Dr Tom Gilhooly

MS Prevalence Scotland – highest rate in the world UK ~ 85,000 sufferers Rate of per 100,000 population Northern Europe

MS Is Scotland Highest prevalence in the World Genetic element Low sunlight exposure The Scottish Disease

First prescribed Aug 2004 – NHS practice Secondary progressive MS – wheelchair bound Gross tremor right hand Marked improvement on 3mg LDN LDN in MS

LDN Background Nutritional Medicine New Nutritional Medicine Clinic 2004 Omega 3 Vitamin D

Norvik Study 16 patients newly diagnosed MS AA/EPA ratio average 6 Supplement with omega 3 AA/EPA ratio reduced to % improvement in symptoms ( EDSS)

Increased incidence further from equator Low vitamin D assoc with increased autoimmunity Baseline am/pm – 2000 iu Vitamin D Baseline am/pm – 2000 iu Vitamin D Increased Th1 cells Vitamin D in MS

Above 100 nmol/l assoc 63% reduction MS Supplementing with Vit D – 40% reduction Emigration to Australia – 73% reduction Northern Australia – 73% less MS Vitamin D

LDN Trial Prescribing experience 4 years Research experience Addiction medicine 20 yrs Stats and research contacts

LDN Trial MS symptoms gradual change EDSS difficult to produce change Two patients 1mg LDN Marked improvement in bladder symptoms

LDN Trial Urinary frequency – chart MSQOL questionnaire 120 subjects Double blind RCT

LDN Trial Consultant Neurologist Dr Jonathan ORiordan MS Research Centre - Dundee Clinical Research Facility Glasgow

LDN Trial LDN Research Trust 2004 MS Society – rejection ! 2007 Chief Scientists Office Awaiting confirmation of funding

LDN Trial Mechanism of action and safety of LDN LFTs, U&Es and FBC Beta endorphins Nitrotyrosine

Medical Hypothesis 2005 Dr Agrawal

Mechanism of Action LDN

White blood cells produce two gases Nitric OxideSuperoxide Combine to produce peroxynitrite Immune Function

Medical Hypothesis – NO in pathology of MS – Louis Ignarro Giovannoni – nitric oxide metabolites in CSF MS patients Cross 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

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

ONOO in acute and chronic MS Lui – nitrotyrosine in lesions ONOO production brain cells ONOO damaging but not NO Nitric Oxide in MS

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

LDN Trial

Nitrotyrosine – nitrated amino acid Stable biomarker of ONOO activity Levels only raised in presence of ONOO Measurable in CSF Measuring ONOO

Nitrotyrosine Blood test Measure of ONOO activity New test developed in Essential Diagnostic Laboratory Glasgow First test available in world! Measuring ONOO

Tyscore Assay in Progressive MS

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%

Tyscore – Measuring Nitrotyrosine New test for MS patients Highlights increased immune activity Progressive forms of MS Key to unlock treatment

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.

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?

Crohns Disease 60 year old male patient Severe crohns – nine bloody motions daily Recent blood transfusion 19 colonoscopys Started LDN 2007

Crohns Disease Review August 2008 Normal motions for one year Complete remission of disease Single dose LDN Tyscore negative

Psoriasis Guttate Psoriasis several years Plamoplantar pustulosis 2008 Commenced LDN 1mg Sept 2008 Marked Clinical Improvement Autoimmune Disorder

Next Steps

Summary