DeCure for Severe combined immunodeficiency due to LCK deficiency
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for severe combined immunodeficiency due to LCK deficiency — 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 moduleSevere combined immunodeficiency due to LCK deficiency 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 severe combined immunodeficiency due to lck deficiency 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
LCK proto-oncogene, Src family tyrosine kinase (LCK) — LCK 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 6-methoxypyrazolo[1,5-a]pyridine-3-carbonyldrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 6PDJ · 1.81 Å · ligand N-{4-[(6-methoxypyrazolo[1,5-a]pyridine-3-carbonyl)amino]-3-methylphenyl}-1-methyl-1H-indazole-3-carboxamide (ODJ). Experimental structure, not a prediction.
What the evidence adds up to
The abstracts provided do not contain any original research on severe combined immunodeficiency due to LCK deficiency. No patients with LCK deficiency are described, no treatments are tested, and no outcomes are reported. The papers cover common variable immunodeficiency disorders, PRKCD deficiency, immunoglobulin therapy, and other primary immunodeficiencies such as X-linked SCID and IKK2 deficiency. None of these studies involve LCK.
The 2013 paper on PRKCD deficiency reports a single patient from a consanguineous family with recurrent infections and severe lupus-like autoimmunity, showing progressive decrease of CD19+ B cells and defective class switch. The 2020 entry on IKK2 deficiency notes life-threatening infections in infancy with hypogammaglobulinemia or agammaglobulinemia but normal T and B cell numbers. These are distinct conditions with different genetic causes.
For severe combined immunodeficiency due to LCK deficiency, there is no evidence from these abstracts to support any specific treatment, including immunoglobulin therapy or gene therapy. The 1997 and 2002 reviews discuss gene therapy and stem cell transplants for other SCID forms, but not for LCK deficiency. What is still missing is any published clinical data on LCK-deficient patients, a defined natural history, and any trial of targeted therapy or gene correction.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
British Journal of Haematology · 2009 · 392 citations · open access
Update in understanding common variable immunodeficiency disorders (CVIDs) and the management of patients with these conditions
AbstractThe common variable immunodeficiency disorders are a mixed group of heterogeneous conditions linked by lack of immunoglobulin production and primary antibody failure. This variability results in difficulty in making coherent sense of either immunopathogenesis or the role of various genetic abnormalities reported in the literature. The recent attempt to collate the varied complications in these conditions and to define particular clinical phenotypes has improved our understanding of these diseases. Once refined and confirmed by other studies, these definitions will facilitate improved accuracy of prognosis and better management of clinical complication. They may also provide a method of analysing outcomes as related to new immunopathological and genetic findings.
B-cell deficiency and severe autoimmunity caused by deficiency of protein kinase C δ
AbstractPrimary B-cell disorders comprise a heterogeneous group of inherited immunodeficiencies, often associated with autoimmunity causing significant morbidity. The underlying genetic etiology remains elusive in the majority of patients. In this study, we investigated a patient from a consanguineous family suffering from recurrent infections and severe lupuslike autoimmunity. Immunophenotyping revealed progressive decrease of CD19(+) B cells, a defective class switch indicated by low numbers of IgM- and IgG-memory B cells, as well as increased numbers of CD21(low) B cells. Combined homozygosity mapping and exome sequencing identified a biallelic splice-site mutation in protein C kinase δ (PRKCD), causing the absence of the corresponding protein product. Consequently, phosphorylation of myristoylated alanine-rich C kinase substrate was decreased, and mRNA levels of nuclear factor interleukin (IL)-6 and IL-6 were increased. Our study uncovers human PRKCD deficiency as a novel cause of common variable immunodeficiency-like B-cell deficiency with severe autoimmunity.
An Update on the Use of Immunoglobulin for the Treatment of Immunodeficiency Disorders
AbstractFor patients with significant antibody deficiencies, immunoglobulin therapy is the mainstay of treatment as it significantly reduces both the frequency and severity of infections. The formulations and delivery methods of immunoglobulin have evolved over time, and continued improvements have allowed for increased access to this effective medication. This review is an update on the current status of immunoglobulin therapy in immunodeficiency disorders, and discusses the mechanisms, forms and dosing, and indications for immunoglobulin replacement.
Current Opinion in Pediatrics · 1997 · 15 citations
The molecular basis and treatment of primary immunodeficiency disorders
AbstractOver the past decade, a number of important advances have been made in the molecular characterization and the treatment of the primary immunodeficiency disorders. These advances include identification of the abnormal genes responsible for such syndromes as X-linked severe combined immune deficiency, several forms of autosomal severe combined immune deficiency, X-linked and autosomal agammaglobulinemia, Wiskott-Aldrich syndrome, and other primary immunodeficiency disorders. In the past year, the biologic functions of the abnormal gene products responsible for these syndromes have been better defined, and new molecular defects that lead to primary immunodeficiency disorders have also been reported. This better understanding of the molecular basis of the primary immunodeficiency disorders has led to improvement of established therapies, such as gene product replacement and stem cell transplants, and to new treatment strategies, such as gene therapy.
AbstractSevere combined immunodeficiency is one of the most common causes of primary immunodeficiencies in humans. Molecular biological techniques have allowed new, therapeutically useful treatments for these diseases to be introduced into clinical practice. This review will focus on the molecular basis and new treatments for X-linked severe combined immunodeficiency.
Majalah Kesehatan Pharmamedika · 2011 · 0 citations
Defisiensi Antibodi Primer dan Hubungannya dengan Kelainan Kulit
AbstractPrimary antibody deficiency is the most abnormality found in primary immunodeficiency. It is caused by function defect and cell B development which antibody production. it is commonly found on baby and children, except common variable immunodeficiency (CVID) which mostly on adult. Cutaneous manifestaion caused by primary antibody deficiency, not specific, and not as many as other defeciency like cell T deficiency. Cutaneous abnormality caused by bacterial infection is the main problem beside atopy and autoimmune disease. Immunoglobulin replacement therapy has a important role in primer antibody deficiency management.
Severe combined immunodeficiency due to IKK2 deficiency
AbstractOpe n Pe e r Re v ie w on Qe ios Ope n Pe e r Re v ie w on Qe ios Severe combined immunodeficiency due to IKK2 deficiency INSERM Source INSERM.(1999).Orphanet: an online rare disease and orphan drug data base.Severe combined immunodeficiency due to IKK2 deficiency.ORPHA:397787 Severe combined immunodeficiency due to IKK2 deficiency is a rare, genetic form of primary immunodeficiency characterized by life-threatening bacterial, fungal and viral infections with the onset in infancy, and failure to thrive.T ypically, hypogammaglobulinemia or agammaglobulinemia and normal levels of T and B cells are present.
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.
