Multiple Sclerosis & Treatment of Progression with Interferon-Beta-1a

What is Multiple Sclerosis? Most commonly defined as an autoimmune disease that affects the CNS Characterized by the loss and/or damage of the myelin sheath Loss of myelin sheath results in the inability of neurons to transmit neural signals properly, causing the many symptoms of MS Unpredictable and no known cures Axon can be damaged as well

Anatomy of the Neuron

Four Major Varieties of MS Relapsing/remitting (RRMS) Characterized by periods of flare-ups and remission Accounts for 85% of MS patients Primary Progressive (PPMS) Slow continuous worsening of disease from onset Only about 10%

Four Major Varieties of MS (cont.) Secondary Progressive (SPMS) Initial period of relapsing-remitting, then steady worsening of disease 50% of patients diagnosed with RRMS develop into this variety within 10 yrs without drug treatment Progressive Relapsing (PRMS) Steady worsening with acute relapses Different from RRMS in that disease progresses during relapses Only about 5 %

What Causes MS? Not exactly known Several theories Most common—myelin damage results from abnormal response in the immune system T cells (type of white blood cell) attack myelin Though to be triggered by environmental and/or genetic factors

Many other theories MS is pathogen-mediated Genetics Research suggests Chlamydia Pneumoniae and other pathogens may trigger MS Genetics Identical twin studies-> one has MS, other has 30% chance No specific gene/s found yet Most likely involves a combination

MS Geography Typical onset between ages 20-50 Reduces life expectancy by about 10-15 yrs About ½ patients survive 30+ yrs from onset Affects 2-3 times as many women than men Research suggests that genetic factors play a role More common among people of European descent About 400,000 Americans have MS

Symptoms of MS Wide variety due to nature of disease Different classifications of symptoms Visual Motor Sensory Cognitive Coordination/Balance Bowel, Bladder, and Sexual Others

Diagnosis of MS No single test for diagnosing MS Usually diagnosed when all other possibilities ruled out Many tests Medical history Nervous system functioning MRI, Evoked potential tests, spinal tap

Basic “Rule” for Diagnosis Est. by committee sponsored by NMSS in 1965 Must have BOTH of the following: Evidence of myelin loss in at least 2 areas occurring in different places at different times Any other diseases that could account for the above have been ruled out Revised in 1983 by Poser to take into account advances in MRI technology

Treatments for MS No known cure Treatments involve relieving the symptoms or slowing the progression of the disease These are mostly drug treatments Also CAM’s- Complementary and Alternative Medicine

CAM’s Used with or instead of conventional drug treatments Some include Acupuncture Herbal medicine Yoga Relaxation techniques Hypnosis

Conventional Drug Treatments Disease-modifying drugs* ABC Treatments Chemotherapeutic Agents Corticosteroids & ACTH Drugs that help with symptoms Wide variety from anti-depressants (depression) to laxatives (bowel dysfunction) to anti-convulsants (pain/altered sensations) * Hard to tell if drug is modifying the course of the disease because the disease is so unpredictable…

ABC Treatments Most popular drug treatments for modifying course of disease Work by regulating aspects of the immune system ABC refers to the 3 major brand names of this category of drugs: Avonex, Betaseron/Betaferon, and Copaxone Also now added Rebif and Novantrone

ABC Treatments Cont. Interferon beta-1a Interferon beta-1b Avonex, Rebif Interferon beta-1b Betaseron/Betaferon Glatiramer acetate Copaxone Mitoxantrone Novantrone

What are Interferons? Occur naturally in human body Proteins that prevent viral multiplication by stimulating the production of antiviral proteins in normal cells Interferon-alpha, Interferon-beta, and Intereron-gamma

Avonex Interferon-beta-1a Used for RRMS and SPMS w/relapses Produced by recombinant DNA technology using genetically engineered Chinese Hamster Ovary cells into which the human interferon beta gene has been introduced The resulting amino acid sequence is identical to human interferon-beta

Avonex Mechanisms by which it exerts it effects not fully understood Pharmacokinetics in MS patients not evaluated Recommended dosage of 30 mcg to be injected intramuscularly one weekly Not recommended subcutaneously- adverse reactions mainly at site of injection* No known interactions with other drugs Safety of doses above 60 mcg has not been evaluated-> do not know lethal dose -Pharmacokinetics is what body does to drug- how it is absorbed, distributed, eliminated, etc -Has been evaluated in healthy patients -Injected because it’s a protein..if pill stomach would break it down * Inflammation, atrophy, and hemmorhage

Current Avonex Research Avonex fairly new Lots of research being done, few consistent findings yet Most research with Avonex focuses on: Comparison with other drugs of its type Testing properties of the drug by altering dosages,etc. Seeing how well drug modifies disease course in placebo studies

Future Research on MS Finding the cause Stopping/slowing progress of disease Repairing damage already done Remyelination Better ways of treating symptoms Focusing on the social implications

Recommended Websites to Learn More http://www.avonex.com http://www.nationalmssociety.org