T HE P RESENT AND F UTURE OF MS Scott Belliston, DO Multiple Sclerosis Clinical Fellow

D ISCLOSURES None

N EW E RA 2010 Gilenya (Fingolimod) is approved by the FDA as the first oral therapy for RRMS 2012 Aubagio (Teriflunomide) is approved by the FDA 2013 Tecfidera (Dimethyl Fumarate) is approved by the FDA 2015 Lemtrada (Alemtuzumab) is approved by the FDA 2015 Glatopa (Glatiramer Acetate) the first generic approved by the FDA 2016 Zinbryta (Daclizumab) is approved by the FDA 14 DMDs for the treatment of RRMS

P RESENT Risk Diagnosis Treatment Symptom management

R ISK OF MS Many theories have been proposed CCSVI Environmental Viruses Genetic factors Vitamin D deficiency Melatonin Smoking Obesity Hormones Gut microbiota

D IAGNOSTIC TOOLS MRI Lumbar puncture Evoked potentials Optical Coherence Tomography

D ACLIZUMAB 14 th FDA approved medication for relapsing remitting MS Unique monoclonal antibody against IL-2 receptors 3 rd line agent due to risk of hepatotoxicity, autoimmune hepatitis and other immune mediated disorders Requires REMS certification for both physician and patient

REMS Risk Evaluation and Mitigation Strategy FDA can require a drug to have a REMS program Manufacturers required to follow guidelines to ensure that the benefits of a medication outweigh it’s risks.

O CRELIZUMAB Monoclonal antibody that targets B cells May be the first of many drugs for progressive MS Granted Breakthrough Therapy by FDA Clinical trials for progressive MS High dose biotin Tcelna for secondary progressive

L AQUINIMOD Oral medication Reduces leukocyte migration to the CNS Trials ongoing for RRMS, PPMS, and SPMS Higher dose trial suspended due to cardiovascular events

I BUDILAST Oral medication Used as an anti-inflammatory drug in Japan for treating neuropathic pain Appears to have neuroprotection Ongoing trials for SPMS and PPMS Was granted a fast track by the FDA

S IPONIMOD Oral medication Selective sphingosine-1-phoshate receptor modulator Just announced positive outcome in phase III trial for reduction in disability progression compared to placebo Further results to come at ECTRIMS

A NTI L INGO AND R EMYELINATION Unfortunately Anti Lingo failed outcome measures in phase 2 studies This is one of many drugs to come with goal of remyelination

M ORE A GGRESSIVE T REATMENTS We are getting better at treating RRMS We are seeing more adverse events More immunosuppression with subsequent infections including PML

S YMPTOM M ANAGEMENT Ampyra (dalfampridine) “the walking drug” approved in 2010 First medication to get FDA approval specifically for symptom management in MS It works by helping nerve transmission across demyelinated nerves

S YMPTOM M ANAGEMENT Incontinence Botox Vesiflo Video

T HE F UTURE What does the future of MS look like Causes of MS Cure of MS Prevention of MS

M EDICINE IS RAPIDLY CHANGING

T ECHNOLOGY IS PUSHING US FORWARD Video

Wheelchair Video 2 Wheelchair Video Video

W HAT CAUSES MS? More risk factors to be found Better understanding of the dysfunctional immune system More gene testing and understanding the genetics of MS

I NCIDENCE Increasing overall not just improved diagnosis Charcot thought that it was more common in men In the early 1900s it was thought to be equal in men and women In the 1970’s it was 2:1 women:men Now it is close to 3:1

D IAGNOSIS IN THE F UTURE Average time to diagnosis quicker Blood tests to confirm diagnosis Use of MR spectroscopy, Functional MRI, or PET scans

B IOMARKERS As we now have 14 DMDs and all have potentially significant side effects and some work better in one person than another. Biomarkers including blood, CSF, or genetic markers that will help guide us in choosing the right DMD for a patient.

C LEMASTINE Anti histamine showing evidence of stimulating myelin repair of the optic nerves Why Clemastine???? Jonah Chan PhD Video

S TEM CELL THERAPIES The NMSS is currently supporting 12 trials for stems cells in MS They have supported 68 trials over the last 10 years Currently no treatment with stem cells therapy has been approved Mesenchymal stem cells Autologous stem cell transplantation Improvement in safety and efficacy

H ALT - MS High-Dose Immunosuppressive Therapy and Autologous Hematopoietic Cell Transplantation for Relapsing-Remitting Multiple Sclerosis 25 patients were enrolled 24 received the treatment 5 year trial 1 patient died 70% remained free of disease activity at 3 years with no relapses, no new MRI detected lesions, and no signs of progression 40% experienced a reduction in their disability

T REATMENTS We need treatments with less risk and more benefit More affordable medications Generic medications Vaccination for JC virus, prevent possibility of PML Medications for progressive MS Medications for remyelination

S YMPTOM M ANAGEMENT Better medications for symptoms Medications specifically for fatigue Walking Pain Incontinence Bardia Nourbakhsh, MD

A C URE This is a real possibility What is a cure More than stopping progression We aren’t there yet

P REVENTION Ability to predict who is at risk of MS Vitamin D supplementation Melatonin Vaccination?

A CKNOWLEDGEMENTS

Q UESTIONS