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

2. PRION DISEASE & PPS IGENERAL INTRODUCTION IIPENTOSAN POLYSULPHATE IIIUK PATIENTS IVCONCLUDING POINTS

3. I GENERAL INTRODUCTION

4. DIFFERENT BACKGROUNDS DIFFERENT 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 BENEFITSYMPTOM RELIEFTOXIC SIDE EFFECTS

18. TREATMENT REAL DISEASE BENEFITSYMPTOM RELIEFTOXIC SIDE EFFECTS

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

20. TREATMENT REAL DISEASE BENEFITSYMPTOM RELIEFTOXIC SIDE EFFECTS

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

22. DISEASE TREATMENT PEOPLE VARY

23. PERSON SPORADIC GENETIC IATROGENIC VARIANT TREATMENT DISEASES VARY

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

41. 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 UK I Bone, Belton L, Walker AS, Darbyshire J European 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)

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

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

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

54. MRC STUDY PATIENTS SOME PROBLEMS DUE TO INTRAVENTRICULAR ADMINISTRATION (NO MAJOR ONES) NO PROBLEMS DUE TO PPS ITSELF

55. MRC STUDY PATIENTS SOME PROBLEMS DUE TO INTRAVENTRICULAR ADMINISTRATION (NO MAJOR ONES) NO PROBLEMS DUE TO PPS ITSELF

56. PRESENT UK SITUATION

57. Intra-ventricular PPS Cases Treated in the UK Disease TreatedCurrently alive vCJD54 sCJD11 GSS20 hGH20

58. Intra-ventricular PPS Cases Treated in the UK Disease TreatedCurrently alive vCJD54 sCJD11 GSS20 hGH20

59. vCJD DURATION OF ILLNESS > 20 MONTHS September 2009

60. vCJD DURATION OF ILLNESS > 20 MONTHS September 2009

61. ALL UK vCJD DURATION OF ILLNESS September 2009

62. Intra-ventricular PPS Cases Treated in the UK Disease TreatedCurrently alive vCJD54 sCJD11 GSS20 hGH20

63. sCJD DURATION OF ILLNESS September 2009 +

64. IV CONCLUDING REMARKS

65. PPS NOT A CURE HIGHLY PROBABLE: PROLONGS DISEASE IN VARIANT CJD NO GOOD EVIDENCE FOR BENEFIT IN OTHER FORMS OF CJD NO EVIDENCE OF TOXICITY FROM PPS ITSELF INTRAVENTRICULAR ADMINISTRATION IS NOT EASY

66. PPS NOT A CURE HIGHLY PROBABLE: PROLONGS LIFE IN VARIANT CJD NO GOOD EVIDENCE FOR BENEFIT IN OTHER FORMS OF CJD NO EVIDENCE OF TOXICITY FROM PPS ITSELF INTRAVENTRICULAR ADMINISTRATION IS NOT EASY

67. PPS NOT A CURE HIGHLY PROBABLE: PROLONGS LIFE IN VARIANT CJD NO PRESENT EVIDENCE FOR OTHER FORMS OF CJD NO EVIDENCE OF TOXICITY FROM PPS ITSELF INTRAVENTRICULAR ADMINISTRATION IS NOT EASY

68. PPS NOT A CURE HIGHLY PROBABLE: PROLONGS LIFE IN VARIANT CJD NO PRESENT EVIDENCE FOR OTHER FORMS OF CJD NO EVIDENCE OF TOXICITY FROM PPS ITSELF INTRAVENTRICULAR ADMINISTRATION IS NOT EASY

69. PPS NOT A CURE HIGHLY PROBABLE: PROLONGS LIFE IN VARIANT CJD NO PRESENT EVIDENCE FOR OTHER FORMS OF CJD NO EVIDENCE OF TOXICITY FROM PPS ITSELF INTRAVENTRICULAR ADMINISTRATION IS NOT EASY

70. FURTHER RESEARCH ON PPS IF POSSIBLE: RCTs ? OTHER ANIMAL RESEARCH

71. FURTHER RESEARCH ON PPS IF POSSIBLE: RCTs ? EASIER ADMINISTRATION METHODS

72. TREATMENT TRIALS WITH A STRUCTURED FRAMEWORK INTERNATIONAL COLLABORATION TRIALS WITH UNIFORM METHODS EUROPE: ‘THERAPRION’

73. EARLIER TREATMENT EARLIER DIAGNOSIS

74. EARLIER TREATMENT EARLIER DIAGNOSIS