Wisconsin Womens Health: Multiple Sclerosis Prof. Colleen E. Hayes - - PowerPoint PPT Presentation

Wisconsin Women’s Health: Multiple Sclerosis

• Prof. Colleen E. Hayes

Department of Biochemistry University of Wisconsin-Madison

Chris Pe ggy De ana Sue A nn Colle e n

Credit: Seattle Children’s Hospital

Multiple Sclerosis is an autoimmune disease

Healthy nerve fiber with an intact myelin sheath Demyelinated nerve fiber with autoimmune lesions

Credit: Seattle Children’s Hospital

For every disease there is a single key mechanism that dominates all others. If

• ne can find it, and then think one’s way

around it, one can control the disorder

• Lewis Thomas

Knowing the single key mechanism in MS enabled researchers to control the disease

 MS patients who took Agent X weekly for a year had

85% fewer new MRI lesions

Soilu-Hanninen et al. J Neurol Neurosurg Psychiatry 83:565, 2012

Multiple Sclerosis Trust UK

Optic neuritis and multiple sclerosis

 20% of MS patients experience painful visual loss as a

first symptom

 50% of optic neuritis patients develop MS

Normal vision Optic neuritis

Derakhshandi et al. 2013 Acta Neurologica Belgica 113:257-263

Knowing the single key mechanism in MS enabled researchers to control the disease

BRAIN MRI PLACEBO AGENT X Black holes 1.64 0.15 New T2 lesions 2.63 0.64 New Gad lesions 1.36 Cortical lesions 3.36 1.08 Juxtacortical lesions 2.82 0.69



Optic neuritis patients were randomized to receive a placebo or Agent X in a double-blind clinical study



Brain scans were performed at the beginning and end of the study



Agent X significantly reduced black holes, lesions, and progression to MS

Derakhshandi et al. 2013 Acta Neurologica Belgica 113:257-263

Discovering the single key mechanism that enables us to control multiple sclerosis

1997: Scientific Reasoning

 Agent X is an environmental factor that determines

whether people with genetic risk factors will develop multiple sclerosis

 If we aspire to control multiple sclerosis, we must

discover what Agent X is and how it works

Individuals at risk Environmental risk factor

10dailythings.com Aug 16, 2008

The risk of multiple sclerosis varies inversely with latitude and sunlight

 0o latitude: <2 MS cases/105 population  >55o latitude: >400 MS cases/105 population

Sir Donald Acheson

Agent X is something we produce when we expose our skin to sunlight

Winter Summer

Oslo: 136 MS cases/105 people

The risk of multiple sclerosis varies inversely with fish consumption, overcoming a lack of sunlight

Fish consumption

Grytten et al. 2006 Neurology 66:182-186 J/m2

Finnmark County: 73 MS cases/105 people

Swank et al. 1952 N Engl J Med 246:722-728

Agent X is something we ingest when we consume fish

“In Cod We Trust” -George Ebers

“It is our hypothesis that one crucial environmental factor is the degree

• f sunlight exposure catalyzing the

production of vitamin D3 in skin, and, further, that the hormonal form

• f vitamin D3 is a selective immune

system regulator inhibiting this autoimmune disease”

Hayes, C.E. et al.. 1997, Fed. Proc. Soc. Exp. Biol. Med. 216:21

How does vitamin D3 reduce brain lesions?

 The inflamed brain produces calcitriol, the

hormonal form of vitamin D

astrocytes Blood vessel Calcitriol Invading T lymphocytes Invading immune cells

 Calcitriol causes invading immune cells to die

 The non-inflamed brain repairs damaged tissue

One dose of the vitamin D hormone reversed demyelinating disease in rodents

Disability Days

Treatment

Placebo Calcitriol

No disease Diseased, placebo Diseased, calcitriol Nashold et al. J. Neuroimmunol. 263, 64-74, 2013

Optic nerve sections

Vitamin D3 confers health benefits beyond multiple sclerosis

 Type 1 diabetes  Infectious disease  All types of cancer including breast cancer  Neurodegenerative disease including Alzheimer’s

Disease

 Neuropsychiatric disorders including depression  Cognition, memory, and learning  Bone health

Would early, substantial, and consistent vitamin D3 supplementation prevent a significant proportion of multiple sclerosis cases?

Special thanks for a quarter century of collaboration

• Prof. George Ebers

Chair Emeritus Department of Neurology Oxford University Oxford, UK

• Ms. Faye Nashold

Department of Biochemistry University of Wisconsin Madison, WI Sir Donald Acheson Emeritus Chief Medical Officer United Kingdom

Research support: National Multiple Sclerosis Society, T. Wolfe and P. Powers