DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for hyperprolinemia — 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 moduleHyperprolinemia 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 hyperprolinemia 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.
What the evidence adds up to
Hereditary hyperprolinemia is divided into type I (HPI), caused by a defect in proline oxidase, and type II (HPII), caused by a deficiency of Δ-1-pyrroline-5-carboxylate dehydrogenase. The clinical features of both types are unclear. For HPI, nephropathy, uncontrolled seizures, mental retardation and schizophrenia have been reported, but a benign phenotype without neurological problems has also been reported. A 2021 case report describes an HPI patient with short stature, carbohydrate-rich dietary preferences, and mild intellectual disability. For HPII, a 1974 report describes three siblings with high serum proline and urinary pyrroline-5-carboxylic acid who had no signs of associated anomalies, despite the condition being generally associated with mental retardation, seizures, and EEG anomalies.
The precise incidences of HPI and HPII are unknown. A 2014 Japanese survey identified only two cases of HPI and one case of HPII, suggesting the disease is very rare in Japan, consistent with earlier Western reports. The single Japanese HPII case was diagnosed in an individual with influenza-associated encephalopathy, which the authors suggest might indicate that HPII reduces the seizure threshold.
No drug treatment is mentioned in any of these abstracts. The 2014 paper presents diagnostic criteria based on plasma proline level with or without urinary P5C measurement. The 2021 case identified a homozygous p.T466M mutation in the PRODH gene. What is missing is any clinical trial data, any tested intervention, any patient stratification beyond the two known genotypes, and any funding for systematic natural history studies that could clarify which patients, if any, develop symptoms.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Pediatrics International · 2014 · 44 citations · open access
Biochemical and clinical features of hereditary hyperprolinemia
AbstractThere are two classifications of hereditary hyperprolinemia: type I (HPI) and type II (HPII). Each type is caused by an autosomal recessive inborn error of the proline metabolic pathway. HPI is caused by an abnormality in the proline-oxidizing enzyme (POX). HPII is caused by a deficiency of Δ-1-pyrroline-5-carboxylate (P5C) dehydrogenase (P5CDh). The clinical features of HPI are unclear. Nephropathy, uncontrolled seizures, mental retardation or schizophrenia have been reported in HPI, but a benign phenotype without neurological problems has also been reported. The clinical features of HPII are also unclear. In addition, the precise incidences of HPI and HPII are unknown. Only two cases of HPI and one case of HPII have been identified in Japan through a questionnaire survey and by a study of previous reports. This suggests that hyperprolinemia is a very rare disease in Japan, consistent with earlier reports in Western countries. The one case of HPII found in Japan was diagnosed in an individual with influenza-associated encephalopathy. This suggests that HPII might reduce the threshold for convulsions, thereby increasing the sensitivity of individuals with influenza-associated encephalopathy. The current study presents diagnostic criteria for HPI and HPII, based on plasma proline level, with or without measurements of urinary P5C. In the future, screening for HPI and HPII in healthy individuals, or patients with relatively common diseases such as developmental disabilities, epilepsy, schizophrenia or behavioral problems will be important.
Human Genome Variation · 2021 · 12 citations · open access
Hyperprolinemia type I caused by homozygous p.T466M mutation in PRODH
AbstractHyperprolinemia type I (HPI) is an autosomal recessive metabolic disorder caused by defects in proline oxidase. We herein describe a case of a patient with HPI and harboring the NM_016335.4 (PRODH_v001):c.1397 C > T (p.T466M) mutation and polymorphisms in the PRODH gene, as detected by plasma amino acid analysis and Sanger sequencing. The patient presented with short stature, carbohydrate-rich dietary preferences, and mild intellectual disability that was suggestive of a neurodevelopmental or learning disorder.
Acta geneticae medicae et gemellologiae · 1974 · 0 citations · open access
Asymptomatic Type II Hyperprolinemia Associated with Hyperglycinemia in Three Siblings
AbstractType II hyperprolinemia is a rare metabolic disorder associated with mental retardation, seizures, and EEG anomalies. The authors describe a Sicilian family, detected screening for aminoacidopathies by the method of Scriver, in which three siblings have high levels of serum proline and urinary pyrroline-5-carboxylic acid, without any signs of associated anomalies.
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.
