DeCure for X-Linked Combined Immunodeficiency Diseases
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for X-Linked Combined Immunodeficiency Diseases — 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 moduleX-Linked Combined Immunodeficiency Diseases 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 x-linked combined immunodeficiency diseases 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
interleukin 2 receptor subunit gamma (IL2RG) — IL2RG 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 cysdrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 5M5E · 2.3 Å · ligand CYSTEINE (CYS). Experimental structure, not a prediction.
What the evidence adds up to
X-linked severe combined immunodeficiency in dogs is caused by a 4-base-pair deletion in the first exon of the IL-2 receptor gamma chain gene, which prevents production of a functional protein. This makes the canine disease a true homologue of human X-linked SCID. No treatment data for that condition appear in these abstracts.
A phase 1 trial of sunitinib combined with antiretroviral therapy in HIV-positive cancer patients enrolled 19 evaluable subjects. Patients not on ritonavir-based HAART tolerated standard 50 mg/day sunitinib with no dose-limiting toxicity. Those on ritonavir-based HAART experienced a dose-limiting toxicity at 37.5 mg, and three of five patients had grade 3 neutropenia, an uncommon toxicity for sunitinib. No patient achieved a response; ten had stable disease, eight with prolonged stability. Efavirenz increased exposure of the active metabolite N-desethyl sunitinib, while ritonavir decreased it. Hand-foot syndrome correlated with higher steady-state trough sunitinib concentrations. The authors suggest reducing sunitinib to 37.5 mg in patients receiving ritonavir.
A review chapter on X-linked lymphoproliferative diseases describes them as primary immunodeficiencies with recurrent infections, autoimmune disease, and malignancies. It lists prophylactic anti-infectives, haematopoietic stem cell transplantation, and gene therapy as therapeutic options, but provides no trial results, response rates, or survival data from these abstracts.
What is still missing: no clinical trial has tested any drug specifically for X-linked SCID or X-linked lymphoproliferative disease in these abstracts. The sunitinib study was in HIV-positive cancer patients, not in primary immunodeficiency. No data exist on patient stratification, biomarker-driven dosing, or funding for a dedicated trial in these rare immunodeficiencies.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Genomics · 1994 · 112 citations · open access
IL-2Rγ Gene Microdeletion Demonstrates That Canine X-Linked Severe Combined Immunodeficiency Is a Homologue of the Human Disease
AbstractX-linked severe combined immunodeficiency (SCID) is characterized by profound defects in cellular and humoral immunity and, in humans, is associated with mutations in the gene for the gamma chain of the IL-2 receptor (IL-2R gamma). We have examined this gene in a colony of dogs established from a single X-linked SCID carrier female. Affected dogs have a 4-bp deletion in the first exon of the IL-2R gamma gene, which precludes the production of a functional protein, demonstrating that the canine disease is a true homologue of human X-linked SCID.
A phase 1/pharmacokinetic study of sunitinib in combination with highly active antiretroviral therapy in human immunodeficiency virus‐positive patients with cancer: AIDS Malignancy Consortium trial AMC 061
AbstractBACKGROUND: The treatment of non-acquired immunodeficiency syndrome-defining cancers may be complicated by drug interactions between highly active antiretroviral therapy (HAART) and chemotherapy. This trial is the first by the AIDS Malignancy Consortium to assess targeted therapies and HAART in human immunodeficiency virus-positive patients (ClinicalTrials.gov identifier: NCT00890747). METHODS: In a modified phase 1 study of sunitinib, patients were stratified into 2 treatment arms based on whether they were receiving therapy with ritonavir, a potent CYP3A4 inhibitor. Patients in treatment arm 1 (non-ritonavir HAART) received standard sunitinib dosing (50 mg/day). Treatment arm 2 (ritonavir-based HAART) used a phase 1, 3 + 3 dose escalation design (from 25 mg/day to 50 mg/day). Cycles were comprised of 4 weeks on treatment followed by a 2-week break (6 weeks total). The pharmacokinetics of sunitinib and its active metabolite (N-desethyl sunitinib) were assessed. RESULTS: Nineteen patients were enrolled and were evaluable. Patients on treatment arm 1 tolerated treatment with no dose-limiting toxicity observed. In treatment arm 2, a dose-limiting toxicity was experienced at a dose of 37.5 mg, and an additional 3 of 5 patients experienced grade 3 neutropenia (toxicity graded as per National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]), an uncommon toxicity of sunitinib. No patient achieved a response, but 10 patients had stable disease, including 8 with prolonged disease stability. Efavirenz, a potent inducer of CYP3A4, resulted in increased exposure of N-desethyl sunitinib, whereas ritonavir caused decreased exposure of the metabolite. Hand-foot syndrome was associated with higher steady-state trough concentrations of sunitinib. CONCLUSIONS: Patients receiving non-ritonavir-based HAART regimens tolerated standard dosing of sunitinib. Patients receiving ritonavir-based therapy who were treated with a dose of 37.5 mg/day experienced higher toxicities. Dose reductions of sunitinib to 37.5 mg may be warranted in patients receiving ritonavir.
Oxford University Press eBooks · 2013 · 0 citations
X-Linked Lymphoproliferative Diseases
AbstractAbstract Primary immunodeficiency diseases are inherited disorders that affect human adaptive and innate immunity. In most cases, affected individuals experience recurrent infections, but they may also suffer from autoimmune diseases and malignancies. This chapter focuses on X-Linked Lymphoproliferative Diseases,including the historic and scientific background, clinical presentations, immunologic characteristics, and the molecular/genetic underpinnings. Where appropriate, diagnostic tools and therapeutic options are outlined -- from prophylactic anti-infective measures to hematopoietic stem cell transplantation and gene 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.
