DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for primary hyperoxaluria type 2 — 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 modulePrimary hyperoxaluria type 2 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 primary hyperoxaluria type 2 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
glyoxylate and hydroxypyruvate reductase (GRHPR) — GRHPR 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 ndpdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2GCG · 2.2 Å · ligand NADPH DIHYDRO-NICOTINAMIDE-ADENINE-DINUCLEOTIDE PHOSPHATE (NDP). Experimental structure, not a prediction.
What the evidence adds up to
Primary hyperoxaluria type 2 is not the subject of any of the provided abstracts. The abstracts discuss primary hyperoxaluria type 1, the more common form caused by AGXT gene mutations, and general management of primary hyperoxalurias. No data on type 2 prevalence, genetics, or specific outcomes are given.
For type 1, the only specific drug therapy mentioned is pyridoxine (vitamin B6). A 1978 case report describes one patient in whom pyridoxine lowered urinary oxalate and improved renal function, but the authors note that pyridoxine works in only a proportion of cases. No response rates or sample sizes beyond that single case are provided. The 2000 review states that major advances have occurred but that specific questions remain unanswered.
Definitive treatment for type 1 is surgical: combined or sequential liver-kidney transplantation, or isolated liver or kidney transplantation, as described in a 2020 single-centre experience from South India. No survival or graft outcomes from that centre are reported in the abstract. A 2020 commentary on clinical trial endpoints for primary hyperoxaluria identifies kidney stone burden, estimated glomerular filtration rate, plasma oxalate, and urinary oxalate as important measures, but notes that stone burden is difficult to quantify and that data gaps remain.
What is still missing: no randomised controlled trials of any drug for primary hyperoxaluria type 2 are described; no validated surrogate endpoints for type 2 specifically are established; patient stratification by genotype or disease severity is not addressed in these abstracts; and funding for trials in such a rare disease is not discussed.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Drugs · 2022 · 44 citations · open access
Improving Treatment Options for Primary Hyperoxaluria
AbstractThe primary hyperoxalurias are three rare inborn errors of the glyoxylate metabolism in the liver, which lead to massively increased endogenous oxalate production, thus elevating urinary oxalate excretion and, based on that, recurrent urolithiasis and/or progressive nephrocalcinosis. Frequently, especially in type 1 primary hyperoxaluria, early end-stage renal failure occurs. Treatment possibilities are scare, namely, hyperhydration and alkaline citrate medication. In type 1 primary hyperoxaluria, vitamin B 6 , though, is helpful in patients with specific missense or mistargeting mutations. In those vitamin B 6 responsive, urinary oxalate excretion and concomitantly urinary glycolate is significantly decreased, or even normalized. In patients non-responsive to vitamin B 6 , RNA interference medication is now available. Lumasiran ® is already available on prescription and targets the messenger RNA of glycolate oxidase, thus blocking the conversion of glycolate into glyoxylate, hence decreasing oxalate, but increasing glycolate production. Nedosiran blocks liver-specific lactate dehydrogenase A and thus the final step of oxalate production. Similar to vitamin B 6 treatment, where both RNA interference urinary oxalate excretion can be (near) normalized and plasma oxalate decreases, however, urinary and plasma glycolate increases with lumasiran treatment. Future treatment possibilities are on the horizon, for example, substrate reduction therapy with small molecules or gene editing, induced pluripotent stem cell-derived autologous hepatocyte-like cell transplantation, or gene therapy with newly developed vector technologies. This review provides an overview of current and especially new and future treatment options.
Archives of Disease in Childhood · 2000 · 35 citations · open access
Current topic: Current approaches to the management of primary hyperoxaluria
AbstractPrimary hyperoxalurias (PH) are very rare diseases characterised by overproduction and accumulation of oxalate in the body. The main target organ is the kidney, as oxalate cannot be metabolised and is excreted in the urine, leading to nephrocalcinosis, recurrent urolithiasis, and subsequent renal impairment. During the last decade, major advances in enzymology, molecular genetics, and cell biology have generated excellent reviews on both pathophysiology and management 1 2 ; however, specific questions remain unanswered.
AbstractJournal Article Primary hyperoxaluria type I Get access R.W.E. WATTS R.W.E. WATTS From the Department of Medicine, Hammersmith HospitalLondon, UK Address correspondence to Dr R.W.E. Watts, The Consulting Rooms, Wellington Hospital, Wellington Place, London NW89LR Search for other works by this author on: Oxford Academic PubMed Google Scholar QJM: An International Journal of Medicine, Volume 87, Issue 10, October 1994, Pages 593–600, https://doi.org/10.1093/oxfordjournals.qjmed.a068871 Published: 01 October 1994
Fortschritte der Urologie und Nephrologie · 1978 · 2 citations
Reversal of chronic renal failure from primary hyperoxaluria on treatment with pyridoxine
AbstractThe only specific therapy available for treatment of primary hyperoxaluria is pyridoxine which will lower urinary oxalate in a proportion of cases but not all (1). We describe here a case in which treatment with Pyridoxine resulted in a lowering of urinary oxalate and subsequent improvement in renal function. It is believed that this is the first time that such improvement in renal function has been described.
Kidney International Reports · 2024 · 1 citations · open access
Bone Marrow Oxalosis
AbstractPrimary hyperoxaluria is a rare autosomal recessive genetic disorder due to impaired glyoxylate liver metabolism resulting in the accumulation of oxalate. Three types are described with a wide range of severity. Type 1 primary hyperoxaluria is the most common, caused by mutations in the alanine-glyoxylate aminotransferase (AGXT) gene. This results in recurrent nephrolithiasis and nephrocalcinosis from childhood to early adulthood, with the development of chronic and end-stage kidney disease at any age 1.
Kidney International Reports · 2020 · 0 citations · open access
SUN-331 COMBINED LIVER KIDNEY TRANSPLANTATION FOR PRIMARY HYPEROXALURIA: SINGLE CENTRE EXPERIENCE IN SOUTH INDIA
AbstractType 1 primary hyperoxaluria is a rare inherited autosomal recessive disorder, characterized by deficiency of the hepatic enzyme alanine glyoxylate aminotransferase, leading to increased oxalate production, nephrocalcinosis, urolithiasis, and systemic oxalosis. Early diagnosis and management is pivotal as medical management and definitive treatment in the form of combined or sequential liver-kidney transplantation, isolated liver or kidney transplantation have been studied to transform disease outcomes.
The Journal of Urology · 2020 · 0 citations · open access
Re: Endpoints for Clinical Trials in Primary Hyperoxaluria
AbstractPatients afflicted with primary hyperoxaluria (PH), especially type 1, are at risk for chronic kidney disease, with many progressing to end stage renal disease.Novel treatments have been developed to reduce endogenous oxalate production in those with type 1 PH, which may significantly benefit this cohort.Regulating bodies such as the U.S. Food and Drug Administration use clinical end points to assess the effectiveness of a treatment before approval.This esteemed group of PH investigators identified kidney stone burden, estimated glomerular filtration rate, plasma oxalate and urinary oxalate excretion as important outcomes/end points for assessment.Stone burden is the most difficult end point to quantify.Plain imaging might not capture true burden since it is only a 2-dimensional assessment.Ultrasonography is frequently inconsistent and does not permit an accurate volume measurement.While stone volume can be captured with computerized tomography, there are concerns regarding radiation exposure, which can be limited by use of targeted low dose imaging.Renal function may help direct how to determine the usefulness of the end point.The authors point out gaps in the data that need to be filled.
Nephrology and Dialysis · 2025 · 0 citations · open access
Clinical characteristics of Russian children with primary hyperoxaluria. Results of a pilot study of lumasiran therapy of primary hyperoxaluria type 1
AbstractPrimary hyperoxaluria is a severe autosomal recessive disorder that leads to chronic kidney disease and often necessitates renal replacement therapy in childhood. Some patients with primary hyperoxaluria type 1 respond to pyridoxine therapy, whereas patients with types 2 and 3 receive only citrate therapy. In recent years, a targeted drug – lumasiran – has become available for treating 1 type primary hyperoxaluria. Its mechanism is based on reducing glioxylate production and, consequently, oxalate formation. To date, no published data exist on the efficacy of lumasiran in Russian patients. Materials : Since 2014, 14 children with primary hyperoxaluria have been followed in the Nephrology Department of the National Research Center for Children’s Health: 12 with 1 type and 2 with type 3. Among the 12 children type 1 patients, 5 received pathogenetic therapy with lumasiran. The duration of treatment ranged from 9 months to 3 years, with a mean 26 months (SD 13 months). Results : After 12 months of therapy, no patients showed worsening of nephrocalcinosis or decline in kidney function. Four patients achieved marked reduction in urinary oxalate excretion (90%, 88%, 89% and 74%). One child had been on treatment for less than one year. Conclusions : Early treatment initiation of treatment for primary hyperoxaluria – particularly type 1 – significantly improve not only renal but also overall survival.
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.
