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Novel Murine Model of Asthma Identifies Methods to Antagonize Th2 Response, Asthma and Allergic Disease

Technology Benefits
By modulating an alternative pathway (unlike current therapies), one may interfere with the immune response that tees up individuals for expressed symptoms.
Technology Application
The invention claims new therapies for bronchial asthma and other allergic diseases that may respond to regulating specific T cell responses.
Detailed Technology Description
UC inventors have developed a murine model of spontaneous asthma that closely replicates the immunologic, genetic and the clinical course of the related human disease. And, by uncovering an unknown mechanism of action, inventors have identified new means of specifically inhibiting the Th2 biased response in general, and allergic asthma in particular. This model has also enabled in vivo testing of new class of drugs that is able to block the sequence of events that culminate in human asthma.
Supplementary Information
Inventor: RAZ, Eyal | LI, Xiangli | LEE, Jihyung | INSEL, Paul A. | MURRAY, Fiona | KIM, Taehun
Priority Number: WO2014059147A1
IPC Current: A61K003935 | A61K0009127 | A61K000948 | A61K0039395 | A61P001106
Assignee Applicant: The Regents of the University of California
Title: METHODS AND COMPOSITION FOR TREATMENT OF TH2-MEDIATED AND TH17-MEDIATED DISEASES | MÉTHODES ET COMPOSITIONS POUR LE TRAITEMENT DE MALADIES À MÉDIATION PAR TH2 ET À MÉDIATION PAR TH17
Usefulness: METHODS AND COMPOSITION FOR TREATMENT OF TH2-MEDIATED AND TH17-MEDIATED DISEASES | MÉTHODES ET COMPOSITIONS POUR LE TRAITEMENT DE MALADIES À MÉDIATION PAR TH2 ET À MÉDIATION PAR TH17
Summary: The methods are used for inhibiting or activating dendritic cell induction of CD4 T cell lineage conversion to a Th2 cell; inducing CD4 T cell lineage conversion; identifying a Th2-mediated disease having symptoms similar to a Th17-mediated disease; producing a Gα s-knockout mouse; treating a Th2-mediated disease; and preventing a Th2- or Th17-mediated disease. The Th2-mediated disease comprises allergic asthma, rhinitis, conjunctivitis, dermatitis, colitis, food allergy, insect venom allergy, drug allergy or anaphylaxis-prone conditions (all claimed).
Novelty: Modulating dendritic cell induction of CD4 T cell lineage conversion to a Th2 cell comprises contacting a dendritic cell with a cyclic adenosine monophosphate-modulating agent in the presence of a CD4 T cell
Industry
Biomedical
Sub Category
Medical Composition
Application No.
2014059147
Others

State Of Development

Inventors have generated a murine model of human asthma that spontaneously reproduces the human disease. Specific, “hallmark” indicators have been assessed (serum IgE, airway hyper-reactivity, airway inflammation) to confirm the efficacy of the class of drugs claimed for their ability to abrogate the course of disease, in vivo.


Other Information

E. Raz (2013) A Novel Approach to Explore Th2-Biased Immunity: Implications for Asthma and Allergic Diseases, Manuscript in preparation (available under confidentiality)


Intellectual Property Info

Worldwide rights available; Pending patents available under confidentiality.


Related Materials

Kim HY, et al. (2010) The many paths to asthma: phenotype shaped by innate and adaptive immunity. Nat Immunol 11: 577-84
Engel MA, et al., 2010. Role of sensory neurons in colitis: increasing evidence for a neuroimmune link in the gut. Inflamm Bowel Diseases doi: 10.1002/ibd.21422
Pulendran B, et al. (2010) Programming dendritic cells to induce T(H)2 and tolerogenic responses. Nat Immunol 11: 647-55
Datta SK, et al. (2010) Mucosal adjuvant activity of cholera toxin requires Th17 cells and protects against inhalation anthrax. Proc Natl Acad Sci U S A 107: 10638-43
Barrett NA and KF Austen. 2009. Innate cells and T helper 2 cell immunity in airway inflammation. Immunity 31: 425-37
Li, X., et al. (2012) Divergent requirement for Gas and cAMP in the differentiation and inflammatory profile of distinct mouse Th subsets, J Clin Invest. Mar 1;122(3):963-73.
Lee J, et al., Cyclic AMP concentrations in dendritic cells induce and regulate Th2 immunity and allergic asthma, Proc Natl Acad Sci U S A. 2015, 3;112(5):1529-34.


Tech ID/UC Case

23253/2011-208-0


Related Cases

2011-208-0, 2013-334-0, 2014-084-0, 2013-282-0

*Abstract
Bronchial asthma is a chronic and heterogeneous inflammatory disorder of the conducting airways with immune and non-immune etiologies. Although the underlying molecular basis of asthma is not completely understood, inflammation is a key pathological feature of bronchial asthma. The increasing prevalence in Western countries (approximately 15% of children and 8% of adults) supports the vast resources deployed to find treatments and drugs that act upon pathways not targeted in current therapies are of particular interest.
*IP Issue Date
Apr 17, 2014
*Principal Investigator

Name: Xiangli Li

Department:


Name: Eyal Raz

Department:


Name: Paul Insel

Department:


Name: Jihyung Lee

Department:


Name: Fiona Murray

Department:


Name: Taehun Kim

Department:

Country/Region
USA

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