Journal of Clinical Medicine,
Journal Year:
2024,
Volume and Issue:
13(23), P. 7195 - 7195
Published: Nov. 27, 2024
Anderson–Fabry
disease
(AFD)
remains
a
therapeutic
challenge
despite
advances
in
early
diagnosis
and
the
availability
of
enzyme
replacement
therapies
(ERTs).
While
initiation
therapy
can
mitigate
progression,
resistance
mechanisms—such
as
development
anti-drug
antibodies—limit
efficacy
current
treatments,
particularly
patients
with
severe
genetic
variants.
Chaperone
provides
targeted
option
for
subset
patients,
yet
significant
gaps
remain
treating
those
complete
deficiency.
This
perspective
article
explores
existing
landscape
reflects
on
emerging
such
mRNA
gene
therapies,
which
hold
promise
overcoming
mechanisms.
By
addressing
limitations
pharmacological
options
considering
future
innovations,
this
aims
to
outline
path
forward
more
effective
personalized
treatment
strategies
disease.
Cells,
Journal Year:
2024,
Volume and Issue:
13(14), P. 1190 - 1190
Published: July 13, 2024
Genetic
or
hereditary
kidney
disease
stands
as
a
pivotal
cause
of
chronic
(CKD).
The
proliferation
and
widespread
utilization
DNA
testing
in
clinical
settings
have
notably
eased
the
diagnosis
genetic
diseases,
which
were
once
elusive
but
are
now
increasingly
identified
cases
previously
deemed
CKD
unknown
etiology.
However,
despite
these
diagnostic
strides,
research
into
pathogenesis
novel
drug
development
faces
significant
hurdles,
chiefly
due
to
dearth
appropriate
animal
models
challenges
posed
by
limited
patient
cohorts
studies.
Conversely,
advent
human-induced
pluripotent
stem
cells
(hiPSCs)
offer
promising
avenue
for
research.
Particularly,
hiPSC-derived
organoid
systems
presents
platform
investigating
various
forms
diseases.
Moreover,
integration
CRISPR/Cas9
technique
this
system
holds
immense
potential
efficient
on
This
review
aims
explore
applications
vitro
organoids
generated
from
hiPSCs
study
diverse
Additionally,
it
will
delve
limitations
outline
future
perspectives
advancing
crucial
area.
Journal of Translational Medicine,
Journal Year:
2024,
Volume and Issue:
22(1)
Published: Oct. 24, 2024
Abstract
Fabry
disease
is
a
multi-organ
disease,
caused
by
mutations
in
the
GLA
gene
and
leading
to
progressive
accumulation
of
glycosphingolipids
due
enzymatic
absence
or
malfunction
encoded
alpha-galactosidase
A.
Since
pathomechanisms
are
not
yet
fully
understood
available
treatments
efficient
for
all
mutation
types
tissues,
further
research
highly
needed.
This
involves
many
different
model
types,
with
significant
effort
towards
establishment
an
vivo
model.
However,
these
models
did
replicate
variety
symptoms
observed
patients.
As
alternative
strategy,
patient-derived
somatic
cells
as
well
patient-independent
cell
lines
were
used
specific
aspects
vitro.
patients
present
phenotypes
according
level
residual
enzyme
activity,
pointing
necessity
personalized
modeling.
With
advent
induced
pluripotent
stem
cells,
derivation
multitude
disease-affected
became
possible,
even
patient-specific
mutation-specific
manner.
Only
recently,
three-dimensional
established
that
more
closely
resemble
native
tissue
investigated
organs
will
bring
closer
situation.
review
provides
overview
human
vitro
their
achievements
unravelling
pathomechanism
elucidating
current
future
treatment
strategies.
Pharmaceutics,
Journal Year:
2025,
Volume and Issue:
17(1), P. 104 - 104
Published: Jan. 14, 2025
Monogenic
disorders
are
a
group
of
human
diseases
caused
by
mutations
in
single
genes.
While
some
disease-altering
treatments
offer
relief
and
slow
the
progression
certain
conditions,
majority
monogenic
still
lack
effective
therapies.
In
recent
years,
gene
therapy
has
appeared
as
promising
approach
for
addressing
genetic
disorders.
However,
despite
advancements
manipulation
tools
delivery
systems,
several
challenges
remain
unresolved,
including
inefficient
delivery,
sustained
expression,
immunogenicity,
toxicity,
capacity
limitations,
genomic
integration
risks,
limited
tissue
specificity.
This
review
provides
an
overview
plasmid-based
techniques
methods
currently
employed
diseases,
highlighting
they
face
exploring
potential
strategies
to
overcome
these
barriers.
Biomedicines,
Journal Year:
2025,
Volume and Issue:
13(3), P. 624 - 624
Published: March 4, 2025
Fabry
disease
(FD)
is
an
X-linked
lysosomal
storage
disorder
characterized
by
deficiency
of
α-galactosidase
A
(α-GalA),
leading
to
the
accumulation
glycosphingolipids
and
multi-organ
dysfunction,
particularly
affecting
cardiovascular
renal
systems.
Disease-modifying
treatments
such
as
enzyme
replacement
therapy
(ERT)
oral
chaperone
(OCT)
have
limited
efficacy,
in
advanced
disease,
prompting
a
need
for
innovative
therapeutic
approaches
targeting
underlying
molecular
mechanisms
beyond
glycosphingolipid
alone.
Recent
insights
into
pathophysiology
FD
highlights
chronic
inflammation
mitochondrial,
lysosomal,
endothelial
dysfunction
key
mediators
progression.
Adjunctive
therapies
sodium-glucose
cotransporter-2
(SGLT2)
inhibitors,
glucagon-like
peptide-1
(GLP-1)
agonists,
mineralocorticoid
receptor
antagonists
(MRAs)
demonstrate
significant
benefits
conditions
including
heart
failure
kidney
disease.
These
drugs
also
modulate
pathways
involved
FD,
autophagy,
oxidative
stress,
pro-inflammatory
cytokine
signaling.
While
theoretical
foundations
support
their
utility,
dedicated
trials
are
necessary
confirm
efficacy
FD-specific
population.
This
narrative
review
importance
expanding
strategies
advocating
multi-faceted
approach
involving
evidence-based
adjunctive
improve
outcomes.
Tailored
research
focusing
on
diverse
phenotypes,
females
non-classical
variants
will
be
critical
advancing
care
improving
outcomes
this
complex
disorder.
hLife,
Journal Year:
2024,
Volume and Issue:
unknown
Published: May 1, 2024
Organoids
are
in
vitro
microstructures
similar
to
the
source
tissue
formed
by
self-organizing
construction
of
stem
cells
from
various
sources.
It
is
now
widely
recognized
as
a
powerful
model
facilitate
cancer
research
and
personalized
precision
therapy.
Since
successful
establishment
first
organoid
2009,
there
has
been
global
upsurge
research.
At
present,
organoids
have
used
on
mechanism
occurrence
development,
study
cell
interactions
tumor
microenvironment,
development
screening
new
drugs,
individualized
treatment
cancer.
In
addition,
chip
technology
biobanks
expected
further
promote
irreplaceable
role
medical
treatment.
this
review,
we
offer
comprehensive
outline
historical
their
advantages,
focusing
latest
progress
application
We
also
discuss
problems
that
need
be
solved
potential
applications
organoids.
This
review
summarizes
impact
treatment,
provide
view
BioDrugs,
Journal Year:
2024,
Volume and Issue:
38(5), P. 657 - 680
Published: Aug. 23, 2024
Genetic
substrate
reduction
therapy
(gSRT),
which
involves
the
use
of
nucleic
acids
to
downregulate
genes
involved
in
biosynthesis
storage
substances,
has
been
investigated
treatment
lysosomal
diseases
(LSDs).
Cells,
Journal Year:
2023,
Volume and Issue:
12(18), P. 2319 - 2319
Published: Sept. 20, 2023
Karyomegalic
interstitial
nephritis
(KIN)
is
a
genetic
kidney
disease
caused
by
mutations
in
the
FANCD2/FANCI-Associated
Nuclease
1
(FAN1)
gene
on
15q13.3,
which
results
karyomegaly
and
fibrosis
of
cells
through
incomplete
repair
DNA
damage.
The
aim
this
study
was
to
explore
possibility
using
human
induced
pluripotent
stem
cell
(hiPSC)-derived
organoid
system
for
modeling
FAN1-deficient
disease,
also
known
as
KIN.
We
generated
organoids
WTC-11
(wild-type)
hiPSCs
FAN1-mutant
include
KIN
patient-derived
FAN1-edited
(WTC-11
FAN1+/-),
created
CRISPR/Cas9
WTC-11-hiPSCs.
Kidney
from
each
group
were
treated
with
20
nM
mitomycin
C
(MMC)
24
or
48
h,
expression
levels
Ki67
H2A
histone
family
member
X
(H2A.X)
analyzed
detect
damage
assess
viability
within
organoids.
Both
WTC-11-hiPSCs
successfully
differentiated
into
without
structural
deformities.
MMC
treatment
h
significantly
increased
markers,
while
both
decreased.
However,
these
findings
observed
WTC-11-kidney
These
suggest
that
can
recapitulate
phenotype
disease.
