DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for macroglobulinemia — 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 moduleMacroglobulinemia 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 macroglobulinemia 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
Bruton tyrosine kinase (BTK) — BTK 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 7h-pyrrolo[2,3-d]pyrimidin-4-yldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6VXQ · 1.4 Å · ligand N-{[4-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)phenyl]methyl}benzamide (RQS). Experimental structure, not a prediction.
What the evidence adds up to
In 587 patients with clearly defined Waldenström macroglobulinemia, median survival after treatment initiation was 87 months. Five adverse covariates were identified: age over 65 years, haemoglobin ≤11.5 g/dL, platelet count ≤100 × 10⁹/L, beta2-microglobulin >3 mg/L, and serum monoclonal protein >7.0 g/dL. Low-risk patients (27%) had none or one of these and advanced age; intermediate-risk (38%) had two adverse characteristics or only advanced age; high-risk (35%) had more than two. Five-year survival rates were 87%, 68%, and 36% respectively. The International Prognostic Scoring System for WM retained significance in subgroups defined by age and treatment type.
A retrospective study of ten Chinese patients over 60 years old treated with low-dose bortezomib and dexamethasone as first-line therapy reported an overall response rate of 80%: one complete response, one very good partial response, and six partial responses. Median time to response was 1.8 months. After a median follow-up of 36 months, all patients were alive and six had no disease progression. Estimated median time to progression was 39 months. Peripheral neuropathy occurred in six patients (60%) but did not cause bortezomib discontinuation. The authors concluded the regimen was effective and tolerable in this elderly group.
Two patients treated with long-term chlorambucil in 1963 were reported to have favourable responses, supporting earlier observations by Bayrd. A 1961 case report described two patients but provided no treatment outcome data. A 2019 review noted that treatment has evolved to include anti-CD20 monoclonal antibody-based combinations and BTK inhibitors, with continuous therapy now an option alongside fixed-duration chemoimmunotherapy. The 2025 state-of-the-art review states that WM has no cure, that treatment should be initiated only when symptoms appear, and that IgM level alone should not determine treatment. For relapsed or refractory disease, options include non-covalent BTK inhibitors, novel anti-CD20 antibodies, BCL-2 inhibitors, or more intensive chemotherapy; younger patients who have not responded to both chemoimmunotherapy and BTK inhibitors may be candidates for autologous stem cell transplant. Histological transformation to diffuse large B-cell lymphoma occurs in 2.4% to 11% of patients, with a median interval of 4.6 years.
What remains missing are prospective trials large enough to validate the prognostic scoring system in contemporary treatment contexts, randomised comparisons of the newer targeted agents against each other and against older regimens in defined molecular subgroups, and prospective data on long-term toxicity and quality of life with continuous BTK inhibitor therapy. Patient stratification by MYD88 and CXCR4 mutational status is now recommended but the optimal sequence of therapies for each subgroup is not established by randomised evidence.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Blood · 2009 · 416 citations · open access
International prognostic scoring system for Waldenström macroglobulinemia
AbstractRecently, many new drugs have been developed for the treatment of Waldenström macroglobulinemia (WM). To optimize the treatment according to the prognosis and to facilitate the comparison of trials, we developed an International Prognostic Scoring System for WM in a series of 587 patients with clearly defined criteria for diagnosis and for initiation of treatment. The median survival after treatment initiation was 87 months. Five adverse covariates were identified: advanced age (>65 years), hemoglobin less than or equal to 11.5 g/dL, platelet count less than or equal to 100 x 10(9)/L, beta2-microglobulin more than 3 mg/L, and serum monoclonal protein concentration more than 7.0 g/dL. Low-risk patients (27%) presented with no or 1 of the adverse characteristics and advanced age, intermediate-risk patients (38%) with 2 adverse characteristics or only advanced age, and high-risk patients (35%) with more than 2 adverse characteristics. Five-year survival rates were 87%, 68%, and 36%, respectively (P < .001). The ISSWM retained its prognostic significance in subgroups defined by age, treatment with alkylating agent, and purine analog. Thus, the ISSWM may provide a means to design risk-adapted studies. However, independent validation and new biologic markers may enhance its significance.
AbstractWaldenström macroglobulinemia (WM) is an uncommon lymphoma characterized by the infiltration of the bone marrow by clonal lymphoplasmacytic cells that produce monoclonal immunoglobulin M (IgM). The disease may have an asymptomatic phase, or patients may present with symptoms and complications resulting from marrow or other tissue infiltration, or from physicochemical or immunological properties of the monoclonal IgM. Diagnosis of WM has been clearly defined, and genetic testing for somatic mutation of MYD88L265P is a useful tool for differential diagnosis from other conditions. Specific criteria that define symptomatic disease that needs treatment offer clinical guidance. The treatment of WM has evolved rapidly, with treatment options that include anti-CD20 monoclonal antibody-based combinations and BTK inhibitors. The choice of therapy is based on the need for rapid disease control, presence of specific disease complications, and patient's age. With the use of BTK inhibitors, the use of continuous therapy has been introduced as another option over fixed-duration chemoimmunotherapy. In this review, we focus on different clinical scenarios and discuss treatment options, based on the available data.
AbstractMACROGLOBULINEMIA has been the subject of many reports and of several recent reviews.<sup>1-3</sup>Waldenström<sup>4</sup>first noted the occurrence of high molecular weight serum globulins as a prominent feature of certain blood dyscrasias. Despite the possibility of multiple etiologic factors, the well-defined biochemical abnormality and a generally recognized clinical picture lead one to the acceptance of macroglobulinemia as a disease entity. The disease is now considered to be a neoplasm of the reticuloendothelial system characterized by the proliferation of an abnormal cell type from which the macroglobulins probably originate. The abnormal cell has been variously described as "lymphocytoid," "lymphoid," and "plasmacytoid." It is our prime intention to report the results obtained with long-term administration of chlorambucil to our 2 patients with this condition, supporting the favorable observations reported by Bayrd.<sup>5</sup> <h3>Material and Methods</h3> We have had the opportunity to follow the clinical courses and serum protein patterns
American Journal of Clinical Pathology · 1961 · 12 citations
Macroglobulinemia: Report of Two Cases
AbstractJournal Article Macroglobulinemia: Report of Two Cases. Get access Michael E. Lamm, M.D. Michael E. Lamm, M.D. The Institute of Pathology, Western Reserve University, Cleveland 6, Ohio Search for other works by this author on: Oxford Academic Google Scholar American Journal of Clinical Pathology, Volume 35, Issue 1, 1 January 1961, Pages 53–65, https://doi.org/10.1093/ajcp/35.1.53 Published: 01 January 1961 Article history Received: 06 June 1960 Accepted: 01 August 1960 Published: 01 January 1961
European Journal Of Haematology · 2017 · 4 citations
Low‐dose bortezomib and dexamethasone as primary therapy in elderly patients with Waldenstrӧm macroglobulinemia
AbstractOBJECTIVE: This retrospective study was designed to determine the efficacy and safety of low-dose bortezomib and dexamethasone (lBD) in elderly Chinese patients with Waldenstrӧm macroglobulinemia (WM). METHODS: Ten patients with WM aged over 60 years received first-line treatment with lBD. RESULTS: The median age was 70 years (range, 61-77 years). The overall response rate was 80%, including 1 patient who achieved a complete response, 1 patient with very good partial response, and 6 patients with a partial response. Median time to response was 1.8 months after treatment with lBD. Six (60%) patients achieved a partial response, including 2 (20%) patients who had a more than 75% reduction in serum immunoglobulin M levels. A rapid reduction in paraprotein was observed in three patients who received plasmapheresis. After a median follow-up period of 36 months, all patients were still alive and six had no disease progression. The estimated median time to progression was 39 months (range, 15-60 months). The most common adverse events were anemia, thrombocytopenia, neuropathy, and neutropenia. Peripheral neuropathy was the most common non-hematological toxicity in six (60%) patients, but did not result in the discontinuation of bortezomib. CONCLUSIONS: Our findings show that lBD is an effective and tolerable treatment regimen for elderly patients with WM.
Mediterranean Journal of Hematology and Infectious Diseases · 2025 · 1 citations · open access
WALDENSTRÖM MACROGLOBULINEMIA - A STATE-OF-THE-ART REVIEW: PART 2- FOCUS ON THERAPY
AbstractThe diagnosis and treatment of Waldenstrom macroglobulinemia (WM) are the subjects of this two-part review, which aims to provide current and thorough knowledge of these topics. The first portion of the study, previously published, investigated the epidemiology, etiology, clinicopathological aspects, differential diagnosis, prognostic factors, and impact on WM-specific groups. Specifically, this second section examines both the standard consolidated method and the new therapeutic strategy to handle the complex topic of the treatment of WM. Key Points: WM has no cure, but therapies can improve survival. Treatment for WM/LPL patients should be initiated when they exhibit symptoms, and the IgM level should not determine WM treatment.Current guidelines suggest various initial personalized therapy treatments, typically chemoimmunotherapy (CIT) or BTK inhibitors (BTKi).Patients with WM can be put into three groups based on their MYD88 and CXCR4 mutational status: those with MYD88 mutations but no CXCR4 mutations (MYD88MUT/CXCR4WT), those with both MYD88 and CXCR4 mutations (MYD88MUT/CXCR4MUT) and those who do not have both MYD88 and CXCR4 mutations (MYD88WT/CXCR4WT).The objective of treatment is to alleviate symptoms and mitigate the risk of organ impairment.The timing of response evaluations, including BM, should be established on a case-by-case basis, informed by clinical and laboratory assessments.Patients with relapsed/refractory WM following chemotherapy and covalent Bruton tyrosine kinase inhibitors may choose non-covalent Bruton tyrosine kinase inhibitors, novel anti-CD20 monoclonal antibodies, BCL-2 inhibitors, or more intensive chemotherapy regimens.Patients who are younger and healthier and have not responded to both CIT and BTKi may be good candidates for an autologous stem cell transplant (ASCT).Second-generation anti-CD19 CAR T cells exhibit anti-WM activity in both in vitro and in vivo settings.From 2.4% to 11% of patients with WM undergo histological transformation, predominantly to diffuse large B-cell lymphoma (DLBCL). The median duration between diagnosis and transformation is 4.6 years.WM patients have a higher risk of secondary cancers.HSV and HZV prophylaxis may be beneficial for patients needing extensive treatment. Screening for Hepatitis B is necessary. Pneumocystis jiroveci prophylaxis is highly recommended. SARS-CoV- 2 and seasonal flu vaccines should be available to all WM patients.
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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