DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for primary hyperoxaluria — screening already-approved drugs against its 7-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 maps to a 7-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 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
hydroxyacid oxidase 1 (HAO1) — HAO1 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 fmndrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 2NZL · 1.35 Å · ligand FLAVIN MONONUCLEOTIDE (FMN). Experimental structure, not a prediction.
What the evidence adds up to
Primary hyperoxaluria is a group of very rare autosomal recessive disorders caused by impaired glyoxylate metabolism in the liver, leading to overproduction and accumulation of oxalate. The kidney is the main target organ because oxalate cannot be metabolised and is excreted in the urine, causing nephrocalcinosis, recurrent urolithiasis, and eventual renal impairment. Type 1, the most common form, results from mutations in the AGXT gene and typically presents with recurrent stones and nephrocalcinosis from childhood to early adulthood, progressing to chronic and end-stage kidney disease at any age.
The only specific therapy available as of 1978 was pyridoxine, which lowers urinary oxalate in a proportion of cases but not all. One case report described a patient whose urinary oxalate fell and renal function improved on pyridoxine, which the authors believed was the first such improvement described. No controlled trial data are provided in these abstracts, and the proportion of patients who respond is not quantified.
For patients who progress to kidney failure, liver-kidney transplantation has been the only efficient therapy, particularly for those in countries that cannot afford newer RNA-interference drugs. A 2024 retrospective study of ten type 1 patients reported that five received simultaneous liver-kidney transplantation and five received sequential transplantation, with a median postponement of the kidney transplant of 8 months (range 4–20). Five patients were from medium-low income countries. At 6 and 12 months, biopsies showed calcium oxalate crystal precipitation in seven patients, indicating recurrence of deposition despite the delay between liver and kidney transplantation. No differences in kidney function or post-transplant oxalate precipitation were observed between patients who had bilateral nephrectomy and those who did not. As of most recent follow-up, none of the patients had lost their kidney graft. The study concludes that adapting the transplant strategy to individual cases can be successful, but it does not report graft survival rates or patient survival with confidence intervals.
What is still missing are large, prospective, controlled trials that can define which patients respond to pyridoxine and at what dose, and whether newer RNA-interference therapies can prevent or delay the need for transplantation. The transplant data come from a single-centre retrospective series of only ten patients, with no randomisation and no long-term follow-up beyond the observation period. Patient stratification by genotype, residual enzyme activity, and age at intervention remains unexplored in these abstracts.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
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.
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.
Simultaneous or sequential kidney-liver transplantation in primary hyperoxaluria
AbstractBACKGROUND: Primary hyperoxaluria type 1 is responsible for pediatric kidney failure in 1 to 2% of cases. Novel therapies based on RNA interference are changing the natural history of the disease. However, for those who do progress to kidney failure, and for patients living in countries that cannot afford these expensive therapies, liver-kidney transplantation may remain the only efficient therapy. METHODS: The aim of the study was to evaluate the outcome of patients with primary hyperoxaluria type 1 who received simultaneous or sequential liver-kidney transplantation. We retrospectively evaluated 10 patients, five of whom received a simultaneous transplantation, and five underwent sequential transplantation, with a median postponement of the kidney transplantation of 8 months (range 4-20). Among the patients, 5 were from medium-low income countries. RESULTS: (range 29.9-77.5) in those with sequential transplantation (p:NS). Biopsies performed at 6 and 12 months showed precipitation of calcium oxalate crystals in 7 patients, demonstrating the recurrence of deposition despite the delay between liver and kidney transplantation. No differences in kidney function or in post-transplant renal oxalate precipitation were observed between patients that underwent bilateral nephrectomy and those who did not. As of their most recent follow up, none of the patients has lost their kidney graft. CONCLUSIONS: Our study shows that by adapting the transplant strategy to individual cases, patients with primary hyperoxaluria type 1 can be successfully treated.
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.
