Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
Bone marrow transplantation increases efficacy of central nervous system-directed enzyme replacement therapy in the murine model of globoid cell leukodystrophy.
[krabbe disease]
Globoid
cell
leukodystrophy
(
GLD
,
Krabbe
disease
)
,
is
an
autosomal
recessive
,
neurodegenerative
disease
caused
by
the
deficiency
of
the
lysosomal
enzyme
galactocerebrosidase
(
GALC
)
.
In
the
absence
of
GALC
,
the
toxic
metabolite
psychosine
accumulates
in
the
brain
and
causes
the
death
of
the
myelin-producing
cells
,
oligodendrocytes
.
Currently
,
the
only
therapy
for
GLD
is
hematopoietic
stem
cell
transplantation
using
bone
marrow
(
BMT
)
or
umbilical
cord
blood
.
However
,
this
is
only
partially
effective
.
Previous
studies
have
shown
that
enzyme
replacement
therapy
(
ERT
)
provides
some
therapeutic
benefit
in
the
murine
model
of
GLD
,
the
Twitcher
mouse
.
Experiments
have
also
shown
that
two
disparate
therapies
can
produce
synergistic
effects
when
combined
.
The
current
study
tests
the
hypothesis
that
BMT
will
increase
the
therapeutic
effects
of
ERT
when
these
two
treatments
are
combined
.
Twitcher
mice
were
treated
with
either
ERT
alone
or
both
ERT
and
BMT
during
the
first
2
-
4
days
of
life
.
Recombinant
enzyme
was
delivered
by
intracerebroventricular
(
ICV
)
and
intrathecal
(
IT
)
injections
.
Twitcher
mice
receiving
ERT
had
supraphysiological
levels
of
GALC
activity
in
the
brain
24
h
after
injection
.
At
36
days
of
age
,
ERT-treated
Twitcher
mice
had
reduced
psychosine
levels
,
reduced
neuroinflammation
,
improved
motor
function
,
and
increased
lifespan
.
Twitcher
mice
receiving
both
ERT
and
BMT
had
significantly
increased
lifespan
,
improved
motor
function
,
reduced
psychosine
levels
,
and
reduced
neuroinflammation
in
certain
areas
of
the
brain
compared
to
untreated
or
ERT-treated
Twitcher
mice
.
Together
,
these
results
indicate
that
BMT
enhances
the
efficacy
of
ERT
in
GLD
.
Diseases
Validation
Diseases presenting
"improved motor function, and increased lifespan"
symptom
krabbe disease
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom