Rare Diseases Symptoms Automatic Extraction
Home
A random Abstract
Our Project
Our Team
A combined therapeutic approach for pyruvate dehydrogenase deficiency using self-complementary adeno-associated virus serotype-specific vectors and dichloroacetate.
[pyruvate dehydrogenase deficiency]
We
determined
the
ability
of
self-complementary
adeno-associated
virus
(
scAAV
)
vectors
to
deliver
and
express
the
pyruvate
dehydrogenase
E
1
alpha
subunit
gene
(
PDHA
1
)
in
primary
cultures
of
skin
fibroblasts
from
3
patients
with
defined
mutations
in
PHDA
1
and
3
healthy
subjects
.
Cells
were
transduced
with
scAAV
vectors
containing
the
cytomegalovirus
promoter-driven
enhanced
green
fluorescent
protein
(
EGFP
)
reporter
gene
at
a
vector
:
cell
ratio
of
200
.
Transgene
expression
was
measured
72
h
later
.
The
transduction
efficiency
of
scAAV
2
and
scAAV
6
vectors
was
3
-
to
5
-
fold
higher
than
that
of
the
other
serotypes
,
which
were
subsequently
used
to
transduce
fibroblasts
with
wild-
type
PDHA
1
cDNA
under
the
control
of
the
chicken
beta
-action
(
CBA
)
promoter
at
a
vector
:
cell
ratio
of
1000
.
Total
PDH
-
specific
activity
and
E
1
alpha
protein
expression
were
determined
10
days
post-transduction
.
Both
vectors
increased
E
1
alpha
expression
40
-
60
%
in
both
control
and
patient
cells
,
and
increased
PDH
activity
in
two
patient
cell
lines
.
We
also
used
dichloroacetate
(
DCA
)
to
maximally
activate
PDH
through
dephosphorylation
of
E
1
alpha
.
Exposure
for
24
h
to
5
mM
DCA
increased
PDH
activity
in
non-transduced
control
(
mean
37
%
increase
)
and
PDH
deficient
(
mean
44
%
increase
)
cells
.
Exposure
of
transduced
patient
fibroblasts
to
DCA
increased
PDH
activity
up
to
90
%
of
the
activity
measured
in
untreated
control
cells
.
DCA
also
increased
expression
of
E
1
alpha
protein
and
,
to
variable
extents
,
that
of
other
components
of
the
PDH
complex
in
both
non-transduced
and
transduced
cells
.
These
data
suggest
that
a
combined
gene
delivery
and
pharmacological
approach
may
hold
promise
for
the
treatment
of
PDH
deficiency
.
Diseases
Validation
Diseases presenting
"skin fibroblasts"
symptom
child syndrome
cowden syndrome
cystinuria
dentinogenesis imperfecta
dystrophic epidermolysis bullosa
epidermolysis bullosa simplex
gm1 gangliosidosis
homocystinuria without methylmalonic aciduria
krabbe disease
malignant atrophic papulosis
monosomy 21
neonatal adrenoleukodystrophy
pyruvate dehydrogenase deficiency
werner syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
You can validate or delete this automatically detected symptom
Validate the Symptom
Delete the Symptom