Καθηγητής Πάνος Ε. Βάρδας MD, PhD (London, UK) Συντονιστής του Τομέα Καρδίας, Όμιλος ΥΓΕΙΑ Πρόεδρος της ESC ( ) Επισκέπτης Καθηγητής,

Transcript

1 Καθηγητής Πάνος Ε. Βάρδας MD, PhD (London, UK) Συντονιστής του Τομέα Καρδίας, Όμιλος ΥΓΕΙΑ Πρόεδρος της ESC ( ) Επισκέπτης Καθηγητής, Imperial College, UK Consultant of Zurich University Hospital Επικεφαλής Στρατηγικού Σχεδιασμού, ESC, Brussels

2 Nothing to declare related to this presentation apart the love for innovation

3

4

5 PERSPECTIVES AND POTENTIALS OF GENE THERAPY IN DEGENERATIVE CARDIOVASCULAR DISEASE THERAPEUTICS Envisaging the next years

6 THERAPEUTIC TARGETS Matrix Metalloproteinases Transforming Growth Factor Beta MicroRNAs

7 MATRIX METALLOPROTEINASES Matrix metalloproteinases (MMPs) are critical mediators of extracellular matrix (ECM) turnover. Many studies show that this enzyme family plays an important role in atherosclerotic lesion progression, vein graft failure and restenosis. There is considerable interest in MMP inhibion as a therapeutic strategy for in-stent restenosis and by pass graft failure.

8 MATRIX METALLOPROTEINASES Early studies using marimastat, a broad-spectrum MMP inhibitor, showed significantly reduced neointima formation in cultured human saphenous vein grafts. Other systemic MMP inhibitors are currently investigated in the clinic and is clear that localized therapies are needed for optimal efficacy and to limit off-target effects.

9 TRANSFORMING GROWTH FACTOR BETA The pluripotent cytokine transforming growth factor B1 (TGFB1) plays an important role in the pathological vascular remodeling that characterizes intimal hyperplasia. It has therefore been identified as a promising target for therapeutic modulation of vascular remodeling. A number of studies illustrate the potential of gene therapy-mediated antagonism of TGFB1 signaling as prophylactic therapy for in stent restenosis of bypass graft failure.

10 TRANSFORMING GROWTH FACTOR BETA Several specific TGFB inhibitors are currently being evaluated in the clinic, notably the TGB2 inhibitor Trabedersen, which is currently being evaluated in a phase III clinical trial for intratumoral delivery. These studies underline the potential importance of achieving localized, targeted inhibition of TGFb in order to obtain maximal therapeutic efficacy and minimise off-target effects.

11 MicroRNAs MicroRNAs are a class of non-coding RNAs with a short length of nucleotides. MicroRNAs (mirnas) are a novel class of non-coding RNAs, which found their way into the clinic due to their fundamental roles in cellular processes such as differentiation, proliferation and apoptosis. Recently, mirnas, have been known as micromodulators in cellular communications being involved in cell signaling and microenvironment remodeling.

12 MicroRNAs MicroRNAs due to their stability, tissue-specific expression pattern and secretion to the corresponding body fluids, are attractive targets for CV associated therapeutics. They mainly act as part translational repressors of gene expression.

13 MicroRNAs Use of anti-mir-29b oligonucleotides (cholesterol modified) after myocardial infarction, leading to upregulation of ECM proteins, leading to cardiac fibrosis (van Rooij et al., 2008). Intravenous injection of mir-92a antagomir, improved the function of damaged tissue in models of myocardial infarction (Bonauer et al., 2009). Inhibion of mir-92a results in neoangiogenic effects and functional recovery of ischemic tissues (Bonaner et al., 2009).

14 PERPECTIVES OF BIOTECHNOLOGY IN DEGENERATIVE CARDIOVASCULAR DISEASE THERAPEUTICS Envisaging the next years

15 THE NEXT TWO DECADES Miniaturatisation Transcatheter Valves New Bioabsorbable Stends Tissue Engineering Organs Bioprinting Digital Health Sensors Big Data Bedless Hospitals Artificial Intelligence

16 LEADLESS AND BATTERYLESS DEVICES

17

18

19

20

21

22

23 SUDDEN DEATH ADVANCED SOLUTIONS

24

25

26 TRANSCATHETER VALVES

27

28

29

30 MULTISENSORING

31

32

33 BEDLESS HOSPITALS

34

35 SPECIAL PUMPS AND ARTIFICIAL HEART

36

37 BIG DATA AND ANALYTICS

38

39 TISSUE ENGINEERING

40 Είναι η διαδικασία της αντικατάστασης ή αναγέννησης ανθρωπίνων κυττάρων, ιστών ή οργάνων και της αποκατάστασης της φυσιολογικής λειτουργίας του πάσχοντος οργάνου

41 Επίπεδες δομές, όπως το δέρμα, είναι οι ευκολότερες κατασκευές, αφού συνήθως αποτελούνται από ένα είδος κυττάρων Σωληνοειδείς κατασκευές, όπως τα αιμοφόρα αγγεία και η ουρήθρα, που αποτελούνται συνήθως από δύο είδη κυττάρων και χρησιμεύουν ως αγωγοί.

42 Κοίλα, μη σωληνοειδή όργανα, όπως η ουροδόχος κύστη και το στομάχι, με σύνθετη δομή και λειτουργίες. Συμπαγή όργανα, όπως οι νεφροί, η καρδία και το ήπαρ. Οπωσδήποτε, οι δομές αυτές είναι εκθετικά περισσότερο σύνθετες, καθώς αποτελούνται από πολλαπλά είδη κυττάρων.

43 Κατασκευή πάνω σε ένα πρότυπο σκελετό (scaffold) Χρήση κυττάρων από υπάρχον όργανο, μετά παλινδρόμηση σε αρχέγονες μορφές και νέα ανάπτυξη Χρήση ενός «Βιοεκτυπωτή-Bioprinter», για την κατασκευή/εκτύπωση του οργάνου στρώμα με στρώμα Ένεση κυττάρων σε ένα ζωντανό όργανο, για την επισκευή του. Χρήση χημικών/βιολογικών ουσιών για την πυροδότηση του οργάνου και αυτοεπανόρθωσή του.

44

45

46

47 Σψαφφολδ

48

49

50

51

52 HIGH QUALITY IMAGING

53

54

55

56

57

58

59

60

61

62

63

64

65

66

67

68 Thank you!!