What is Multiple Sclerosis?? a disease that affects the

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Interferon for Multiple Sclerosis
Alla Mant Monica Awada Zainab Jishi
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What is Multiple Sclerosis??

• a disease that affects the central nervous system
  and results in the progressive loss of certain
  body functions and physical abilities.

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How does it work??

• Multiple Sclerosis attacks the central nervous
  system, which consists of the brain and spinal
  cord

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The Breakdown
A fatty substance called Myelin covers each nerve
fiber insulating them and helping with the
transmission of nerve impulses between the brain
and other parts of the body.
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These impulses , or messages, control muscle
movements.
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The destruction of the myelin sheath leads to
impaired communication between nerve cells and
neurological symptoms such as abnormal
sensations, vision problems , and weakness.
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DANGER!!
The attack on the immune system kills axons,
which can also lead to permanent loss of
function.
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Immune system T cells normally in the bloodstream
become activated against components of the brain
myelin. They cause local inflammation in
scattered regions of the brain and spinal cord
once they cross the barrier between the
bloodstream and CNS.
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• This could result in damage and lost fibers.
• Nerves can regain myelin, but process is not fast
  enough to avoid the deterioration that occurs in
  MS
• Astrocytes form scars where myelin formerly
  existed
• Inflammation, loss of myelin, and nerve fibers,
  and the following scarring result in reduced
  transmission of nerve signals within the CNS.
• Types of symptoms and severity vary widely due to
  the location of the scar tissue and extent of
  demyelination

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The Diagnosis
There are four courses that MS progression can
take

• Relapsing Remitting
• Secondary Progressive
• Primary Progressive
• Progressive relapsing

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Relapsing Remitting
Exacerbations flare-up or attack of symptoms
such as numbness or tingling of hands and feet
that typically last for a few weeks
exacerbations come and go throughout the disease
course of MS.

• Occur by an area of inflammation in the nerves of
  the brain and spinal cord system after
  demyelination
• Disease does not worsen in periods between the
  attacks

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Secondary Progressive

• Begins with relapsing remitting but evolves into
  progressive disease
• Can occur over a long stretch of time

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Primary Progressive

• Gradual but steady progression of disability
• No obvious relapses and remissions
• 15 of people with MS
• Develop disease after 40 years of age

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Progressive Relapsing

• Least common form
• Steady progression in disability with acute
  attacks
• There may be no recovery after attacks

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Symptoms
Three categories
Primary direct result of damage (weakness,
tremors, tingling, numbness, paralysis and
bladder/bowel problems) Secondary result from
primary (Paralysis leads to bedsores and
bladder/urinary incontinence problems) Tertiary
Social, psychological, vocational
complications (Depression very common)
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Spasticity

• The nerves in the CNS have important functions in
  the motor control over muscles demyelination can
  affect these fibers and cause weakness in
  different muscle groups
• Complex system of control allows some muscles to
  contract and some to relax with movement
• They inhibited some and contract others to
  disrupt CNS
• Results in the simultaneous contraction of many
  muscles, both agonists and antagonists, causing
  the limb to feel tight

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Possible vs. Definite MS

• General Physical
• History of all complaints of patients general
  health
• MRI (Magnetic Resonance Imaging)
• Detects patchy areas of change in the CNS

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Continued.

• CSF (Cerebrospinal fluid)
• Surrounds the brain and spinal cord and fills
  the cavities within CNS
• Fluid examined for cells, proteins, and
  electrolytes
• Proteins examined for presence of oligoclonal
  bands.
• NOT COMMON IN EARLY CASES

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Three Categories of Treatment

• Underlying Course of the Disease
• Treatment of Exacerbations
• Specific MS symptom treatment

• Treatment of exacerbations must be done with
  corticosteroids to manage acute attacks. These
  are substances related to hormones that are
  produced by adrenal glands. Help to reduce
  swelling and inflammation in the plaques of
  demyelination.

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Treatment of Underlying Disease
Interferons vs. Glatiramer Acetate

• Copaxone is a substitute antigen that mimics
  myelin basic protein. It inhibits the CNS immune
  reactions that are responsible for tissue damage.
  
• Given subcutaneously daily injection
• Reduces number of attacks and brain lesions seen
  on MRI patients
• No flu-like side effects associated with
  interferons

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Interferons

• Discovered in 1957
• Significant antiviral agents
• phenomenon where one infection with one virus
  interferes with a subsequent infection with
  another virus

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What are they??
A protein substance naturally produced in the
body and believed to function to modulate the
immune system. Interferons interact with
receptors on non-infected cells to promote the
synthesis of antiviral proteins that prevent
further infection. They belong to Cytokines,
which are hormones of the immune system.
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Beta Interferon

• Beta interferon-1a
• Avonex administered weekly by an
  intramuscularly injection (2003)
• Rebif administered subcutaneously three times
  a week (2002)
• Beta interferon-1b
• Betaseron administered subcutaneously every
  other day (1993)

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• Early and aggressive treatment with immune
  stimulating interferons can delay or possibly
  even prevent crippling symptoms of MS

MS has at least two phases
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1.) Relapsing-Remitting (R/R) Phase Known for
episodes and flare-ups followed by periods of no
or mild symptoms. This is caused by
inflammation. 2.) Progressive Phase The gradual
but ongoing breakdown of nerve cells. The
inflammation decreases but the disease worsens.
Approximately 50 of people with MS enter the
secondary phase 10 years after R/R phase begins
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Common Side Effects

• Typical Flu-like symptoms
• headache, nausea, and fever
• muscle aches
• Chills
• Irritation at the injection site

Alcohol and exposure to sunlight may irritate
side effects
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CURRENT STUDIES
CHAMPIONS Avonex altered long-term course MS in
patients who began treatment immediately after
initial attack 35 decrease in the rate of
developing second attack 42 reduction in new or
enlarging T2 hyper intense lesions
Avonex associated with fewer neutralizing
antibodies. Binding antibodies decrease the
medications efficacy. They hasten the drugs
removal from the bloodstream.
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June 18th 2003

• EVIDENCE Showed that patients on Avonex who
  converted to Rebif showed signs of relapse
  reduction
• Patients taking Rebif had fewer active lesions
  per MRI scan for all studied activity

July 21st 2003

• QUASIMS Higher doses and frequencies of
  interferon beta are not necessarily better with
  comparable disease progression
• Annual Relapse rates
• Avonex - .52
• Rebif - .69

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NEW STUDIES
The high hydrophobicity and thus poor solubility
of interferon-beta is problematic for production
and clinical efficacy of the product. The protein
is produced in bacterial or mammalian cells by
genetic engineering.
Hydrophobicity Engineering
German Fraunhofer Institute for Interfacial
Engineering and Biotechnology designed variants
of recombinant human interferon-beta whose
solubility is improved. The goal was to reduce
the clustering between the molecules in order to
increase the protein yield and thus
pharmacological effectiveness
June 2003
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The Future of Interferons for MS

• In Aug. 2003 Cleveland Clinic announced Avonex
  Combination Trials.
• Compare relapse rates and brain atrophy over 2
  years for four combination treatments
• Approximately 900 patients will be enrolled and
  divided into four groups , with each receiving a
  different therapy

This could be a huge breakthrough in the fight
against progression in MS..