DeCure's autonomous Rare AI scientist is researching a drug-repurposing hypothesis for leukocyte adhesion deficiency type II — 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 type II 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 type ii 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.
What the evidence adds up to
In a canine model of leukocyte adhesion deficiency, ex vivo retroviral gene therapy targeting the CD18 adhesion molecule produced therapeutic levels of CD18-positive leukocytes in 6 of 11 treated dogs. Conditioning with either 200 cGy total body irradiation or 10 mg/kg busulfan allowed long-term engraftment without post-transplantation immunosuppression. The percentage of CD18-positive cells in peripheral blood rose progressively over 6 to 8 months, reaching 1.26% to 8.37% at one-year follow-up, and this was enough to reverse or moderate the severe phenotype. Insertion sites were polyclonal. No human trial data are reported in these abstracts.
Anti-adhesion therapy more broadly has been tested in clinical trials for inflammatory diseases, but the results have been disappointing. A 2005 review notes that many such trials yielded disappointing outcomes and questions whether the animal models used are suitable for predicting human efficacy. A 1997 review of anti-adhesion therapy in experimental animal models discusses its potential and limitations but does not report any successful human application.
Leukocyte adhesion deficiency type I is described as an extremely serious and rare congenital immunodeficiency, typically diagnosed in childhood, with recurrent bacterial infections from the neonatal period. A 2014 case report emphasises that early diagnosis in neonates allows early definitive treatment with promising results, but gives no specific survival or response numbers. The abstracts contain no data on any drug treatment for leukocyte adhesion deficiency type II specifically.
What is still missing: a human trial of gene therapy for leukocyte adhesion deficiency, any drug that has shown efficacy in the type II form of the disease, and a clear understanding of why anti-adhesion strategies that work in animal models fail in human inflammatory diseases. Patient stratification and timing of intervention remain unaddressed.
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 · 2006 · 43 citations · open access
Correction of the disease phenotype in canine leukocyte adhesion deficiency using ex vivo hematopoietic stem cell gene therapy
AbstractCanine leukocyte adhesion deficiency (CLAD) represents the canine counter-part of the human disease leukocyte adhesion deficiency (LAD). Defects in the leukocyte integrin CD18 adhesion molecule in both CLAD and LAD lead to recurrent, life-threatening bacterial infections. We evaluated ex vivo retroviral-mediated gene therapy in CLAD using 2 nonmyeloablative conditioning regimens--200 cGy total body irradiation (TBI) or 10 mg/kg busulfan--with or without posttransplantation immunosuppression. In 6 of 11 treated CLAD dogs, therapeutic levels of CD18(+) leukocytes were achieved. Conditioning with either TBI or busulfan allowed long-term engraftment, and immunosuppression was not required for efficacy. The percentage of CD18(+) leukocytes in the peripheral blood progressively increased over 6 to 8 months after infusion to levels ranging from 1.26% to 8.37% at 1-year follow-up in the 6 dogs. These levels resulted in reversal or moderation of the severe CLAD phenotype. Linear amplification-mediated polymerase chain reaction assays indicated polyclonality of insertion sites. These results describe ex vivo hematopoietic stem cell gene transfer in a disease-specific, large animal model using 2 clinically applicable conditioning regimens, and they provide support for the use of nonmyeloablative conditioning regimens in preclinical protocols of retroviral-mediated gene transfer for nonmalignant hematopoietic diseases such as LAD.
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.
Journal of Clinical Neonatology · 2014 · 5 citations · open access
Unusual neonatal presentation of type I leukocyte adhesion deficiency
AbstractLeukocyte adhesion deficiency type I is an extremely serious and rare form of congenital immunodeficiency with recurrent episodes of infection since neonatal period. It is usually diagnosed in childhood, but if diagnosed early in neonatal period then definitive treatment can be instituted early with promising results. High index of suspicion is necessary to diagnose this condition in neonates. Neonate may present with serious bacterial infections with a leukemoid reaction.
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.
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.
