Rare Diseases Symptoms Automatic Extraction
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A random Abstract
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Identification of hematopoietic stem cell-specific miRNAs enables gene therapy of globoid cell leukodystrophy.
[krabbe disease]
Globoid
cell
leukodystrophy
(
GLD
;
also
known
as
Krabbe
disease
)
is
an
invariably
fatal
lysosomal
storage
disorder
caused
by
mutations
in
the
galactocerebrosidase
(
GALC
)
gene
.
Hematopoietic
stem
cell
(
HSC
)
-
based
gene
therapy
is
being
explored
for
GLD
;
however
,
we
found
that
forced
GALC
expression
was
toxic
to
HSCs
and
early
progenitors
,
highlighting
the
need
for
improved
regulation
of
vector
expression
.
We
used
a
genetic
reporter
strategy
based
on
lentiviral
vectors
to
detect
microRNA
activity
in
hematopoietic
cells
at
single
-cell
resolution
.
We
report
that
miR-
126
and
miR-
130
a
were
expressed
in
HSCs
and
early
progenitors
from
both
mice
and
humans
,
but
not
in
differentiated
progeny
.
Moreover
,
repopulating
HSCs
could
be
purified
solely
on
the
basis
of
miRNA
expression
,
providing
a
new
method
relevant
for
human
HSC
isolation
.
By
incorporating
miR-
126
target
sequences
into
a
GALC
-expressing
vector
,
we
suppressed
GALC
expression
in
HSCs
while
maintaining
robust
expression
in
mature
hematopoietic
cells
.
This
approach
protected
HSCs
from
GALC
toxicity
and
allowed
successful
treatment
of
a
mouse
GLD
model
,
providing
a
rationale
to
explore
HSC-based
gene
therapy
for
GLD
.
Diseases
Validation
Diseases presenting
"leukodystrophy"
symptom
achondroplasia
adrenomyeloneuropathy
alexander disease
cadasil
canavan disease
carcinoma of the gallbladder
classical phenylketonuria
coats disease
fabry disease
gm1 gangliosidosis
krabbe disease
neonatal adrenoleukodystrophy
phenylketonuria
pyruvate dehydrogenase deficiency
wiskott-aldrich syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
This symptom has already been validated