Download Idiopathic Overactive Bladder script for translation

Idiopathic Overactive Bladder script for translation ENGLISH (video 2)
Narration
Scene 1
Botox is a unique biological. It has been licensed for a broad range of therapeutic conditions where
over-activity in sensory and/or motor pathways is key to the pathophysiology.
Scene 2
One of these conditions is idiopathic overactive bladder, which is a urological disorder defined as
urgency with or without urgency incontinence usually accompanied by frequency and nocturia.
Scene 3
As the bladder fills, its wall begins to stretch, triggering the activation of receptors found within the
bladder urothelium, sub urothelium and detrusor smooth muscle.
Scene 4
Activation of these receptors sends signals along afferent neurons to the central nervous system
which in turn produces efferent signals which are relayed via the parasympathetic nervous system to
the detrusor smooth muscle that lines the bladder; causing it to contract and voiding to occur.
Scene 5
Stimulation of both sensory afferent and motor efferent neurons causes vesicles, including those
containing the neurotransmitters CGRP, acetylcholine and ATP to dock with the nerve membrane.
Docking is facilitated by the SNARE complex, composed of attachment proteins including SNAP25,
which also help the vesicle fuse with the membrane to release these neurotransmitters.
Scene 6
In sensory neurons, neurotransmitters bind to receptors found on the postsynaptic membrane,
which activate further afferent pathways to the central nervous system. The brain then activates the
relevant motor neurons in response.
Scene 7
In motor neurons acetylcholine binds to receptors found on the surface of detrusor smooth muscle
cells, resulting in subsequent muscle contraction.
Scene 8
The aetiology of overactive bladder is complex and is yet to be fully elucidated but both afferent and
efferent pathways as well as a multitude of neurotransmitters are thought to be involved.
Scene 9
Therefore, treatments which target both afferent and efferent pathways may prove beneficial in
resolving the symptoms associated with overactive bladder.
Scene 10
Botox is injected directly into the detrusor muscle in the bladder wall. Some time after injection, the
Botox core 150-kilodalton molecule (comprising of a heavy chain and light chain) dissociates from
the surrounding protective accessory proteins.
Scene 11
The binding domain of the BOTOX core molecule is the C-terminal portion of the heavy chain, which
interacts with receptors on the nerve terminal. The Botox protein then enters the nerve through a
process known as receptor mediated endocytosis and is now encapsulated within a membranous
vesicle inside the cell.
Scene 12
The light chain is now released into the cytoplasm of the nerve terminal.
Scene 13
Once released the Botox light chain can then bind and cleave SNAP-25, an essential component of
the SNARE complex. In doing so, it prevents the release of neurotransmitters from both sensory and
motor neurons, resulting in reductions in the sensation of urgency and urinary incontinence
episodes.
Scene 14
Botox synergistically affects both afferent and efferent pathways involved in the pathophysiology of
overactive bladder through a targeted sensorimotor action.
Scene 15
As a result, Botox has been shown to improve all bladder symptoms associated with overactive
bladder.
On Screen text
Idiopathic Overactive Bladder
Bladder
Normal Bladder Function
Sensory Neurons
Detrusor Smooth Muscle
Neurotransmitters
SNARE Complex
Postsynaptic Membrane
Receptor
Afferent
Efferent
How BOTOX® Works
(Botulium toxin type A)
100kDa Heavy Chain
50kDa Light Chain
Snap-25
References