multiple sclerosis update on ongoing research at the jacobs ms center bianca weinstock-guttman, md,...
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Multiple SclerosisUpdate on Ongoing Research at
the Jacobs MS Center
Bianca Weinstock-Guttman, MD,Professor of Neurology
SUNY University at Buffalo,UBMD Neurology
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The Atlas of MS
2013
The Atlas of MS 2013 updates the information that was collected in 2008 on: global epidemiology of MS resources to diagnose inform treat rehabilitate support and provide services to people with
MS around the world.
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KEY FINDINGS
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.
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Atlas of MS2013
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More research is needed
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.
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Getting to What Matters to MS Patients
Healthy Brain InfectiousAgents
Environment Tissue Injury
Disease Progression
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Types of Multiple Sclerosis
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Environmental Factors
Epstein Barr Virus Vitamin D Smoking Lipids
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Cholesterol
High cholesterol is a known risk factor for heart disease and stroke HDL – High density
lipoprotein “Good” cholesterol
LDL – Low density lipoprotein “Bad” cholesterol
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Cholesterol
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
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Cholesterol in the Brain
The brain represents 2% of body weight
Contains 25% of body cholesterol! 70% of brain cholesterol is in myelin
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Mechanisms of Cholesterol Action in MS
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
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Cholesterol and Vitamin D
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HDL Cholesterol Affects Vitamin D
Higher HDL is associated with vitamin D sufficiency
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Cholesterol & New Lesions
Higher cholesterol is associated with formation of new lesions
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Cholesterol & Optic Neuritis
Higher cholesterol is associated with poorer recovery from optic neuritis
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Lipoprotein Particles
Lipids Cholesterol Proteins –
Lipoproteins Enzymes
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Conclusions
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.
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Disease-Modifying Therapies in Late Stages of Clinical Development
Oral AgentsMonoclonal Antibodies
Dimethyl fumarate (BG-12; Tecfidera)
Teriflunomide (Aubagio)
Fingolimod (Gilenya)
Ibudilast
Alemtuzumab
CD20-Targeting mAbs
•Ocrelizumab
• Ofatumumab
Daclizumab
Anti-Lingo1
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Benefits Risks
Meaningful impact Disease course
MRI ? > efficacy than
ABCR ? Window of
opportunity Convenience
Treatment Decisions: Considering Benefits and Risks
Short-term safety
Long-term safety
Pregnancy issues
Many unknowns
ABCR = Avonex, Betaseron, Copaxone, or Rebif
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Pediatric Network Research Priorities
Epidemiology Genetics Microbioma Imaging Neuropsychology Treatment
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Aging with MS
MS beyond age 60 Knowledge and Understanding for
Clinicians and patients Outcome – Disability (EDSS) and
Psychosocial Well-being (LIFEware) DMT Safety and Tolerability Discontinuation
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Aging with MS
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)
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Aging with MS – Potential Sample & Funding
Secure funding to conduct an additional
$100.00 Site Compensation for each patient ($ 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
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AGE 2013 60-64 65-69 70-75 GE 76 Total
Reg with/without FUP 1,367 1,083 706 552 3,078
With FUP GE 2007 251 174 73 34 532
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Oligodendrocyte progenitor cells for the treatment of chronic progressive multiple sclerosis
PI: Burk JubeltCo-PIs: Steve GoldmanAndrew GoodmanBianca Weinstock-Guttman
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Goldman et al., Science, 2012
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12 weeks
20 weeks
35 weeks
NFMBPhNuclei
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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
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Fig. 1 Sites of neural stem cell direct implantation.
N. Gupta et al., Sci Transl Med 2012;4:155ra137-155ra137
Published by AAAS
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Acknowledgments
Collaborators 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
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Training my body = training my brain!