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Hematopoietic stem cell transplantation and hematopoietic stem cell gene therapy in X-linked adrenoleukodystrophy.
[adrenomyeloneuropathy]
Allogeneic
hematopoietic
stem
cell
transplantation
(
HSCT
)
is
the
only
therapeutic
approach
that
can
arrest
cerebral
demyelination
of
X-
linked
adrenoleukodystrophy
(
ALD
)
in
boys
and
results
in
long
-term
in
a
good
quality
of
life
,
provided
the
procedure
is
performed
at
an
early
stage
of
disease
.
Similar
benefits
of
allogeneic
HSCT
have
been
demonstrated
in
adults
with
cerebral
ALD
.
However
,
it
is
not
yet
known
whether
allogeneic
HSCT
can
prevent
or
rescue
adrenomyeloneuropathy
.
Allogeneic
HSCT
remains
associated
with
significant
morbidity
and
mortality
risks
,
particularly
in
adults
,
and
not
all
ALD
patients
have
donors
despite
the
availability
of
cord
blood
.
The
absence
of
biological
markers
that
can
predict
the
evolutivity
of
cerebral
disease
is
a
major
limitation
to
propose
in
due
time
allogeneic
HSCT
to
ALD
patients
.
Recently
,
HSC
gene
therapy
using
lentiviral
vector
was
shown
to
have
comparable
efficacy
than
allogeneic
HSCT
in
two
boys
with
cerebral
ALD
who
had
no
Human-leukocyte-antigen
(
HLA
)
-
matched
donor
.
If
these
results
are
confirmed
in
an
extended
series
of
patients
,
HSC
gene
therapy
may
become
the
first
therapeutic
option
for
all
ALD
male
patients
who
develop
cerebral
demyelination
.
Diseases
Validation
Diseases presenting
"demyelination"
symptom
adrenomyeloneuropathy
alexander disease
canavan disease
classical phenylketonuria
homocystinuria without methylmalonic aciduria
kallmann syndrome
krabbe disease
locked-in syndrome
neonatal adrenoleukodystrophy
neuralgic amyotrophy
primary hyperoxaluria type 1
pyruvate dehydrogenase deficiency
sneddon syndrome
waldenström macroglobulinemia
wiskott-aldrich syndrome
x-linked adrenoleukodystrophy
zellweger syndrome
This symptom has already been validated