Biomedcode modeling human disease - at a glance
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The document outlines various animal disease models utilized for studying inflammatory conditions, including rheumatoid arthritis, spondyloarthropathy, and multiple sclerosis, among others. It details specific transgenic mouse models used for evaluating the efficacy of anti-TNF therapeutics and other treatments, highlighting read-out parameters for various conditions. Additionally, the document discusses customized services for transgenic animal generation and assay development.
Biomedcode modeling human disease - at a glance
- 1. MODELING HUMAN INFLAMMATORY CONDITIONS • ACUTE INFLAMMATION • RHEUMATOID ARTHRITIS • SPONDYLOARTHROPATHY • INTESTINAL INFLAMMATION • PSORIASIS • MULTIPLE SCLEROSIS • OSTEOPOROSIS • MOLECULAR & CELLULAR ASSAYS ANIMAL DISEASE MODELS DISEASE PHENOTYPING EFFICACY EVALUATION 1
- 2. 2 Acute Inflammation Model: DGalN/LPS Hepatic failure Model LPS/Dgal in human TNF trasgenic mice (Tg1278TNFko) for the fast in vivo screenining of anti‐hTNF therapeutics. Read out parameters: Lethality, IL6 levels
- 3. 3 LPS in human TNF trasgenic mice (Tg1278TNFko) for the fast in vivo screenining of anti‐hTNF therapeutics. Read out parameters: Cytokine and chemokine profiling Cytokine Cascade Saline 0.3 1.0 3.0 TNFko Infliximab (mg/kg) Acute Inflammation Model: LPS Acute Sepsis Model Saline 0.3 1.0 3.0 TNFko Infliximab (mg/kg) Saline 0.3 1.0 3.0 TNFko Infliximab (mg/kg) Mouse GM-CSF (pg/ml)
- 4. Human TNF dependent spontaneous models of Arthritis for the preclinical efficacy evaluation of anti‐hTNF therapeutics, kinase inhibitors and others. Human TNF transgenic mice Model TNF Expression Disease Tg197 soluble & transmembrane hTNF Deregulated Arthritis Tg3647 soluble & transmembrane hTNF Deregulated Arthritis Tg5453 transmembrane hTNF Deregulated Arthritis Tg5453: transmembrane hTNF dependent fast progressing arthritis Tg197: soluble and transmembrane hTNF dependent dependent fast progressing arthritis Tg3647: soluble and transmembrane hTNF dependent slow progressing arthritis Rheumatoid Arthritis (RA) Models 4
- 5. Rheumatoid Arthritis (RA) Models Human TNF dependent spontaneous models of Arthritis for the preclinical efficacy evaluation of anti‐hTNF therapeutics, kinase inhibitors and others. Read out parameters : In vivo arthritis, weight measurements, histopathological evaluation In vivo Arthritis Histopathological Arthritis Pharmacogenomics 5
- 6. Human TNF and human TNFR1 dependent spontaneous models of Arthritis for the preclinical efficacy evaluation of anti‐hTNF and antihTNFR1 therapeutics and others Read out parameters : In vivo arthritis, weight measurement, histopathological evaluation Tg197/hTNFR1KI mice Rheumatoid Arthritis (RA) Models 6
- 7. Collagen Antibody Induced Arthritis (CAIA) CAIA induced in wild type or knock out and mutated mice for the evaluation of therapeutic targets. Read out parameters : In vivo arthritis, weight measurements, histopathological evaluation CAIA induced in C57BL6/N and C57BL6/J mice The effect of dexamethasone or Enbrel treatment in CAIA induced in C57BL6/J animals 7
- 8. Collagen Antibody Induced Arthritis (CAIA) CAIA induced in human TNF transgenic mice (Tg1278TNFko) for the preclinical efficacy evaluation of anti‐hTNF and other therapeutics targeting cytokines, kinases and other therapeutic targets. Read out parameters : In vivo arthritis, weight measurements, histopathological evaluation J Transl Med. 2014 Oct 25;12(1):285. Collagen II antibody‐induced arthritis in Tg1278TNFko mice: optimization of a novel model to assess treatments targeting human TNFa in rheumatoid arthritis. 8
- 9. Saline Etanercept Spondyloarthropathy Disease Model TNF‐DARE: A spontaneous mTNF‐dependent dual disease mouse model of spondyloarthropathy and intestinal inflammation for the preclinical efficacy evaluation of anti‐TNF and other therapeutics in two pathologies simultaneously Read out parameters: In vivo arthritis (grip strength), weight measurements, arthritis and ileitis histopathological evaluation 9
- 10. Intestinal Bowel Disease Model TNBS colitis in human TNF transgenic mice for the preclinical efficacy evaluation of anti‐hTNF therapeutics Read out parameters: weight measurements, histopathological evaluation, thick organ cultures and cytokine detection Adalimumab Saline 10
- 11. A human RANKL transgenic mouse model (Tg5519) of spontaneous osteoporosis for the evaluation of anti‐hRANKL and other therapeutics. Read out parameters: weight measurements, histopathological evaluation, microCT, biochemical monitoring of bone metabolism WT Saline Denosumab H&E TRAP Osteoporosis Model 11
- 12. Psoriasis Model Imiquimod (IMQ) induced psoriasis in wild type and human IL17a transgenic mice for the preclinical efficacy evaluation of anti‐hIL17 and other therapeutics. Read out parameters: Skin erythema, skin thickening and scaling, weight measurements, histopathological evaluation. IMQ psoriatic skin Normal skin 12
- 13. Multiple Sclerosis Model MOG35‐55‐induced Experimental Autoimmune Encephalomyelitis (EAE) in wild type or humanized mouse models for the preclinical efficacy evaluation of anti‐hTNFR1 and other therapeutics. Read out parameters : weight measurements, in vivo clinical scoring, histopathological evaluation. Wild type animals hTNFR1KI animals 13
- 14. Ex vivo and In vitro Assays •Histopathology •Whole organ cutlure •Cytokine analysis •Molecular Assays •Cellular Assays •Pharmacogenomics analysis 14
- 15. Customized Services •Generation of transgenic, knock out and humanized animals •Phenotyping of knock out mice in a disease context •Novel mouse model development •Novel assay development •Pharmacokinetics/Pharmacodynamics •Customized specimen collection •Immunohistochemisry •Pharmacogenomics 15
- 16. Biomedcode at a glance 16