DeCure for Combined immunodeficiency due to MALT1 deficiency
DeCure's autonomous Immuno AI scientist is researching a drug-repurposing hypothesis for combined immunodeficiency due to MALT1 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 MALT1 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 malt1 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
MALT1 paracaspase (MALT1) — MALT1 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 1~{s}drag to rotate · scroll to zoom
RCSB Protein Data Bank · entry 7A41 · 2.13 Å · ligand ~{N}-[(1~{S})-1-[4-[[2-chloranyl-7-[(1~{S})-1-methoxyethyl]pyrazolo[1,5-a]pyrimidin-6-yl]amino]phenyl]-2,2,2-tris(fluoranyl)ethyl]-~{N}-methyl-1,1-bis(oxidanylidene)thiane-4-carboxamide (QYQ). Experimental structure, not a prediction.
What the evidence adds up to
A 2020 case report identified a homozygous MALT1 mutation (c.1454 A>G, p.Asn485Ser) in an infant who died from severe combined immunodeficiency. The mutation was associated with absence of T cell activation and production of immature lymphocytes. No other MALT1 mutations in SCID patients are described in these abstracts, and no treatment was attempted in that case.
A 2018 in vitro study knocked down MALT1 in CD3+ T cells from patients with various haematological malignancies and observed suppression of T cell activation and proliferation. Microarray analysis showed altered expression of ZAP-70, p65, MDM2, ATM, and NFATC2, implicating NF-κB, p53, and NFAT pathways. The authors concluded that MALT1 suppression may contribute to T cell immunodeficiency, but the work was done in cancer patients, not in individuals with germline MALT1 deficiency.
Two review articles (2017, 2019) discuss primary immunodeficiencies generally. They note that SCID is life-threatening, that X-linked SCID accounts for roughly 46% of cases in the United States, and that diagnosis remains poor in less affluent countries. Neither review mentions MALT1 deficiency specifically or any drug that targets it.
No clinical trial, no repurposed drug, and no survival or response rate data for MALT1 deficiency appear in these abstracts. What is missing is any patient cohort large enough to test a drug, any funding for such a trial, and any molecular stratification that might distinguish MALT1-deficient SCID from other forms.
Evidence
Retrieved by DeepSearch across 234,678,978 indexed works and resolved on OpenAlex — ranked by citations, including the results that did not work.
Frontiers in Immunology · 2017 · 45 citations · open access
Primary Immunodeficiency Disorders in India—A Situational Review
AbstractPrimary immunodeficiency disorders (PIDs) are a group of genetic defects characterized by abnormalities of one or more components of the immune system. While there have been several advances in diagnosis, management, and research in the field of PIDs, they continue to remain underdiagnosed, especially in the less affluent countries. Despite several limitations and challenges, India has advanced significantly in the field of PIDs in the last few years. In this review, we highlight the progress in the field of PIDs in India over the last 25 years, the difficulties faced by clinicians across the country, the current state of PIDs in India and the future prospects.
Immunology and Genetics Journal · 2020 · 5 citations
Case Report: MALT1 Mutation in A Patient with Severe Combined Immunodeficiency
AbstractSevere combined immunodeficiency (SCID) is one of the most serious and life-threatening forms of primary immunodeficiency disorders (PID). SCID patients manifest a large clinically heterogeneous group of monogenic disorders caused by a defect in human innate and adaptive immune response. It leads to an increased susceptibility to variety of infections, sometimes with fetal outcome. To date, more than 30 candidate genes and mutations in patients with SCID phenotype have been identified. We found a homozygous variation (c.1454 A>G_ p. Asn485Ser) in the MALT1 identified by WES in an expired infant with SCID. The mutation in MALT1 is associated with absence of T cell activation, which produces immature lymphocytes leading to SCID.
AbstractThis chapter provides a brief overview of major primary and acquired immunodeficiency disorders of the human immune system. It aims to assimilate information regarding immunodeficiency diseases, their current classification, causes and treatment options. Immunodeficiency diseases are a major cause of mortality and morbidity. These diseases result from the malfunction of the immune system and this malfunction can stem from many causes. The International Union of Immunological Societies Expert Committee on Primary Immunodeficiency has reviewed the classification of Primary immunodeficiency diseases every 2 years since its inception in 1973. Human severe combined immunodeficiency (SCID) was first reported by Swiss workers more than 50 years ago. X-linked recessive severe combined immunodeficiency is the most common form of SCID and accounts for roughly 46% of the cases in the United States. Common variable immune deficiency as a heterogeneous group of primary immune deficiencies is characterized by insufficient serum levels of immunoglobulins, reduced response to specific antigens and higher incidence of repeated infections.
ImmunoTargets and Therapy · 2018 · 1 citations · open access
Alteration of gene expression profile in CD3<sup>+</sup> T-cells after downregulating MALT1
AbstractBackground: T cell immunodeficiency is a common feature in patients with different kinds of hematological disease such as T cell non-Hodgkin lymphoma (T-NHL), B cells NHL (B-NHL), NK/T cell NHL (NK/T-CL) and acute myeloid leukemia (AML). In our recent research, we found that significantly lower expression levels in MALT1 and NF-κB were related to suppression of T cell activation. Therefore, this study was conducted to further investigate the role of downregulating MALT1 in the development of immunodeficiency in T cells. Methods: We induced activation inhibition in CD3 + T cells by MALT1 knockdown. Then we characterized the gene expression profile after MALT1 suppression by microarray analysis. Result: The differentially expressed genes were ZAP-70 , p65 , MDM2 , ATM , NFATC2 which participate in the NF-κB, p53, and NFAT pathways in CD3 + T cells after MALT1 downregulation. Conclusion: MALT1 suppression may contribute to immunodeficiency in T cells via suppression of T cell activation and proliferation pathways. These data may help to explain some of the characteristics of immunodeficiency of T cells. Keywords: CD3 + T-cells, MALT1, immunodeficiency, T-cell activation, microarray
Oxford University Press eBooks · 2013 · 0 citations
Deficiency of FOXN1
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 Deficiency of FOXN1, 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.
