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0:00
Hello, today we will be
discussing the disease mechanisms
of Type 3 Gaucher disease and the
potential therapeutic targets.
In part one of my presentation,
we discussed the enzyme defect,
genetics as well as
the phenotypes and
the natural history.
0:24
Today we will be discussing
the current treatment landscape
of type 3 Gaucher disease,
outcomes of enzyme
replacement therapy,
future treatment options,
mechanisms of disease,
novel therapeutic targets,
biomarkers as well
as unmet needs.
0:47
To understand how to
develop a roadmap
from the understanding of
disease mechanisms to therapy,
we need to understand
the pathogenic cascades.
Understand whether there is
selective neuronal vulnerability
to GBA mutation.
What are the unifying
disease mechanisms due to
the enzyme defect?
Whether neuroinflammation
has an important role.
Because in the
previous presentation,
we discussed how potent
the inflammatory lipids
that accumulate in
Gaucher disease are.
Whether there are any
genetic modifiers.
Whether neurological disease
once established is reversible.
What is the current
therapeutic landscape?
1:39
Just to recap from my
previous presentation,
Gaucher disease is an inborn
error of metabolism due to
biallelic mutations
in a lysosomal enzyme
called acid β-glucosidase.
When this is deficient,
it leads to the accumulation
of the substrate shown here
glucosylceramide in
cells of the body,
classically in the
tissue macrophages.
There are three broad
phenotypes recognized.
There is type one which does not
involve early onset
neurodegenerative disease,
although these
individuals can develop
Parkinson's disease
at an older age.
But the focus of
our presentation
is type 3 Gaucher disease,
the chronic neuronopathic
variety where
the onset of neurodegenerative
disease is in childhood.
It is associated with
severe visceral and
hematologic manifestations
that we reviewed in
our previous talk.
