PRION DISEASE & PENTOSAN POLYSULPHATE IN THE UK

1. PRION DISEASE & PENTOSAN POLYSULPHATE IN THE UK Richard Knight NCJDSU University of Edinburgh Scotland

2. PRION DISEASE & PPS I GENERAL INTRODUCTION II PENTOSAN POLYSULPHATE III UK PATIENTS IV CONCLUDING POINTS

3. I GENERAL INTRODUCTION

4. DIFFERENT BACKGROUNDSDIFFERENT PERSPECTIVES

5. TREATMENTS: HOW DO YOU EVALUATE THEM? • IN THE ‘TEST TUBE’

6. TREATMENTS: HOW DO YOU EVALUATE THEM? • IN THE ‘TEST TUBE’

7. TREATMENTS: HOW DO YOU EVALUATE THEM? PROTEINS & CELLS ARE NOT ANIMALS

8. TREATMENTS: HOW DO YOU EVALUATE THEM? • IN ANIMALS

9. TREATMENTS: HOW DO YOU EVALUATE THEM? RODENTS ARE NOT HUMANS

13. TREATMENT AT TIME OF INFECTION IS NOT THE SAME AS TREATING CLINICALLY ILL ANIMALS

15. TREATMENTS: HOW DO YOU EVALUATE THEM? • IN THE ‘TEST TUBE’ • IN ANIMALS • IN HUMANS

16. X

17. TREATMENT REAL DISEASE BENEFIT SYMPTOM RELIEF TOXIC SIDE EFFECTS

18. TREATMENT REAL DISEASE BENEFIT SYMPTOM RELIEF TOXIC SIDE EFFECTS

19. SYMPTOMS NOT ALWAYS EASY TO TELL THE DIFFERENCE DISEASE PROCESS

20. TREATMENT REAL DISEASE BENEFIT SYMPTOM RELIEF TOXIC SIDE EFFECTS

21. TWO TREATMENT SITUATIONS CLINICAL ILLNESS PREVENTION ANY SIDE EFFECTS MAY BE OF DIFFERENT SIGNIFICANCE

22. DISEASE PEOPLE VARY TREATMENT

23. PERSON SPORADIC GENETIC IATROGENIC VARIANT DISEASES VARY TREATMENT

24. TREATMENT REQUIRES DIAGNOSIS THE DIAGNOSTIC PROCESS IS NOT SIMPLE NO SIMPLE ‘CJD TESTS’

25. TREATMENT IDEALLY REQUIRES EARLY DIAGNOSIS STOPPING BRAIN DISEASE PREVENTS FURTHER DAMAGE REPAIR OF EXISTING BRAIN DAMAGE IS PROBLEMATIC DIAGNOSIS OF CJD IS OFTEN ‘LATE’

26. TREATMENT IDEALLY REQUIRES EARLY DIAGNOSIS STOPPING BRAIN DISEASE PREVENTS FURTHER DAMAGE REPAIR OF EXISTING BRAIN DAMAGE IS PROBLEMATIC DIAGNOSIS OF CJD IS OFTEN ‘LATE’

27. TREATMENT IDEALLY REQUIRES EARLY DIAGNOSIS STOPPING BRAIN DISEASE PREVENTS FURTHER DAMAGE REPAIR OF EXISTING BRAIN DAMAGE IS PROBLEMATIC DIAGNOSIS OF CJD IS OFTEN ‘LATE’

28. TREATMENT IDEALLY REQUIRES EARLY DIAGNOSIS STOPPING BRAIN DISEASE PREVENTS FURTHER DAMAGE REPAIR OF EXISTING BRAIN DAMAGE IS PROBLEMATIC DIAGNOSIS OF CJD IS OFTEN ‘LATE’ MAY BE SEVERE, IRREVERSIBLE, DAMAGE

29. II PENTOSAN POLYSULPHATE

30. PENTOSAN POLYSULPHATE: PPS BEECH WOOD DERIVED

31. PENTOSAN POLYSULPHATE: PPS BEECH WOOD DERIVED ESTABLISHED DRUG NON-PRION DISEASE

32. PENTOSAN POLYSULPHATE: PPS IN PRION DISEASE ?

33. PENTOSAN POLYSULPHATE: PPS IN PRION DISEASE ?

34. PENTOSAN POLYSULPHATE: PPS IN PRION DISEASE ?

35. PENTOSAN POLYSULPHATE: PPS IN PRION DISEASE ? ?

36. PENTOSAN POLYSULPHATE: PPS ORAL or IV: DOES NOT ENTER BRAIN

37. PENTOSAN POLYSULPHATE: PPS ORAL or IV: DOES NOT ENTER BRAIN NEED DIRECT ACCESS TO BRAIN

38. INTRA-VENTRICULAR ADMINISTRATION

39. INTRA-VENTRICULAR ADMINISTRATION

40. INTRA-VENTRICULAR ADMINISTRATION

41. INTRA-VENTRICULAR ADMINISTRATION CURRENT PPS TREATMENT OF PRION DISEASE

42. POTENTIAL PPS PROBLEMS PROBLEMS WITH CATHETER SURGERY: DAMAGE / BLEEDING POST SURGERY: INFECTION

43. INTRA-VENTRICULAR ADMINISTRATION PROBLEMS WITH PUMP & CONNECTING TUBE

44. POTENTIAL PPS PROBLEMS PROBLEMS WITH PPS BLEEDING SEIZURES OTHER TOXICITY

45. III PPS TREATMENT IN THE UK

46. UK PPS TREATMENT • NO ORGANISED CLINICAL TRIAL • COLLECTION OF INFORMATION ON A FEW INDIVIDUALS WHO CHOSE TREATMENT or WHOSE FAMILIES CHOSE TREATMENT

47. ONE ORGANISED OBSERVATIONAL STUDY Published 2008

48. INTRAVENTRICULAR PENTOSAN POLYSULPHATE IN HUMAN PRION DISEASES: AN OBSERVATIONAL STUDY IN THE UKI Bone, Belton L, Walker AS, Darbyshire JEuropean Journal of Neurology 2008, 15:458-464 www.mrc.ac.uk/Utilities/Documentrecord/index.htm?d=MRC003453

49. MRC STUDY PATIENTS • 2 hGH CJD NO OBVIOUS BENEFIT • 2 GSS NO OBVIOUS BENEFIT • 3 vCJD 2/3 POSSIBLE BENEFIT (ALIVE LONGER)

50. MRC STUDY PATIENTS • 2 hGH CJD NO OBVIOUS BENEFIT • 2 GSS NO OBVIOUS BENEFIT • 3 vCJD 2/3 POSSIBLE BENEFIT (ALIVE LONGER)