LDN Prescribing And Research In Scotland
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Transcript of LDN Prescribing And Research In Scotland
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Dr Tom GilhoolyDr Tom Gilhooly
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MS Prevalence
Scotland – highest rate in the world
UK ~ 85,000 sufferers
Rate of 143.8 per 100,000 population
Northern Europe
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MS Is Scotland
Highest prevalence in the World
Genetic element
Low sunlight exposure
“The Scottish Disease”
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First prescribed Aug 2004 – NHS practice
Secondary progressive MS – wheelchair bound
Gross tremor right hand
Marked improvement on 3mg LDN
LDN in MS
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LDN
Background Nutritional Medicine
New Nutritional Medicine Clinic 2004
Omega 3
Vitamin D
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Norvik Study
16 patients newly diagnosed MS
AA/EPA ratio average 6
Supplement with omega 3
AA/EPA ratio reduced to 1.5
25% improvement in symptoms ( EDSS)
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Increased incidence further
from equator
Increased incidence further
from equator
Low vitamin D assoc with increased
autoimmunity
Low vitamin D assoc with increased
autoimmunity
Baseline am/pm – 2000 iu Vitamin D
Baseline am/pm – 2000 iu Vitamin D
Increased Th1 cells
Increased Th1 cells
Vitamin D in MS
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Above 100 nmol/l assoc 63%
reduction MS
Above 100 nmol/l assoc 63%
reduction MS
Supplementing with Vit D – 40%
reduction
Supplementing with Vit D – 40%
reduction
Emigration to Australia – 73%
reduction
Emigration to Australia – 73%
reduction
Northern Australia – 73%
less MS
Northern Australia – 73%
less MS
Vitamin D
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LDN Trial
Prescribing experience 4 years
Research experience
Addiction medicine 20 yrs
Stats and research contacts
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LDN Trial
MS symptoms gradual change
EDSS difficult to produce change
Two patients 1mg LDN
Marked improvement in bladder symptoms
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LDN Trial
Urinary frequency – chart
MSQOL questionnaire
120 subjects
Double blind RCT
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LDN Trial
Consultant Neurologist
Dr Jonathan O’Riordan
MS Research Centre - Dundee
Clinical Research Facility Glasgow
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LDN Trial
LDN Research Trust 2004
MS Society – rejection ! 2007
Chief Scientists Office - 2008
Awaiting confirmation of funding
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LDN Trial
Mechanism of action and safety of LDN
LFTs, U&Es and FBC
Beta endorphins
Nitrotyrosine
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Medical Hypothesis 2005
Dr Agrawal
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Mechanism of Action LDN
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Mechanism of Action LDN
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White blood cells produce two gases
Nitric Oxide Superoxide
Combine to produce peroxynitrite
Immune Function
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Medical Hypothesis – NO in pathology of MS – Louis
Ignarro
Giovannoni – nitric oxide metabolites in CSF MS patientsCross et al – nitrotyrosine in MS
lesions
Nobel Prize NO in Heart Disease Louis Ignarro
Nitric Oxide in MS
Animal studies showed ONOO damaged nerve cells
and produced MS type lesions
1988
2001
1998
1992
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Danilov – nitric oxide products in
progressive and RRMS
Increased amounts during relapse
Redjak et al
Calabrese – iNOS in MS patients CSF
Nitrotyrosine in CSF
Nitric Oxide in MS
2002 2004
2003
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ONOO in acute and chronic MS
Lui – nitrotyrosine in lesions
ONOO production brain cells
ONOO damaging but not NO
Nitric Oxide in MS
2006 2008
2007
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Rejdak et al Neurology 2004
Examined NO metabolites in CSF
Correlates to MRI scan lesions
Greater levels in those with less disability
Correlation NO levels and severity of disability/MRI appearance at 3 yrs
2008 – nitrosative stress assoc with sustained disability in MS
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LDN Trial
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Nitrotyrosine – nitrated amino acid
Stable biomarker of ONOO activity
Levels only raised in presence of ONOO
Measurable in CSF
Measuring ONOO
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Nitrotyrosine Blood test
Measure of ONOO activity
New test developed in Essential Diagnostic Laboratory Glasgow
First test available in world!
Measuring ONOO
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Tyscore Assay in Progressive MS
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Tyscore
Measuring disease activity
Increased Tyscore in absence of clinical signs
25% of progressive MS patients have raised levels
Treatment with steroids/co paxone/LDN may reduce levels and disability
25%
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Tyscore – Measuring Nitrotyrosine
New test for MS patients
Highlights increased immune activity
Progressive forms of MS
Key to unlock treatment
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New Paradym In MS Treatment
75% of all MS patients have progressive disease
Majority are not in active treatment
Tyscore can help identify the periods of increased immune activity.
Active treatment at these times has potential to reduce/prevent disability.
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Does LDN work soley through endorphin increase ?
Does LDN/other Rx reduce the Tyscore?
How do we respond to a raised Tyscore?
Cost implications of treating more MS ?
Unanswered Questions?
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Crohn’s Disease
60 year old male patient
Severe crohn’s – nine bloody motions daily
Recent blood transfusion
19 colonoscopys
Started LDN 2007
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Crohn’s Disease
Review August 2008
Normal motions for one year
Complete remission of disease
Single dose LDN
Tyscore negative
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Psoriasis
Guttate Psoriasis several years
Plamoplantar pustulosis 2008
Commenced LDN 1mg Sept 2008
Marked Clinical Improvement
Autoimmune Disorder
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Next Steps
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Summary