by%20%20Intracerebroventricular%20Delivery%20of%20VEGF%20in%20a%20%20Rat%20Model%20of%20ALSEGF%20in%20a%20Rat%20Model%20of%20ALS

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Treatment of Motoneuron Degeneration

• by Intracerebroventricular Delivery of VEGF in
  a Rat Model of ALSEGF in a Rat Model of ALS

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What is ALS?

• Amyotrophic lateral sclerosis, also named Lou
  Gehrigs disease after the famous baseball
  player, is a paralyzing and deadly disease that
  takes the lives of individuals between 3 and 5
  years of onset. This progressive
  neurodegenerative disorder affects nerve cells of
  the brain and spinal chord. According to U.S.
  population studies, just over 5,600 people in the
  U.S. are diagnosed with ALS each year.

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A-myo-tropic

• The term A-myo-tropic stems from Greek
  vernacular
• A means no
• myo is used in reference to muscles
• trophic is a term that means nourishment

• Put together, this word means no muscle
  nourishment. Muscles that are not properly
  nourished atrophy and causes the lateral portions
  of the spinal chord to become scarred, which is
  sclerosis. Motoneurons that are subjected to
  degeneration are not able to send electrochemical
  impulses through motorunits, which usually causes
  muscle movements

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Symptoms of ALS include

• Muscle weakness
• Dysarthria
• Dysphagia
• Fasciculation
• Difficulties swallowing and breathing
• Uncontrollable bouts of crying and laughing

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The Medical Challenge

• There is no known cure for ALS, and as of yet,
  researchers do not fully understand the
  mechanisms that cause the degeneration of
  motoneurons due to ALS. However, a correlation
  has been made between mutations in superoxide
  dismutase 1(SOD1) (human and rat) and motoneuron
  degeneration. For this reason, rats expressing
  SOD1 (termed SOD1 G93A mice) are used as a
  standard model to assess drug candidates.

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The Medical Challenge

• It is known by the authors that low levels of
  Vascular endothelial Growth Factor (VEGF) in
  gene-targeted mice leads to motoneuron
  degeneration that is similar to ALS in humans.
  (insert motoneuron slide)
• Previous knowledge has also indicated that that
  VEGF delays ALS onset and increases the survival
  rate of SOD1 G93A rats.

• Given these findings

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Hypothesis

• The authors hypothesized that intracerebroventricu
  lar delivery (i.c.v) of VEGF
• Would be a viable treatment for patients with ALS
  and neurodegenerative disorders in general.

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What is VEGF?

• Primarily known for its angiogenic
  properties, Vascular Endothelial Growth Factor is
  an extra-cellular signaling protein that acts as
  a cell-specific growth factor. VEGF belongs to a
  group of endothelial mitogens that are related to
  platelet-derived growth factor.

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KEY EXPERIMENTS
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