by Intracerebroventricular Delivery of VEGF in a

Rat Model of ALSEGF in a Rat Model of ALS

Treatment of Motoneuron Degeneration

What is ALS?• Amyotrophic lateral sclerosis,

also named Lou Gehrig’s 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.

A-myo-tropic

• 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

• 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

Symptoms of ALS include:

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

laughing

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.

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…

Hypothesis

• The authors hypothesized that intracerebroventricular delivery (i.c.v) of VEGF

• Would be a viable treatment for patients with ALS and neurodegenerative disorders in general.

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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