Dr Tom GilhoolyDr Tom Gilhooly

MS Prevalence

Scotland – highest rate in the world

UK ~ 85,000 sufferers

Rate of 143.8 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 1.5

25% improvement in symptoms ( EDSS)

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

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

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 O’Riordan

MS Research Centre - Dundee

Clinical Research Facility Glasgow

LDN Trial

LDN Research Trust 2004

MS Society – rejection ! 2007

Chief Scientists Office - 2008

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

Mechanism of Action LDN

White blood cells produce two gases

Nitric Oxide Superoxide

Combine to produce peroxynitrite

Immune Function

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

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

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

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?

Crohn’s Disease

60 year old male patient

Severe crohn’s – nine bloody motions daily

Recent blood transfusion

19 colonoscopys

Started LDN 2007

Crohn’s 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