DeCure for Combined immunodeficiency due to moesin deficiency
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for combined immunodeficiency due to moesin 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 moduleCombined immunodeficiency due to moesin 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 combined immunodeficiency due to moesin 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
moesin (MSN) — MSN 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 2-hydroxy-1,1-dihydroxymethyl-ethylaminodrag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 8CIR · 1.85 Å · ligand 2-[3-(2-HYDROXY-1,1-DIHYDROXYMETHYL-ETHYLAMINO)-PROPYLAMINO]-2-HYDROXYMETHYL-PROPANE-1,3-DIOL (B3P). Experimental structure, not a prediction.
What the evidence adds up to
Immunoglobulin replacement therapy is the standard treatment for antibody deficiencies, and two review articles describe its use in primary immunodeficiency generally. One 2014 review states that immunoglobulin significantly reduces both the frequency and severity of infections in patients with significant antibody deficiencies. A 2016 review adds that it protects against serious upper and lower respiratory tract infections, improves pulmonary function, and increases quality of life. A 1983 paper on primary immunoglobulin deficiency and haematological disorders reports that infections were reduced in all six patients treated with gammaglobulin. None of these papers mention moesin deficiency specifically.
The only abstract that directly addresses moesin deficiency is a 2018 case report of a single male proband. Exome sequencing identified a novel hemizygous X-linked missense mutation in the MSN gene (c.511C>T p.Arg171Trp), inherited from his non-symptomatic carrier mother. Western blot showed absence of moesin protein in the proband’s lymphocytes, and qPCR confirmed significantly lower MSN mRNA expression in whole blood (P = 0.02) and lymphocytes (P = 0.01) compared to a healthy control. The proband had recurrent bacterial and Varicella zoster infections in childhood and persistent lymphopaenia into early adulthood, and had remained undiagnosed until age 24. No treatment outcome for this patient is reported in the abstract.
Two other abstracts are irrelevant to moesin deficiency: one covers major histocompatibility complex class II deficiency, a different primary immunodeficiency, and another discusses immunoglobulin choice in Russian clinical practice without reference to moesin. No abstract provides any data on immunoglobulin therapy specifically in moesin-deficient patients. What is missing is any clinical trial, case series, or even a single treated patient with moesin deficiency whose response to immunoglobulin has been documented. The evidence for benefit in this specific condition is therefore absent, not merely incomplete.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Immunotherapy · 2014 · 62 citations · open access
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.
The use of Immunoglobulin Therapy in Primary Immunodeficiency Diseases
AbstractImmunoglobulin therapy represents a lifesaving intervention for many patients with primary immunodeficiency (PID). Antibody defects represent approximately half of the well-known PIDs requiring immunoglobulin replacement therapy. Following immunoglobulin therapy in PID patients, protection against serious upper and lower respiratory tract infections and pulmonary function improves which leads to an increase in the quality of life of these patients. Successful treatment of PID patients depends on the type of immunodeficiency, regular monitoring of the patient, comorbidities of the patient, and the availability of the products.
Frontiers in Immunology · 2018 · 35 citations · open access
Exome Sequencing Diagnoses X-Linked Moesin-Associated Immunodeficiency in a Primary Immunodeficiency Case
AbstractBackground We investigated the molecular aetiology of a young male proband with confirmed immunodeficiency of unknown cause, presenting with recurrent bacterial and Varicella zoster viral infections in childhood and persistent lymphopaenia into early adulthood. Aim To identify causative functional genetic variants related to an undiagnosed primary immunodeficiency. Method Whole genome microarray copy number variant (CNV) analysis was performed on the proband followed by whole exome sequencing (WES) and trio analysis of the proband and family members. A >4kbp deletion identified by repeated CNV analysis of exome sequencing data along with three damaging missense single nucleotide variants were validated by Sanger sequencing in all family members. Confirmation of the causative role of the candidate gene was performed by qPCR and Western Blot analyses on the proband, family members and a healthy control. Results CNV identified our previously reported IL25 amplification in the proband, however the variant was not validated to be a candidate gene for immunodeficiency. WES trio analysis, data filtering and in-silico prediction identified a novel, damaging (SIFT: 0; Polyphen 1; Grantham score: 101) and disease-causing (MutationTaster) single base mutation in the X chromosome (c.511C>T p.Arg171Trp) MSN gene not identified in the UCSC Genome Browser database. The mutation was validated by Sanger sequencing, confirming the proband was hemizygous X-linked recessive (-/T) at this locus and inherited the affected T allele from his non-symptomatic carrier mother (C/T), with other family members (father, sister) confirmed to be wild type (C/C). Western Blot analysis demonstrated an absence of moesin protein in lymphocytes derived from the proband, compared with normal expression in lymphocytes derived from the healthy control, father and mother. qPCR identified significantly lower MSN mRNA transcript expression in the proband compared to an age- and sex-matched healthy control subject in whole blood (P = 0.02), and lymphocytes (P = 0.01). These results confirmed moesin deficiency in the proband, directly causative of his immunodeficient phenotype. Conclusion These findings confirm X-linked moesin-associated immunodeficiency in a proband previously undiagnosed up to 24 years of age. This study also highlights the utility of WES for the diagnosis of rare or novel forms of primary immunodeficiency disease.
Oxford University Press eBooks · 2013 · 8 citations
Molecular Basis of Major Histocompatibility Complex Class II Deficiency
AbstractPrimary 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 Molecular Basis of Major Histocompatibility Complex Class II Deficiency, 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.
Postgraduate Medical Journal · 1983 · 1 citations · open access
Primary immunoglobulin deficiency and haematological disorders
AbstractNine patients with immunoglobulin deficiency and various haematological disorders are presented. In all patients, recurrent infections had antedated the onset of the haematological disorder but, in most, the possibility of primary immunodeficiency had not been considered until after the haematological diagnosis had been established. The recognition of immunodeficiency is important since such patients may require steroids, immunosuppressive therapy or splenectomy. Gammaglobulin would appear to be the appropriate therapy in this situation. Infections were reduced in all 6 patients so treated.
Personalized approach to choice-making of an immunoglobulin for the replacement therapy in patients with primary immunodeficiency - is the way to success.
AbstractImmunoglobulin replacement therapy is the most important treatment for the majority of Primary immunodeficiency (PID) forms. It is very important not only to prescribe replacement therapy, but also to choose the appropriate one according to individual patients needs at the very moment. Furthermore, in reallife clinical practice some comorbid conditions, which can occur in patient, necessitate the choice of a specific drug from a wide range of IVIG preparations presented on the Russian pharmaceutical market.
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.
