DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for leukocyte adhesion deficiency 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 moduleLeukocyte adhesion deficiency 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 leukocyte adhesion deficiency 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
integrin subunit beta 2 (ITGB2) — ITGB2 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 apo structuredrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7USL · 2.7 Å · ligand none (apo structure). Experimental structure, not a prediction.
What the evidence adds up to
Leukocyte adhesion deficiency 1 is a heritable disease caused by heterogeneous mutations in the β subunit common to the LFA-1, Mac-1, and p150,95 family of leukocyte adhesion proteins. Patients suffer severe recurrent bacterial and fungal infections of soft tissues, primarily skin and mucous membranes. Infected necrotic lesions contain few leukocytes despite chronic leukocytosis. The disease is rare, and its characterisation in the 1980s helped reveal the molecular mechanisms of leukocyte migration across blood vessels.
Anti-adhesion therapy — blocking the leukocyte-endothelial adhesive interactions that are defective in LAD-1 — has been tested in experimental animal models and clinical trials for inflammatory diseases. The rationale is that controlled inhibition of the adhesion cascade could suppress inflammatory and immune responses. However, many clinical trials of anti-adhesion therapy have yielded disappointing outcomes. Animal models have raised questions about whether blocking adhesion is suitable for treating certain inflammatory diseases.
No clinical trial of anti-adhesion therapy specifically for leukocyte adhesion deficiency 1 has been reported in these abstracts. The 1997 review discusses only experimental animal models and the limitations of the approach. The 2005 review notes that effective anti-adhesion therapy requires understanding the underlying mechanisms and time lines of leukocyte recruitment in each affected tissue and disease.
What is still missing is any clinical trial testing anti-adhesion therapy in LAD-1 patients, a clear understanding of whether blocking the already deficient adhesion pathway could be beneficial or harmful, and the patient stratification and trial design needed to evaluate such an approach in a rare disease.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Microcirculation · 2005 · 18 citations
Therapeutic Intervention in Inflammatory Diseases: A Time and Place for Anti‐Adhesion Therapy
AbstractThe recruitment of leukocytes from the blood into tissue is central to the development and maintenance of the majority of inflammatory diseases. This multistep process requires a series of leukocyte-endothelial adhesive interactions, involving several families of adhesion molecules. Molecules that block these interactions have been targeted as potential therapeutic treatments for acute and chronic inflammatory diseases. However, many of the anti-adhesion therapy clinical trials have yielded disappointing outcomes. This review discusses some of the animal models that raise questions about the suitability of anti-adhesion therapy to treat certain inflammatory diseases. The authors suggest that it is crucial to understand the underlying mechanisms and time lines of leukocyte recruitment in each affected tissue and inflammatory disease to develop more effective anti-adhesion therapy.
Anti-adhesion therapy: Its current status and perspective.
AbstractIn acute inflammatory responses, a series of adhesive interactions occurs consecutively between circulating leukocytes and vascular endothelial cells of inflamed tissues. Recent studies have demonstrated that this leukocyte-endothelial adhesion cascade is mediated by a number of adhesion molecules and that the controlled inhibition of the adhesion cascade results in significant suppression of inflammatory and/or immune responses. Here we summarize our own attempts in such antiadhesion therapy in various experimental animal models and discuss its potential, limitation and future perspective.
Japanese Journal of Clinical Immunology · 1988 · 0 citations · open access
Molecular analysis of human leukocyte adhesion deficiency.
AbstractThe normal response of the immune system to infections of the skin or mucosal tissues requires the ability of peripheral blood leukocytes to mobilize to the site of infection. In a classical inflammatory reaction, neutrophils and monocytes migrate in response to chemotactic factors released at the infection site. However, until recently, the molecular mechanisms which enable leukocytes to migrate across blood vessels have been largely unknown. These mechanisms have been elucidated, in part, by the characterization of a recently defined disease called human leukocyte adhesion deficiency (LAD). Patients with this heritable disease suffer from severe recurrent bacterial and fungal infections of soft tissues, primarily skin and mucous membranes. Infected, necrotic lesions in these patients contain few leukocytes despite the observation that these patients have chronic leukocytosis. In the early 1980's, several laboratories demonstrated that this disease is due to a cell surface deficiency of the LFA-1, Mac-1, and p150, 95 family of leukocyte adhesion proteins. More recently we have shown that LAD is due to heterogenous mutations in the β subunit common to the all three of these leukocyte glycoproteins. Although LAD is a rare disease, the analysis of this disease has greatly increased our understanding of the biology of the leukocyte adhesion proteins and the molecular mechanisms involved in the immune response to infections of the skin.
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.
