DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lymphoproliferative syndrome 1 — 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 moduleLymphoproliferative syndrome 1 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 lymphoproliferative syndrome 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
IL2 inducible T cell kinase (ITK) — ITK 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…
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RCSB Protein Data Bank · entry 4HCU · 1.43 Å · ligand 3-{4-amino-1-[(3R)-1-propanoylpiperidin-3-yl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}-N-[4-(propan-2-yl)phenyl]benzamide (13L). Experimental structure, not a prediction.
What the evidence adds up to
X-linked lymphoproliferative disease (XLP) is a rare and often fatal primary immunodeficiency characterised by a dysregulated immune response, most commonly to Epstein-Barr virus infection. The defective gene, identified by 2003, is SAP-SLAM-associated protein, an adapter molecule required for appropriate function of SLAM-related receptors. Clinical diagnosis is difficult due to a varied phenotype, and protein and genetic assays are used for definitive diagnosis. The mutated gene was cloned within the year prior to a 1993 review.
In a 2012 study of posttransplant lymphoproliferative disorders after heart transplantation, four patients received intravenous rituximab at 375 mg/m² weekly for 6 ± 2 weeks. The overall response rate was 75%, with three complete responses in patients whose tumours were CD20 positive and one case of progressive disease in a CD20-negative patient. The authors stated rituximab should be considered first-line therapy for CD20-positive posttransplant lymphoproliferative disorders.
A 2023 case report describes a 71-year-old woman with adult-onset Still’s disease who developed a primary hepatic other iatrogenic immunodeficiency-associated lymphoproliferative disorder (OIIA-LPD) after only five months of methotrexate therapy (6 mg per week), alongside prednisone and later tocilizumab. A solitary liver tumour measuring 37 × 32 mm was detected, and three months later it had grown to 7 cm in diameter, with a calculated doubling time of 33 days. Despite withdrawing methotrexate for six weeks, the tumour continued to grow, and the patient was referred to haematology. In previously reported cases of methotrexate-associated lymphoproliferative disorders of hepatic origin, the average duration of methotrexate administration was 7.3 years (range 2–13 years).
What remains missing are prospective trials testing specific drugs for XLP, adequate funding for such trials given the rarity of the condition, and reliable patient stratification methods that account for the varied clinical phenotypes and the different contexts in which lymphoproliferative disorders arise.
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 Pediatrics and Adolescent Medicine · 1993 · 24 citations
X-linked Lymphoproliferative Disease
AbstractThe disease discussed in this chapter was discovered 30 yr ago at the autopsy table by a young and very inquisitive pathologist. Within the past year, the mutated gene central to this condition has been cloned and studies are underway to elucidate its normal immunologic function. This review summarizes our present state of knowledge of X-linked lymphoproliferative disease (XLP).
Expert Review of Molecular Diagnostics · 2003 · 24 citations
Pathogenesis and diagnosis of X-linked lymphoproliferative disease
AbstractX-linked lymphoproliferative syndrome (XLP) is a rare, often fatal, primary immunodeficiency that has profound and damaging effects on the immune system of affected individuals. It is characterized by a dysregulated immune response, most commonly to Epstein-Barr viral infection. The defective gene in this syndrome has been identified as SAP-SLAM (signaling lymphocyte activation molecule)-associated protein. It is an adapter molecule that is required for appropriate function of the SLAM-related receptors. There is now a greater understanding of the molecular associations and cellular pathogenesis of SAP and this review will summarize the most recent findings. Clinically, XLP may be difficult to diagnose as a result of its varied clinical phenotype, and protein and genetic assays are currently used to make a definitive diagnosis. With the advances in gene analysis and genomics technology, it is likely that better and more rapid diagnostic techniques will become available.
Experimental and Clinical Transplantation · 2012 · 5 citations
Usefulness and Limitations of Rituximab in Managing Patients With Lymphoproliferative Disorder After Heart Transplantation
AbstractPosttransplant lymphoproliferative disorders remain an uncommon complication of heart transplant with a high mortality rate reported after conventional therapies. Four patients with posttransplant lymphoproliferative disorders, of whom 3 were CD20 positive, received intravenous dosages of rituximab, 375 mg/m(2), weekly, for 6 ± 2 weeks. The overall response rate was 75% with 3 complete responses (CD20 positive) and 1 case of progressive disease (CD20 negative). Rituximab should be considered as a first-line therapy for patients with CD20 positive posttransplant lymphoproliferative disorders.
AbstractRapid advances in our understanding of the biology and pathology of lymphoproliferative disorders, permitted mainly by new diagnostic tools, constantly change our approach to this heterogenous group of disorders. In this review of the more indolent subgroup of lymphoproliferative disorders, some of the recent advances are highlighted, and treatment options discussed.
Journal of Medical Cases · 2023 · 3 citations · open access
Primary Hepatic Other Iatrogenic Immunodeficiency-Associated Lymphoproliferative Disorders After Methotrexate Therapy
AbstractPrior reports described cases of lymphoproliferative diseases occurring after methotrexate (MTX) administration, which are called methotrexate-associated lymphoproliferative disorders (MTX-LPDs). It has become clear that these lymphoproliferative diseases also occur following treatment with other immunosuppressive drugs, and they have been termed as other iatrogenic immunodeficiency-associated lymphoproliferative disorders (OIIA-LPDs). In most of these cases, the duration of immunosuppressive drugs is very long, on the order of years. In the present study, we evaluated the development of lymphoproliferative disease despite the short duration of immunosuppressive treatment and determined the tumor doubling time. A 71-year-old woman was diagnosed with adult-onset Still’s disease. The patient was administered prednisone 30 mg per day starting on February 25, 2022 and MTX 6 mg per week starting 2 weeks later. Because she was a hepatitis B virus (HBV) carrier, nucleic acid analog therapy was also started to prevent HBV activation. Eight weeks later, biweekly tocilizumab was started. After 5 months of MTX administration, a solitary liver tumor measuring 37 × 32 mm 2 was detected. Three months later, repeat computed tomography revealed that the liver tumor had grown rapidly to 7 cm in diameter. We considered the possibility of OIIA-LPDs and stopped MTX therapy. Biopsy specimens of the liver tumor exhibited lymphocyte proliferation, which was consistent with OIIA-LPDs. The doubling time for tumor growth was 33 days. Despite withdrawing MTX for 6 weeks, the tumor continued to grow, and thus, the patient was referred to the hematology unit. In previously reported cases of MTX-LPDs of hepatic origin, the average duration of MTX administration was 7.3 (2 - 13) years. This report describes a primary hepatic OIIA-LPDs-associated tumor that rapidly increased in size after an extremely short period of MTX administration. J Med Cases. 2023;14(8):282-288 doi: https://doi.org/10.14740/jmc4135
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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