Multiple Scleroris Lyle Wiemerslage, PhD

Typical Clinical Vignette Female in her late 20’s About twice as common in women Genetic susceptibility Geography, more common far from equator First symptom optic neuritis Loss of vision OD OS

Molecular Description https://vimeo.com/68315620

Clinically Isolated Syndrome (CIS) versus MS

Treatments for MS Interferon α and β Glatiramer acetate NAbs Glatiramer acetate Molecular decoy? Monoclonal antibodies Natilizumab Alemtuzumab

Oral Medications Fingolimod Teriflunomide Dimethyl fumarate

Making an animal model for MS + Freund's adjuvant

Clinical Trials for MS clinicaltrials.gov Outside of academia

Lifespan of a drug

Preclinical Basic science No Observable Adverse Effect Levels (NOAEL) Academic work Drug discovery High throughput screening No Observable Adverse Effect Levels (NOAEL) Investigator's brochure (IB) Animal studies Adverse effects

Finding Effective Treatments IFN-γ Thought it may work as antiviral, MS patients also had decreased production of it (false)

Measuing Symptoms Number of relapses MRI Placebo effect MRI Expanded Disability Status Scale (EDSS) multiple sclerosis functional composite (MSFC)

Contract Research Organiztion ”A multicenter, double-blind, randomized, placebo-controlled, parallel group, efficacy and safety trial of *drug* in patients with...”

Economics of Clinical Research US patent lasts 17 years Development to approval takes ≈10 years Research is expensive! 80.000 to 400.000 kr per patient Orphan drugs Price of medication can be 400.000 kr/year/pt

More Information Curing MS: How Science is Solving the Mysteries of Multiple Sclerosis Howard Weiner Blog for clinical research: http://pipeline.corante.com/