Neue Technologien für die patientennahe personalisierte Diagnostik

Transcription

1 Neue Technologien für die patientennahe personalisierte Diagnostik 2014 Dr. Soeren Schumacher, M.B.A. 27th of June

2 A heterogeneous pool 27th of June

3 A heterogeneous pool Personalized Medicine is a unique approach to medical practice in which the individual aspects of a patient are directly considered to guide treatment planning, including his or her genetic make-up, key biomarkers, prior treatment history, environmental factors and behavioural preferences. This approach can be used to optimize pharmaceutical treatments and overall care. (Source: Pfizer Homepage) 27th of June

4 Biomarker 27th of June

5 Biomarker 27th of June

6 Biomarker Where does it go? 27th of June

7 Biomarker Beyond 2020 Understanding the Structure of the Genome Understanding the Biology of Genomes Understanding the Biology of Diseases Advancing the Science of Medicine Improving the Effectiveness of Healthcare adapted from McLeod, th of June

8 Biomarker FOCUSED PROTEOMICS Traditional Biochemistry Candidates Empiric Biomarker Research adapted from MacBeath, Nature, th of June

9 Just to give an example... Seven Biomarkers Glucose Ferritin HbA1c IL-2 receptor alpha Insuline Adiponectin hs-crp 27th of June

10 Diagnostic value chain Riskscreening Presymptomatic diagnostic Early detection Acute diagnosis Companion Diagnostics Therapy control In future: more reasons and occasions for diagnosis increasing demand 27th of June

11 Pharma/Diagnostic Co-Development 27th of June

12 Development pipelines Target selection Target validation Basic Research Target selection Target validation Prototype assay Assay validation Analytical validation Plausability of stratification Clinical Validation Clinical Validation of stratification process Preclinical and non-clinical development Clinical development Approval, Launch Non-clinical efficacy Toxicity Pharmacology Phase 1 Phase 2 Phase 3 Marketing 27th of June

13 Creation of value Value chain of in-vitro diagnostics Taking of a sample Transfer to laboratory Analysis of sample Transmission of results Therapeutic action Step 1 Step 2 Step 3 Step 4 Step 5 27th of June

14 Creation of value Value chain of in-vitro diagnostics Impact of new biomarker? Taking of a sample Transfer to laboratory Analysis of sample Transmission of results Therapeutic action Step 1 Step 2 Step 3 Step 4 Step 5 27th of June

15 Creation of value Value chain of in-vitro diagnostics Impact of point-of-care diagnostics? Taking of a sample Transfer to laboratory Analysis of sample Transmission of results Therapeutic action Step 1 Step 2 Step 3 Step 4 Step 5 27th of June

16 Added value of point-of-care testing 27th of June

17 Market growth (CAGR) Application areas - BCG-matrix Stars Question marks 5 1. Infectious diseases Self-monitoring blood glucose 3. Cardiac markers 4. Blood gases and electrolytes 5. Coagulation Cash cows Poor dogs Revenues 27th of June

18 Lessons learned Diagnostic has to be more frequently available move back to the patient be miniaturized for patient-friendly use be more versatile (more parameters) 27th of June

19 Lessons learned Patient-near diagnostic 27th of June

20 Platform technology for near-patient testing 27th of June

21 Core element: Self-contained cartridge 27th of June

22 Core element: Self-contained cartridge Schumacher S., et al Lab Chip 12, th of June

23 Base-unit: 14 x 14 x 14 cm 27th of June

24 Open-platform Antigen assay Serological assay DNA assay = Antibody (labelled) = Antibody CCD CAMERA = Antigen Brandenburg A, et al Sens Act B 139, th of June

25 Inflammation monitoring Acute phase protein Immunological assay Immobilized antibodies Fluorescently labelled detection antibody Concentration ranges µg/ml CRP 27th of June

26 Inflammation monitoring 27th of June

27 Inflammation monitoring 27th of June

28 Inflammation monitoring 27th of June

29 Inflammation monitoring External calibration Concordance - 22 patient samples 27th of June

30 Antibiotic resistances Evaluation of antibiotic resistance genes Application: Assay type: Reagents: Assay time: Performance: Comment: SNP-detection DNA hybridization Capture molecule - DNA-probes ~ 10 minutes Successful discrimination of variants Hybridization experiments after external PCR, different variants could be differentiated 27th of June

31 Antibiotic resistances 27th of June

32 Antibiotic resistances Essential structure of all quinolone antibiotics Nalidixic acid Ciprofloxacin 1st generation 2nd generation Levofloxacin 3rd generation Trovafloxacin 4th generation Structure of bacterial DNA gyrase complexed with DNA and two ciprofloxacin molecules (green) 27th of June

33 Antibiotic resistances In Gram-negative bacteria, plasmidmediated resistance genes produce proteins that can bind to DNA gyrase, protecting it from the action of quinolones. Cyprofloxacin, most prescribed antibiotic against UTIs from gram negative bacteria (e.g. E. coli). Antibiotic Misuse: 99% of these prescriptions were revealed to be in error. Quinolone Resistance: responsible are point mutations (SNPs) in several genes: gyra, gyrb, parc, pare 27th of June

34 Antibiotic resistances SNP: gyra gene SNP position WT C G A Isolate 5 T A A Isolate 12 C G G Isolate 16 T T A 25 probes 27th of June

35 Antibiotic resistances hybridised with DNA from isolate 12 C G G CGG = correct identification of isolate 12 27th of June

36 Antibiotic resistances A COP slides B ivd-platform 27th of June

37 Antibiotic resistances 27th of June

38 Your assay at the point-of-care 27th of June

39 Fraunhofer ivd-partnering Three steps 1. Transfer of the assay into the Fraunhofer ivd-platform 2. Validation of biomarker in clinical trials within the system (MPG; ivd) 3. Usage of easy-scaleable materials enables a low-cost production 27th of June

40 Summary Personalized Medicine will bring added value to patients as well as health care systems Personalized Diagnostics will be multiparametric Diagnostics in general needs to be more frequently available Point-of-Care Diagnostics will give An added-value due to fast medical decision making 27th of June

41 ACKNOWLEDGEMENT Consortium Fraunhofer ivd-platform Assay development team Nikitas Bistolas Edda Reiß Harald Peter Sabrina Schulz Base-unit development team Jörg Henkel Peter Kozma André Lehmann Ralph Hölzel University of Edinburgh Till Bachmann Holger Schulz Get in contact: th of June