DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for primary hyperoxaluria type 1 — screening already-approved drugs against its 2-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 1 maps to a 2-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 1 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
In a cohort of 24 patients with primary hyperoxaluria type 1 in Iran, 13 received a sequential liver transplant, 8 a combined liver and kidney transplant, and 3 a preemptive liver transplant. All organs came from deceased donors. The study found no statistically significant difference in mortality, rejection, or need for haemodialysis after transplant between the sequential and combined groups. The authors concluded that liver transplant can be considered a treatment, and that combined or preemptive liver transplant could be proper options.
A single-centre experience in South India reported that combined liver-kidney transplantation, as well as sequential or isolated liver or kidney transplantation, have been studied to transform disease outcomes. No patient numbers or survival data were given in that report. Another case described an unusual presentation of primary hyperoxaluria type 1 as postpartum acute kidney injury, noting that the disease typically presents with recurrent nephrolithiasis in the second or third decade of life and progresses to end-stage renal disease.
The evidence for liver-based transplant strategies in primary hyperoxaluria type 1 comes from small, single-centre cohorts. No randomised trials exist. The Iranian study did not report long-term graft survival or systemic oxalosis outcomes, and the sample of 24 patients limits generalisability. What is missing is prospective, multi-centre data comparing transplant strategies head-to-head, standardised criteria for preemptive versus combined transplant, and any evidence for pharmacological therapies that might delay or avoid transplantation.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Experimental and Clinical Transplantation · 2019 · 16 citations
Liver Transplant for Primary Hyperoxaluria Type 1: Results of Sequential, Combined Liver and Kidney, and Preemptive Liver Transplant
AbstractOBJECTIVES: Primary hyperoxaluria type 1 is an autosomal recessive disorder that causes overproduction and urinary excretion of oxalate. Liver transplant has been suggested as a treatment for primary hyperoxaluria type 1 since the defective enzyme is expressed in the liver. This study aimed to investigate results of combined liver and kidney, sequential, and preemptive livertransplantin patients with primary hyperoxaluria type 1. MATERIALS AND METHODS: In this cohort study, we followed patients with primary hyperoxaluria type 1 who underwent liver transplant at our centerin Shiraz, Iran. Clinical and laboratory data of patients were gathered, and major outcomes, including renal failure after liver transplant, rejection, and mortality were recorded. Survival of patients was analyzed by the Kaplan-Meier method. RESULTS: Our study included 24 patients. There were 16 male (66.6%) and 8 female (33.33%) patients. Thirteen patients were in the pediatric age group (age < 18 y), and 11 patients were adults (age ≥ 18 y). Thirteen patients underwent sequential transplant, 8 patients underwent combined liver and kidney transplant, and 3 patients underwent preemptive transplant. All patients received organs from deceased donors. There were no statistically significant differences in mortality, rejection, and hemodialysis after transplant between those with sequential transplant and those with combined liver and kidney transplant (P > .05). CONCLUSIONS: Liver transplant can be considered a treatment for patients with primary hyperoxaluria type 1. Combined liver and kidney transplant and preemptive liver transplant could be proper options for these patients.
Scandinavian Journal of Urology and Nephrology · 1980 · 15 citations
Primary Hyperoxaluria
AbstractPrimary hyperoxaluria is a hereditary disease caused by an inborn error of glycine/glyoxalate metabolism. This study presents the results of a Scandinavian survey of patients with primary hyperoxaluria diagnosed and/or treated through the years 1967 to 1976. Altogether 17 patients, 13 males and four females, were reported. The age at onset of the disease varied between three months and 29 years and the age at diagnosis between eight months and 45 years. Ten of the patients were still alive at the end of 1976 at ages between 14 and 49 years. In diagnosing primary hyperoxaluria attention is paid to the simultaneous determinations of the urinary excretion of oxalic acid, glycolic acid and glyoxylic acid. None of the different therapeutic measures in primary hyperoxaluria have, so far, received extensive evaluation. At present, large doses of pyridoxine in combination with taurine seem worth further investigation with a larger number of patients.
Transplantation · 2021 · 10 citations · open access
Liver Transplantation in Primary Hyperoxaluria Type 1: We Have to Find an Alternative!
AbstractPrimary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by the functional defect of hepatic alanine-glyoxylate aminotransferase (AGT), resulting in the overproduction of oxalate (Figure 1). It leads to early end-stage renal disease (ESRD) in most patients.1 To date, the only way to cure PH1 patients with ESRD is dual liver-kidney transplantation.FIGURE 1.: Glyoxylate metabolism in the hepatocyte in primary hyperoxaluria type I. In the peroxisome of normal hepatocyte, GO catalyzes the conversion of glycolate to glyoxylate. Then AGT catalyzes the conversion of glyoxylate to glycine. In primary hyperoxaluria type 1, glyoxylate accumulates as a result of AGT deficiency and is converted to oxalate by hepatic LDH and GO and to glycolate by GRHPR. Oxalate and glycolate are finally eliminated from the body by the kidneys. AGT, alanine-glyoxylate aminotransferase; GO, glycolate oxidase; GRHPR, glyoxylate reductase-hydroxypyruvate reductase; LDH, lactate dehydrogenase.A 16-year-old anuric PH1 Algerian boy, on dialysis since 4 years, traveled to our center for sequential liver-kidney transplantation. Because of the presumed systemic oxalosis, the sequential approach was decided. He received an LT from his uncle in June 2020. The posttransplant course was complicated with infections, recurrent biliary strictures, encephalopathy, and persistent liver dysfunction. Two months of hospitalization in the intensive care unit led to severe malnutrition, sarcopenia, psychologic stress, and to unaffordable expenses for his parents. The patient is currently hemodialyzed in our center with a worrying medical condition. In addition to the organ access issue,2 LT is associated with nonnegligible morbidity and mortality. The European PH1 transplant registry experience reported 1-, 5-, and 10-year patient survival rates of 86%, 80%, and 69%, respectively.3 These results are not optimal. While LT was ethically justified until now—being the only way to cure the metabolic defect—it will no longer be the case in the near future. Indeed, innovative drugs are currently in the pipeline to treat hepatic metabolic defect. Preliminary results of Illuminate-A trial, a phase 3 trial that evaluates lumasiran (an RNA interference [RNAi] drug targeting glycolate oxidase; Figure 1) in PH1 patients with estimated glomerular filtration rate >30 mL/min, showed a dramatic decrease of urine oxalate levels at 6 months without important side effects.4 Currently, a phase 3 trial—Illuminate-C trial—is recruiting to evaluate the efficacy of lumasiran in PH1 patients with an estimated glomerular filtration rate of ≤45 mL/min, including chronic dialyzed patients (NCT04152200). If conclusive, it opens the possibility to consider treating PH1 patients with ESRD by combining this medication and kidney transplantation. Other drugs are currently tested in clinical trials, including oral administration of Oxabact (an anaerobic bacteria that uses oxalate as the sole source of energy), nedosiran (an RNAi drug targeting hepatic LDHA; NCT04042402; Figure 1), and stiripentol (an antiepileptic drug inhibiting LDH; NCT03819647; Figure 1).5 Allogenic hepatocyte transplantation has been unsuccessful until now, mostly because the number of engrafted hepatocytes required for clinical recovery can hardly be technically provided.5 Delivery of normal AGXT gene (coding for AGT) through different vectors is also in preclinical development.5 With RNAi drugs, it is likely that LT will disappear from transplantation strategies in the near future, thereby improving patient survival and quality of life. Importantly, it can be anticipated that the cost of these drugs will be unaffordable for some healthcare systems from emerging countries, where PH1 is more prevalent.1 The Transplant Community should be unified in asking pharmaceutical companies a solidarity strategy to include emerging countries in ongoing trials and drug supply when they will be available. This work was exempt from institutional review board approval.
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.
Kidney International Reports · 2021 · 0 citations · open access
POS-188 UNUSUAL PRESENTATION OF PRIMARY HYPEROXALURIA TYPE 1 AS POSTPARTUM ACUTE KIDNEY INJURY
AbstractPrimary hyperoxaluria type 1 (PH1) is a rare autosomal recessive disease caused by a mutation in the AGXT gene, resulting in deficiency of the alanineglyoxylate:aminotransferase enzyme. Often, the first sign is multiple recurrent nephrolithiasis, usually developped in second or third decade of life. This leads to renal interstitial and tubular damage, fibrosis, and end-stage renal disease (ESRD).
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.
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