DeCure for Purine nucleoside phosphorylase deficiency
DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for purine nucleoside phosphorylase deficiency — 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 modulePurine nucleoside phosphorylase deficiency 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 purine nucleoside phosphorylase deficiency 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
purine nucleoside phosphorylase (PNP) — PNP 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 3r,4rdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 4EAR · 1.7 Å · ligand 2-amino-7-{[(3R,4R)-3-hydroxy-4-(hydroxymethyl)pyrrolidin-1-yl]methyl}-3,5-dihydro-4H-pyrrolo[3,2-d]pyrimidin-4-one (IM5). Experimental structure, not a prediction.
What the evidence adds up to
In 44 patients diagnosed with common variable immunodeficiency, screening for adenosine deaminase and purine nucleoside phosphorylase deficiency found no individuals with either enzyme defect, indicating that these deficiencies are not a frequent cause of that broader diagnosis. The same 1998 study notes that the clinical presentations of both enzyme deficiencies are widely variable and can include findings compatible with common variable immunodeficiency.
A 2021 report describes three neonates or infants who received a genetic diagnosis of purine nucleoside phosphorylase deficiency prenatally (two siblings) or early in life because of familial index cases. The disorder leads to combined immunodeficiency and neurological deficits such as developmental delay, ataxia, and motor impairment. The report is a case series of three patients who received upfront enzyme replacement via erythrocyte transfusions; no survival or response rates are given, and the abstract does not state outcomes.
A 1985 study tested urine from 16 patients on azathioprine therapy for deoxyguanosine and deoxyadenosine, markers of purine nucleoside phosphorylase and adenosine deaminase deficiency respectively. These abnormal nucleosides were not found in the azathioprine-treated patients or in 30 normal controls, but were easily detected in proven cases of PNP and ADA deficiency. The authors conclude there is a lack of in vivo inhibition of PNP and ADA by azathioprine.
A 2018 gene review states that PNP mutations cause nucleoside phosphorylase deficiency, resulting in defective T cell mediated immunity that can also affect B cell immunity and antibody responses. What remains missing are controlled trials of any intervention, validated biomarkers for stratifying patients by neurological versus immunological severity, and funding for natural history studies large enough to define endpoints for future therapies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Clinical and Diagnostic Laboratory Immunology · 1998 · 29 citations · open access
Adenosine Deaminase Deficiency and Purine Nucleoside Phosphorylase Deficiency in Common Variable Immunodeficiency
AbstractThe clinical presentations of adenosine deaminase deficiency and purine nucleoside phosphorylase deficiency are widely variable and include clinical and immunologic findings compatible with common variable immunodeficiency. The screening of 44 patients with common variable immunodeficiency failed to identify any individuals with deficiencies of these enzymes.
Journal of Clinical Immunology · 2021 · 9 citations · open access
Upfront Enzyme Replacement via Erythrocyte Transfusions for PNP Deficiency
AbstractPurine nucleoside phosphorylase (PNP) deficiency is a rare metabolic disorder leading to combined immunodeficiency (CID) and neurological deficits such as developmental delay, ataxia, and motor impairment. We report a series of three neonates/infants who had received a genetic diagnosis of PNP deficiency prenatally (P1 and P2, siblings) or early in life (P3) because of familial index cases
Agricultural and Biological Chemistry · 1991 · 6 citations · open access
Adenosine phosphorolyzing enzymes from microorganisms and ribavirin production by the application of the enzyme.
AbstractPurine nucleoside phosphorylase (PNPase), which can phosphorolyze various purine nucleosides, is widely distributed in prokaryotes and eukaryotes. This enzyme is classified into types according to substrate specificity. All the PNPases can phosphorolyze inosine and guanosine, and only some of these can also phosphorolyze adenosine or xanthosine. Zimmermanet al. reported that PNPases
British Journal of Clinical Pharmacology · 1985 · 0 citations · open access
Lack of inhibition of purine nucleoside phosphorylase and adenosine deaminase in patients treated with azathioprine.
AbstractDeficiency of the purine salvage enzymes purine nucleoside phosphorylase (PNP) and adenosine deaminase (ADA) are known causes of immunodeficiency. Evidence for inhibition of these enzymes was sought in 16 patients on azathioprine therapy by testing for deoxyguanosine (PNP deficiency) and deoxyadenosine (ADA deficiency) in urine using a novel phosphorescence method. These abnormal nucleosides were not found in urine of azathioprine treated patients or in 30 normal controls but were easily detected in urine from proven cases of PNP and ADA deficiency suggesting lack of in vivo inhibition of PNP and ADA by azathioprine.
Atlas of Genetics and Cytogenetics in Oncology and Haematology · 2018 · 0 citations · open access
PNP (Purine Nucleoside Phosphorylase)
AbstractThe purine nucleoside phosphorylase gene (PNP) encodes an enzyme which reversibly catalyzes the phosphorolysis of purine nucleosides. PNP is ubiquitously expressed in mammalian cells and tissues. PNP mutations cause nucleoside phosphorylase deficiency which result in defective T cell mediated immunity but can also affect B cell immunity and antibody responses.
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.
