Advances in MS ResearchSouth Central Annual Meeting

Bruce Bebo, PhDExecutive Vice President, Research

1. Progression of MS2. Key advances MS research: Nervous system

repair, progressive MS and wellness3. What the Society doing to find solutions for

people living with all forms of MS?

Overview

Multiple Sclerosis ProgressionIdentifying targets to slow or stop the progression of disability

Chronic Lesion

Progressive MS is Characterized by Degeneration of Nerves and Nerve Fibers

Possible Mechanisms of Neurodegeneration in MS

• Dysfunction in myelin repair

– May deny the neurons survival signals– Leaves the neurons vulnerable

• Neuronal cell damage induced by:

– Excitotoxicity– Oxidative stress– Loss of nerve cell support factors/receptors – Energy failure

Nervous System RepairScience fiction becomes reality!

The Nervous System Can Repair Itself!

• Oligodendrocyte Progenitor Cells (OPC’s)

• 5-8% of all the cells in the nervous system

• Tremendous ability to induce “natural repair”

Promoting Natural Myelin Repair with Anti-LINGO

Mi, et al., Nature Medicine, 2007; 13(10):1228

• LINGO-1 inhibits remyelination• Anti-LINGO-1 promotes remyelination in an MS-like disease in mice• Shown to be safe in early human trials• Early evidence for efficacy in optic neuritis• Currently in a phase II trials in RRMS

Repurposing FDA Approved Drug to Promote Natural Repair

Mei, F., et al., Nature Medicine.2014, August 20(8):954

Control

Control

Treated

Treated

Transplantation Oligodendrocyte Progenitor Cells: A Promising Approach for MS Repair

Windrem, and Goldman, Cell Stem Cell. 2013 Feb 7;12(2):252

Progressive MSNew Strategies to slow down or stop damage to the nervous system

Agents of Interest for Neuroprotection in MSMechanism of Action Agents 

Sodium channel blockers Lamotrigine, amiloride, phenytoin, flecainide, carbamazepine

Calcium channel blockers Nimodipine, nifedipine, ryanodine, CYLA, bepridil

Glutamate antagonists Riluzole, NBQX, talampanel,memantine

Growth factors Erythropoietin, rhIGF

NO blockers Furoxan

Sex hormones Estriol, testosterone

Phenols  Resveratrol, epigallocatechin‐3‐gallate

Statins  Simvastatin, atorvastatin

Immunophilin ligands  Cyclosporin A, FK506, rapamycin

PPARg agonists Pioglitazone 

Agents with pleiotropic effects

Ibudilast, minocyclin, co‐Q10, galectine‐1, vitamin D

Simvastatin (Zocor) Trial in Secondary Progressive MS

43% decrease in brain atrophy

Significant improvement in

disability

Ongoing Clinical Trials of Neuroprotective Agents for Progressive MS

• US-based Phase II trial in SPMS/PPMS (250 participants)

• 2 arms: ibudilast, placebo• Outcomes: Rate of nervous system atrophy at

2 years

• UK-based Phase II trial in SPMS (440 participants)

• 4 arms: riluzole, amiloride, ibudilast, placebo• Outcomes: Rate of nervous system atrophy

MissionTo expedite the development of therapies for effective

disease modification and symptom management in progressive MS

An expanding alliance of MS organizations from around the world

www.endprogressivems.org

Lifestyle and WellnessStrategies for Improving the lives of people living with MS NOW!

Driving Solutions: Wellness/Rehab Research-- Society investments have resulted in progress on many fronts, including:

• Evidence for improvement of MS symptoms such as fatigue and cognition by aerobic exercise

• Development of rehabilitation strategies to improve balance and walking

• New strategies for improving cognitive function and psychosocial wellness

• Connection between MS risk and low vitamin D, dietary salt, obesity, and smoking

Wellness: What’s the Best Approach?

• Insufficient evidence available to establish effectiveness in MS of• Diet• Supplements• Exercise• Mindfulness

• Established a workgroup of wellness thought leaders to review the current evidence

• Identify gaps in knowledge

• Develop a research strategy

• Develop a Society-wide approach to wellness programming

Society Wellness Strategy

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• Finding solutions for people with MS is the Society’s Highest Priority

• The Society has invested nearly $870 million in research

• Fueling research through increased investment

– 2014: $50.6 million for 380 new/ongoing projects

– 2015: $52+ million

• The Society funds more research and impacts more lives than any other MS organization in the world

Stop, Restore, End – For Everyone with MS

Stop

Restore

End

• Comprehensive and Collaborative– Pursue all promising paths, wherever they exist– Expand/strengthen MS research globally– Remain nimble to seize promising new

opportunities• Investigator-initiated and targeted• Centralized peer review, funding and

stewardship• Fund worldwide – no boundaries

Research Strategies