Multiple Sclerosis
Update on Ongoing Research
at the Jacobs MS Center
Bianca Weinstock-Guttman, MD,
Professor of Neurology
SUNY University at Buffalo,
UBMD Neurology
The
Atlas of MS
2013
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The Atlas of MS 2013 updates the
information that was collected in 2008 on:
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global epidemiology of MS
resources to diagnose
inform
treat
rehabilitate
support and provide services to people with
MS around the world.
KEY FINDINGS
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The estimated number of people with
MS has increased from 2.1 million in
2008 to 2.3 million in 2013.
This finding reinforces the conclusions of
the published epidemiological literature.
MS is found in every region of the world.
The 2:1 ratio of women to men with MS
has not changed significantly since 2008.
Atlas of MS
2013
More research is needed
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In relation to quality of life and
experiences of people with MS.
To measure the indirect costs of MS.
To understand sources and causes of
inequalities in access to support, health
care services and therapies.
To monitor MS and related disorders
through epidemiological studies and the
establishment of registries.
Getting to What Matters to
MS Patients
Environment
Healthy Brain
Infectious
Agents
Tissue Injury
Disease
Progression
Types of Multiple Sclerosis
Environmental Factors
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Epstein Barr Virus
Vitamin D
Smoking
Lipids
Cholesterol
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High cholesterol is a
known risk factor for
heart disease and
stroke
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HDL – High density
lipoprotein “Good”
cholesterol
LDL – Low density
lipoprotein “Bad”
cholesterol
21
20
C-Ring 18
11
19
1
2
3
A
4
12
5
7
6
B-Ring
D
14
8
10
17
13
9
22
15
23
24
25
27
16
26
Cholesterol
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Cholesterol is essential
75% of cholesterol is made in the liver
Remainder from the diet
Cholesterol is recycled and re-used
Cholesterol is the chemical building
block for hormones like cortisol,
estrogen, progesterone, testosterone
Cholesterol in the Brain
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The brain represents 2% of body
weight
Contains 25% of body cholesterol!
70% of brain cholesterol is in myelin
Mechanisms of Cholesterol
Action in MS
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Effects on brain vasculature
Effects on inflammation
Effects on neurodegeneration
Effects on vitamin D
Oxysterols, which are cholesterol
metabolites, have potent effects on the
immune system
Cholesterol and Vitamin D
HDL Cholesterol Affects
Vitamin D
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Higher HDL is associated with vitamin D sufficiency
Cholesterol & New Lesions
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Higher cholesterol is associated with formation of
new lesions
Cholesterol & Optic Neuritis
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Higher cholesterol is associated with poorer
recovery from optic neuritis
Lipoprotein Particles
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Lipids
Cholesterol
Proteins –
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Lipoproteins
Enzymes
Conclusions
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The role of cholesterol and lipids in MS
is not well understood
Cholesterol may have effects on MS
disease progression
Careful study is needed because the
cholesterol pathway is complex and
inter-connected with other
physiological functions.
Disease-Modifying Therapies
in Late Stages of Clinical Development
Oral Agents
 Dimethyl
fumarate (BG-12;
Tecfidera)
 Teriflunomide
(Aubagio)
 Fingolimod
(Gilenya)
 Ibudilast
Monoclonal
Antibodies
 Alemtuzumab
 CD20-Targeting
mAbs
•Ocrelizumab
• Ofatumumab
 Daclizumab
 Anti-Lingo1
Treatment Decisions:
Considering Benefits and Risks
Benefits
Meaningful impact
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Disease course
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MRI
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? > efficacy than
ABCR
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? Window of
opportunity
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Convenience
Risks
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ABCR = Avonex, Betaseron, Copaxone, or Rebif
Short-term safety
Long-term safety
Pregnancy issues
Many unknowns
Pediatric Network Research
Priorities
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Epidemiology
Genetics
Microbioma
Imaging
Neuropsychology
Treatment
Aging with MS
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MS beyond age 60
Knowledge and Understanding for
Clinicians and patients
Outcome – Disability (EDSS) and
Psychosocial Well-being (LIFEware)
DMT Safety and Tolerability
Discontinuation
30
Aging with MS
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In addition to demographics (DOB education
and marital status) Emphasis
 Comorbid conditions
 Insurance
 Quality of Life - Patient-reported activities
of daily living: Get up from sofa, climbing
stairs, standing, driving, vision, fatigue
 QoL – Psychosocial: Mood (depression,
anxiety, stress, loneliness, guilt, life
satisfaction)
31
Aging with MS – Potential Sample & Funding
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Secure funding to conduct
an additional
60-64
65-69
70-75
GE 76
AGE 2013
Reg with/without FUP
With FUP GE 2007
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Total
1,367
1,083
706
552
3,078
251
174
73
34
532
$100.00 Site Compensation for each patient ($ 50,000)
Multi-Site Start-up ($2,000 to 5,000)
Project Manager (PT 20,000)
Structured similar to PR Study - infrastructure in place
Projected funding need = $125,000
Blood and MRI – add to budget
32
Oligodendrocyte progenitor cells for the treatment of
chronic progressive multiple sclerosis
PI: Burk Jubelt
Co-PIs:
Steve Goldman
Andrew Goodman
Bianca Weinstock-Guttman
Goldman et al., Science, 2012
12 weeks
20 weeks
35 weeks
NF
MBP
hNuclei
Goal: To establish a human OPC-based therapeutic for
the treatment for secondary progressive multiple
sclerosis
Choice of target: Secondary progressive MS
Hypothesis: OPCs transplanted to patients with
immunologically quiescent secondary progressive
multiple sclerosis will experience
stabilized/improved neurological function, including
cognition and mobility via functional cell-mediated
effects
Fig. 1 Sites of neural stem cell direct implantation.
N. Gupta et al., Sci Transl Med 2012;4:155ra137-155ra137
Published by AAAS
Acknowledgments
Collaborators
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Murali Ramanathan,
PhD
Robert Zivadinov,
MD, PhD
Ralph Benedict, PhD
Richard Browne, PhD
Barbara Teter, PhD
David Hojnacki, MD
Channa Kolb, MD
Support
 National MS Society
 Department of Defense
 NYSTEM
 NIH
Biogen Idec
Novartis
Genzyme& Sanofi
TEVA
Questcor
Acorda
Training my body = training my brain!