by the US FDA In January 2023. In this article, the major events that resulted in saparsentan initial approval for the treatment of people with primary immunoglobulin A nephropathy, proteinuria is present are discussed.
AbstractIgA nephropathy is the most common primary glomerulonephritis worldwide. The clinical spectrum covers a wide range of features from minor urinary abnormalities (asymptomatic hematuria and mild proteinuria with normal renal function) to acute and chronic renal insufficiency. Ideally, the goal of treatment would be to correct any defects in IgA1 glycosylation and to modify mesangial deposition or removal of IgA1 deposits. There are only a few randomized controlled trials in IgA nephropathy; for this reason most treatment options are largely based on expert opinion. Authors discuss therapeutic options of different clinical pictures and the optimized renoprotective treatment of all IgA nephropathy patients.
Disease module: DeepOracle (Open Targets). Approved indication: ChEMBL drug_indication (max_phase=4). Structures: RDKit from PubChem SMILES. Literature: retrieved by DeepSearch across 234,678,978 indexed works, 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.
