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

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

I GENERAL INTRODUCTION

DIFFERENT BACKGROUNDS DIFFERENT PERSPECTIVES

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

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

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

TREATMENTS: HOW DO YOU EVALUATE THEM? IN ANIMALS

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

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

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

X

TREATMENT REAL DISEASE BENEFITSYMPTOM RELIEFTOXIC SIDE EFFECTS

TREATMENT REAL DISEASE BENEFITSYMPTOM RELIEFTOXIC SIDE EFFECTS

DISEASE PROCESS SYMPTOMS NOT ALWAYS EASY TO TELL THE DIFFERENCE

TREATMENT REAL DISEASE BENEFITSYMPTOM RELIEFTOXIC SIDE EFFECTS

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

DISEASE TREATMENT PEOPLE VARY

PERSON SPORADIC GENETIC IATROGENIC VARIANT TREATMENT DISEASES VARY

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

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

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

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

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

II PENTOSAN POLYSULPHATE

PENTOSAN POLYSULPHATE: PPS BEECH WOOD DERIVED

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

PENTOSAN POLYSULPHATE: PPS IN PRION DISEASE ?

PENTOSAN POLYSULPHATE: PPS IN PRION DISEASE ?

PENTOSAN POLYSULPHATE: PPS IN PRION DISEASE ?

PENTOSAN POLYSULPHATE: PPS IN PRION DISEASE ? ?

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

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

INTRA-VENTRICULAR ADMINISTRATION

CURRENT PPS TREATMENT OF PRION DISEASE

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

INTRA-VENTRICULAR ADMINISTRATION PROBLEMS WITH PUMP & CONNECTING TUBE

POTENTIAL PPS PROBLEMS PROBLEMS WITH PPS BLEEDING SEIZURES OTHER TOXICITY

III PPS TREATMENT IN THE UK

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

ONE ORGANISED OBSERVATIONAL STUDY Published 2008

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:

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

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

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

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

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

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

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

PRESENT UK SITUATION

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

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

vCJD DURATION OF ILLNESS > 20 MONTHS September 2009

vCJD DURATION OF ILLNESS > 20 MONTHS September 2009

ALL UK vCJD DURATION OF ILLNESS September 2009

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

sCJD DURATION OF ILLNESS September

IV CONCLUDING REMARKS

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

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

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

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

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

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

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

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

EARLIER TREATMENT EARLIER DIAGNOSIS

EARLIER TREATMENT EARLIER DIAGNOSIS