PRION DISEASE

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

• I GENERAL INTRODUCTION
• II PENTOSAN POLYSULPHATE
• III UK PATIENTS
• IV CONCLUDING POINTS

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I
GENERAL INTRODUCTION
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DIFFERENT BACKGROUNDSDIFFERENT PERSPECTIVES
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TREATMENTS HOW DO YOU EVALUATE THEM?

• IN THE TEST TUBE

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TREATMENTS HOW DO YOU EVALUATE THEM?

• IN THE TEST TUBE

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TREATMENTS HOW DO YOU EVALUATE THEM?

• PROTEINS CELLS ARE NOT ANIMALS

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TREATMENTS HOW DO YOU EVALUATE THEM?

• IN ANIMALS

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TREATMENTS HOW DO YOU EVALUATE THEM?

• RODENTS ARE NOT HUMANS

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TREATMENT AT TIME OF INFECTION IS NOT THE SAME
AS TREATING CLINICALLY ILL ANIMALS
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TREATMENTS HOW DO YOU EVALUATE THEM?

• IN THE TEST TUBE
• IN ANIMALS
• IN HUMANS

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X
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TREATMENT
REAL DISEASE BENEFIT
SYMPTOM RELIEF
TOXIC SIDE EFFECTS
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TREATMENT
REAL DISEASE BENEFIT
SYMPTOM RELIEF
TOXIC SIDE EFFECTS
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SYMPTOMS
NOT ALWAYS EASY TO TELL THE DIFFERENCE
DISEASE PROCESS
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TREATMENT
REAL DISEASE BENEFIT
SYMPTOM RELIEF
TOXIC SIDE EFFECTS
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TWO TREATMENT SITUATIONS
CLINICAL ILLNESS
PREVENTION
ANY SIDE EFFECTS MAY BE OF DIFFERENT
SIGNIFICANCE
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DISEASE
PEOPLE VARY
TREATMENT
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PERSON
SPORADIC GENETIC IATROGENIC VARIANT
DISEASES VARY
TREATMENT
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TREATMENT REQUIRES DIAGNOSIS

• THE DIAGNOSTIC PROCESS IS NOT SIMPLE
• NO SIMPLE CJD TESTS

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TREATMENT IDEALLY REQUIRES EARLY DIAGNOSIS

• STOPPING BRAIN DISEASE PREVENTS FURTHER DAMAGE
• REPAIR OF EXISTING BRAIN DAMAGE IS PROBLEMATIC
• DIAGNOSIS OF CJD IS OFTEN LATE

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TREATMENT IDEALLY REQUIRES EARLY DIAGNOSIS

• STOPPING BRAIN DISEASE PREVENTS FURTHER DAMAGE
• REPAIR OF EXISTING BRAIN DAMAGE IS PROBLEMATIC
• DIAGNOSIS OF CJD IS OFTEN LATE

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TREATMENT IDEALLY REQUIRES EARLY DIAGNOSIS

• STOPPING BRAIN DISEASE PREVENTS FURTHER DAMAGE
• REPAIR OF EXISTING BRAIN DAMAGE IS PROBLEMATIC
• DIAGNOSIS OF CJD IS OFTEN LATE

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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

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II
PENTOSAN POLYSULPHATE
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PENTOSAN POLYSULPHATE PPS
BEECH WOOD DERIVED
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PENTOSAN POLYSULPHATE PPS
BEECH WOOD DERIVED ESTABLISHED DRUG NON-PRION
DISEASE
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PENTOSAN POLYSULPHATE PPS
IN PRION DISEASE ?
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PENTOSAN POLYSULPHATE PPS
IN PRION DISEASE ?
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PENTOSAN POLYSULPHATE PPS
IN PRION DISEASE ?
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PENTOSAN POLYSULPHATE PPS
IN PRION DISEASE ?
?
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PENTOSAN POLYSULPHATE PPS
ORAL or IV DOES NOT ENTER BRAIN
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PENTOSAN POLYSULPHATE PPS
ORAL or IV DOES NOT ENTER BRAIN NEED DIRECT
ACCESS TO BRAIN
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INTRA-VENTRICULAR ADMINISTRATION
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INTRA-VENTRICULAR ADMINISTRATION
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INTRA-VENTRICULAR ADMINISTRATION
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INTRA-VENTRICULAR ADMINISTRATION
CURRENT PPS TREATMENT OF PRION DISEASE
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POTENTIAL PPS PROBLEMS
PROBLEMS WITH CATHETER SURGERY DAMAGE /
BLEEDING POST SURGERY INFECTION
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INTRA-VENTRICULAR ADMINISTRATION
PROBLEMS WITH PUMP CONNECTING TUBE
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POTENTIAL PPS PROBLEMS
PROBLEMS WITH PPS BLEEDING SEIZURES OTHER
TOXICITY
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III
PPS TREATMENT IN THE UK
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UK PPS TREATMENT

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

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ONE ORGANISED OBSERVATIONAL STUDY Published 2008
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INTRAVENTRICULAR PENTOSAN POLYSULPHATE IN HUMAN
PRION DISEASES AN OBSERVATIONAL STUDY IN THE
UKI Bone, Belton L, Walker AS, Darbyshire
JEuropean Journal of Neurology 2008, 15458-464
www.mrc.ac.uk/Utilities/Documentrecord/index.htm
?dMRC003453
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MRC STUDY PATIENTS

• 2 hGH CJD NO OBVIOUS BENEFIT
• 2 GSS NO OBVIOUS BENEFIT
• 3 vCJD 2/3 POSSIBLE BENEFIT
• (ALIVE LONGER)

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MRC STUDY PATIENTS

• 2 hGH CJD NO OBVIOUS BENEFIT
• 2 GSS NO OBVIOUS BENEFIT
• 3 vCJD 2/3 POSSIBLE BENEFIT
• (ALIVE LONGER)

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MRC STUDY PATIENTS

• 2 hGH CJD NO OBVIOUS BENEFIT
• 2 GSS NO OBVIOUS BENEFIT
• 3 vCJD 2/3 POSSIBLE BENEFIT
• (ALIVE LONGER)

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MRC STUDY PATIENTS

• 2 hGH CJD NO OBVIOUS BENEFIT
• 2 GSS NO OBVIOUS BENEFIT
• 3 vCJD 2/3 POSSIBLE BENEFIT
• (ALIVE LONGER)

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MRC STUDY PATIENTS

• 2 hGH CJD NO OBVIOUS BENEFIT
• 2 GSS NO OBVIOUS BENEFIT
• 3 vCJD 2/3 POSSIBLE BENEFIT
• (ALIVE LONGER)

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MRC STUDY PATIENTS

• SOME PROBLEMS DUE TO INTRAVENTRICULAR
  ADMINISTRATION (NO MAJOR ONES)
• NO PROBLEMS DUE TO PPS ITSELF

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MRC STUDY PATIENTS

• SOME PROBLEMS DUE TO INTRAVENTRICULAR
  ADMINISTRATION (NO MAJOR ONES)
• NO PROBLEMS DUE TO PPS ITSELF

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PRESENT UK SITUATION
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Intra-ventricular PPS Cases Treated in the UK

• Disease Treated Currently alive
• vCJD 5 4
• sCJD 1 1
• GSS 2 0
• hGH 2 0

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Intra-ventricular PPS Cases Treated in the UK

• Disease Treated Currently alive
• vCJD 5 4
• sCJD 1 1
• GSS 2 0
• hGH 2 0

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vCJD DURATION OF ILLNESS gt 20 MONTHS
September 2009
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vCJD DURATION OF ILLNESS gt 20 MONTHS
September 2009
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ALL UK vCJD DURATION OF ILLNESS
September 2009
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Intra-ventricular PPS Cases Treated in the UK

• Disease Treated Currently alive
• vCJD 5 4
• sCJD 1 1
• GSS 2 0
• hGH 2 0

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sCJD DURATION OF ILLNESS

September 2009
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IV
CONCLUDING REMARKS
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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

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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

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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

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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

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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

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• FURTHER RESEARCH ON PPS
• IF POSSIBLE RCTs

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

? EASIER ADMINISTRATION METHODS
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• TREATMENT TRIALS WITH A STRUCTURED FRAMEWORK

INTERNATIONAL COLLABORATION TRIALS WITH UNIFORM
METHODS EUROPE THERAPRION
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EARLIER TREATMENT

• EARLIER DIAGNOSIS

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EARLIER TREATMENT

• EARLIER DIAGNOSIS

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