Multiple SclerosisUpdate 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

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.

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.

Atlas of MS2013

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.

Getting to What Matters to MS Patients

Healthy Brain InfectiousAgents

Environment Tissue Injury

Disease Progression

Types of Multiple Sclerosis

Environmental Factors

Epstein Barr Virus Vitamin D Smoking Lipids

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

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

Cholesterol in the Brain

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

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

Higher HDL is associated with vitamin D sufficiency

Cholesterol & New Lesions

Higher cholesterol is associated with formation of new lesions

Cholesterol & Optic Neuritis

Higher cholesterol is associated with poorer recovery from optic neuritis

Lipoprotein Particles

Lipids Cholesterol Proteins –

Lipoproteins Enzymes

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.

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

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

Pediatric Network Research Priorities

Epidemiology Genetics Microbioma Imaging Neuropsychology Treatment

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

Oligodendrocyte progenitor cells for the treatment of chronic progressive multiple sclerosis

PI: Burk JubeltCo-PIs: Steve GoldmanAndrew GoodmanBianca Weinstock-Guttman

Goldman et al., Science, 2012

12 weeks

20 weeks

35 weeks

NFMBPhNuclei

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 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!