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Immune Monitoring & Targeted Therapeutics Innovative Programs to Advance Health Research (LSDF 07-02) Program for Autoimmune Disease Intervention (PADI)

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Presentation on theme: "Immune Monitoring & Targeted Therapeutics Innovative Programs to Advance Health Research (LSDF 07-02) Program for Autoimmune Disease Intervention (PADI)"— Presentation transcript:

1 Immune Monitoring & Targeted Therapeutics Innovative Programs to Advance Health Research (LSDF 07-02) Program for Autoimmune Disease Intervention (PADI) Interdisciplinary translational research applied to autoimmune diseases to improve health outcomes

2 Unmet medical need Scientific opportunities Economic growth opportunities Program for Autoimmune Disease Intervention

3 Autoimmune Diabetes Multiple sclerosis Lupus Alopecia areata Ankylosing spondylitis Addisons disease Hemolytic anemia Autoimmune Hepatitis Thrombocytopenic purpura Behcets disease Pemphigus Crohns disease Dermatomyositis Graves disease Hashimotos Thyroiditis Myasthenia gravis Pernicious anemia Polyarteritis Polychondritis Polymyositis Psoriasis Rheumatoid arthritis Scleroderma Sjogren’s syndroms Stiff man syndrome Giant cell Arteritis Ulcerative colitis Vasculitis Uveitis Vitiligo Autoimmune Diseases

4 Unmet medical need Program for Autoimmune Disease Intervention Autoimmune diseases affect 50 million in the US, and are one of the top 10 leading causes of death in children and women age 65 and younger.

5 Unmet medical need Program for Autoimmune Disease Intervention Morbidity and mortality are directly related to late diagnosis, lack of effective treatments, and problems in access to care;

6 Scientific Opportunity Program for Autoimmune Disease Intervention Morbidity and mortality are directly related to late diagnosis, lack of effective treatments, and problems in access to care;

7 Scientific Opportunity: We now, for the first time, can identify, isolate, and study the cells (specific lymphocytes) which trigger and cause autoimmune diseases Program for Autoimmune Disease Intervention

8 ”Enabling Technology”: co-opt molecular mechanisms responsible for immune specificity Immune lymphocyte Antigen presenting cell

9 Precise molecular handshakes provide the cell-to-cell contacts responsible for immune specificity Immune lymphocyte Antigen presenting cell

10 Precise molecular handshakes provide the cell-to-cell contacts responsible for immune specificity Immune lymphocyte Antigen presenting cell

11 Mimic the body’s molecular strategy Immune lymphocyte Antigen presenting cell

12 HLA Tetramer =

13

14 Early treatment is the goal; Early identification of autoimmunity is the key Genetic Predisposition Surviving islet cells Immune activation Normal insulin release Progressive loss of islet cells Glucose normal Overt diabetes Time 

15 TMr-GAD + CD4 +

16 The therapeutic window for intervention using immunomodulation Genetic Predisposition Surviving islet cells Immune activation Normal insulin release Progressive loss of islet cells Glucose normal Overt diabetes Time 

17 The therapeutic window for intervention using immunomodulation Genetic Predisposition Surviving islet cells Immune activation Normal insulin release Glucose normal Time  Immune regulation

18 The Pipeline of Immunotherapy Trials in New Onset Type 1 Diabetes MMF and DZB HSP 65 p277 Multi-dose DZB Exanitide and DZB Multidose anti-CD3 Anti-CD20 CTLA4-Ig Rapamycin and IL-2 Phase III Anti-CD3 Anti-CD3 and Exanitide GAD 65 in Alum Proinsulin DNA Vaccine ATG Anti-CD3 and insulin

19 type 1 diabetes and multiple sclerosis and lupus? Related by: genetic susceptibility, molecular mechanisms, potential therapeutics directed at fundamental immune pathways; Program for Autoimmune Disease Intervention

20 TGEM: Tetramer Guided Epitope Mapping 0.2% 23.2% 5.2% 71.4% 0.0% 21.1% 0.1% 78.8% 0.1% 19.4% 11.2% 69.3% 0.0% 17.9% 0.0% 82.0% 0.0% 17.4% 0.1% 82.5% Overlapping peptides Pooled peptides Pooled tetramers FACS staining with pooled tetramer of VP16- stimulated PBMC Tetramers loaded with single peptide FACS staining with peptide-specific tetramer Patient blood sample for analysis

21 Program for Autoimmune Disease Intervention Our vision for this Program is to evaluate new and emerging markers of lymphocyte lineage and function, in combination with new and emerging markers of genetic propensity for autoimmune phenotypes, in patients at all stages of autoimmune disease—from predisposition through disease diagnosis and response to immunotherapy.

22 Health Impact “Deliverables”: A toolkit for a new approach to autoimmunity

23 Program for Autoimmune Disease Intervention We anticipate that a successful result from this Program will be the widespread use of such profiling tools for early diagnosis, selection of therapy, monitoring of therapy, and design of the next generation clinical trials for T1D, MS, and lupus. …better outcomes …reduced costs

24 Scientific Opportunity Program for Autoimmune Disease Intervention Morbidity and mortality are directly related to late diagnosis, lack of effective treatments, and problems in access to care;

25 Mimic the body’s molecular strategy Immune lymphocyte Antigen presenting cell

26 Autoantigen targeting – the PADI interdisciplinary approach to novel autoimmune therapy Program for Autoimmune Disease Intervention

27 Immediate benefits Program for Autoimmune Disease Intervention Morbidity and mortality are directly related to late diagnosis, lack of effective treatments, and problems in access to care;

28 Greater Seattle Tacoma Olympia Vancouver Wenatchee Spokane Bellingham Everett Yakima Tri-Cities Program for Autoimmune Disease Intervention State-wide network of collaborating providers Access to trials, Education of patients and families

29 Key LSDF elements –Institutional Commitment –Partnerships with other organizations –Financial cost-sharing –Deliverables –Milestones –Commercialization plan Program for Autoimmune Disease Intervention

30 Economic track record Jeffrey Ledbetter Martha Hayden- Ledbetter Edward Clark Inventors of abatacept (CTLA4Ig) Chimeric CD20 Mabs Founders of Trubion Pharmaceuticals Program for Autoimmune Disease Intervention

31 Jane BucknerTranslational Medicine Carla GreenbaumClinical Trials Heather ShillingGenotyping Core Keith Elkon (UW)Lupus targeting Mark Wener (UW)Lupus clinic Mariko KitaMultiple Sclerosis Jerry NepomImmunomonitoring Program for Autoimmune Disease Intervention

32 Translational Immunology Registry-repository-autoimmunity-allergy-asthma-matrix biology Clinical Trials NIDDK TrialNet, NIAID ITN, JDRF, SWOG, IIT (VM) 215 employees 20 senior scientists $26 million/year research volume 65% from competitive research grants the rest from pharma/biotech, donations, endowment Formerly the Virginia Mason Research Center, est 1956


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