Tofersen for SOD1 amyotrophic lateral sclerosis: a systematic review and meta-analysis
Neurological Sciences,
Год журнала:
2025,
Номер
unknown
Опубликована: Янв. 17, 2025
Abstract
Objective
Tofersen,
an
antisense
oligonucleotide,
has
recently
received
FDA
and
EMA
approval
for
treating
amyotrophic
lateral
sclerosis
(ALS)
in
adults
with
SOD1
gene
mutations.
This
systematic
review
meta-analysis
synthesized
evidence
on
tofersen’s
safety
efficacy
patients
-related
ALS.
Methods
A
comprehensive
search
of
three
databases
was
conducted
from
inception
through
October
2024.
Eligible
studies
included
clinical
trials,
observational
studies,
case
studies.
Meta-analyses
were
using
a
random-effects
model
RevMan.
Results
Twelve
involving
195
treated
tofersen
met
the
inclusion
criteria,
comprising
two
randomized
controlled
trials
(RCTs),
five
cohort
one
series,
four
reports.
Tofersen
demonstrated
promising
effects,
notably
reducing
levels
cerebrospinal
fluid
neurofilament
light
chain
(NfL)
plasma,
biomarker
strongly
correlated
ALS
progression
survival.
Meta-analysis
RCTs
showed
significantly
lower
rate
decline
Functional
Rating
Scale-Revised
(ALSFRS-R)
scores
baseline
group
compared
to
placebo
(SMD
=
0.44,
95%
CI
[0.05
0.83],
P
0.03)
significant
reduction
predicted
Slow
Vital
Capacity
(
0.005).
In
pre-post
decrease
(ALSFRS-R
rate)
observed
(MD
-0.28,
[-0.40
-0.15],
<
0.0001).
Reported
adverse
events
consistent
or
procedural
effects.
Conclusion
Current
suggests
that
effectively
reduces
NfL
slow
disease
ALS,
showing
promise
as
targeted
therapeutic
option.
Язык: Английский
Barriers in the Nervous System: Challenges and Opportunities for Novel Biomarkers in Amyotrophic Lateral Sclerosis
Cells,
Год журнала:
2025,
Номер
14(11), С. 848 - 848
Опубликована: Июнь 5, 2025
Amyotrophic
Lateral
Sclerosis
(ALS)
is
a
complex
neurodegenerative
disorder
characterized
by
wide
phenotypic
heterogeneity.
Despite
efforts
to
carefully
define
and
stratify
ALS
patients
according
their
clinical
genetic
features,
prognosis
prediction
still
remains
unreliable.
Biomarkers
that
reflect
changes
in
the
central
nervous
system
would
be
useful,
but
physical
impossibility
of
direct
sampling
analysis
makes
them
challenging
validate.
A
highly
explored
option
identification
neuronal-specific
markers
could
analyzed
peripheral
biofluids.
This
review
focuses
on
description
biological
barriers
composition
biofluids
which
disease
biomarkers
are
actively
searched.
Finally,
we
comment
already
validated
biomarkers,
such
as
neurofilament
light
chain,
show
potential
extracellular
vesicles
(EVs)
cell-free
DNA
additional
for
prediction.
Язык: Английский