DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for lymphoproliferative syndrome 2 — 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 moduleLymphoproliferative syndrome 2 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 lymphoproliferative syndrome 2 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
CD27 molecule (CD27) — CD27 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 2pedrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8DS5 · 1.926 Å · ligand NONAETHYLENE GLYCOL (2PE). Experimental structure, not a prediction.
What the evidence adds up to
In a 2012 series of four heart transplant recipients with posttransplant lymphoproliferative disorder, three patients whose tumours were CD20 positive received intravenous rituximab at 375 mg/m² weekly for a mean of six weeks. The overall response rate was 75%, with three complete responses among the CD20 positive cases and one case of progressive disease in a patient whose tumour was CD20 negative. The authors concluded that 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 after only five months of methotrexate therapy, far shorter than the average 7.3 years reported in prior hepatic methotrexate-associated lymphoproliferative disorder cases. The liver tumour grew from 37 × 32 mm to 7 cm in diameter over three months, with a calculated doubling time of 33 days. Despite withdrawal of methotrexate for six weeks, the tumour continued to grow, and the patient was referred to haematology.
A 2025 case report describes a patient with methotrexate-associated lymphoproliferative disorder whose disease initially responded to methotrexate withdrawal but later showed progressive lymphadenopathy. Because of multiple comorbidities and poor functional status, cytotoxic chemotherapy was not an option. The care team used a combination of rituximab and brentuximab, a regimen not well described in the lymphoma literature, and the patient achieved a brief but complete remission.
The evidence for rituximab in posttransplant lymphoproliferative disorder rests on a very small series with no control group, and its efficacy in CD20 negative disease is absent. The rapid tumour growth after short methotrexate exposure in the 2023 case highlights that withdrawal of the offending drug does not always halt progression. The 2025 case shows that even a complete remission from a novel biologic combination can be brief. What is missing are prospective trials with adequate sample sizes, standardised definitions of when drug withdrawal alone is sufficient versus when additional therapy is needed, and stratification by CD20 status and histological subtype.
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 · 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.
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
Treatment of Methotrexate-Associated Lymphoproliferative Disorder With Biological Therapies
AbstractLymphoproliferative disorders may arise as a complication of immunosuppressant medications, such as methotrexate. This case report describes a patient who developed a rare subtype of methotrexate-associated lymphoproliferative disorder. His disease initially responded well to the withdrawal of methotrexate. However, several months after diagnosis, surveillance testing revealed progressive lymphadenopathy. Owing to his multiple comorbidities and resultant poor baseline functional status, he was not a candidate for cytotoxic chemotherapy. Based on key histopathological characteristics of his rare disorder, his care team devised an alternative therapy, consisting of rituximab and brentuximab, a unique protocol that is not well-described in the lymphoma literature. The patient achieved a brief but complete remission from this therapy.
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.
