Neurotherapeutics,
Год журнала:
2024,
Номер
21(4), С. e00434 - e00434
Опубликована: Июль 1, 2024
Viral
vector
mediated
gene
therapies
for
neurodegenerative
and
neurodevelopmental
conditions
that
require
neurosurgical
administration
continue
to
expand.
We
systematically
reviewed
the
National
Institutes
of
Health
(NIH)
ClinicalTrials.gov
database
identify
all
clinical
trials
studying
in-vivo
viral
targeted
CNS
diseases.
isolated
studies
which
delivered
using
approaches:
intracisternal,
intraventricular,
and/or
intraparenchymal.
Clinical
primarily
registered
in
international
countries
were
included
if
they
referenced
by
an
NIH
trial.
performed
a
scoping
review
preclinical
supported
each
human
Key
data
aggregated
characterize
capsid
design,
delivery
methods,
expression
profile,
benefit.
A
total
64
identified
active,
completed,
terminated,
long-term
follow-up
stages.
range
across
pediatric
adult
populations
are
being
studied
with
therapy,
including
Alzheimer's
disease,
Parkinson's
AADC
deficiency,
sphingolipidoses,
mucopolysaccharidoses,
neuronal
ceroid
lipofuscinoses,
spinal
muscular
atrophy,
adrenoleukodystrophy,
Canavan
frontotemporal
dementia,
Huntington's
Rett
syndrome,
Dravet
mesial
temporal
lobe
epilepsy,
glutaric
acidemia.
Adeno-associated
vectors
(AAVs)
utilized
majority
tested
therapies,
serotypes,
regulatory
elements,
monitoring
varying
based
on
disease
studied.
Intraparenchymal
has
evolved
significantly,
MRI-guided
convection-enhanced
established
as
gold
standard
method
pioneering
novel
targets.
NeuroImage,
Год журнала:
2021,
Номер
235, С. 118017 - 118017
Опубликована: Март 29, 2021
Brain
perturbation
studies
allow
detailed
causal
inferences
of
behavioral
and
neural
processes.
Because
the
combination
brain
methods
measurement
techniques
is
inherently
challenging,
research
in
humans
has
predominantly
focused
on
non-invasive,
indirect
perturbations,
or
neurological
lesion
studies.
Non-human
primates
have
been
indispensable
as
a
neurobiological
system
that
highly
similar
to
while
simultaneously
being
more
experimentally
tractable,
allowing
visualization
functional
structural
impact
systematic
perturbation.
This
review
considers
state
art
non-human
primate
with
focus
approaches
can
be
combined
neuroimaging.
We
consider
both
non-reversible
(lesions)
reversible
temporary
perturbations
such
electrical,
pharmacological,
optical,
optogenetic,
chemogenetic,
pathway-selective,
ultrasound
based
interference
methods.
Method-specific
considerations
from
development
community
are
offered
facilitate
this
field
support
further
innovations.
conclude
by
identifying
novel
avenues
for
innovation
highlighting
clinical
translational
potential
Neuron,
Год журнала:
2023,
Номер
111(14), С. 2258 - 2273.e10
Опубликована: Май 16, 2023
The
prefrontal
cortex
(PFC)
has
dramatically
expanded
in
primates,
but
its
organization
and
interactions
with
other
brain
regions
are
only
partially
understood.
We
performed
high-resolution
connectomic
mapping
of
the
marmoset
PFC
found
two
contrasting
corticocortical
corticostriatal
projection
patterns:
"patchy"
projections
that
formed
many
columns
submillimeter
scale
nearby
distant
"diffuse"
spread
widely
across
striatum.
Parcellation-free
analyses
revealed
representations
gradients
these
projections'
local
global
distribution
patterns.
also
demonstrated
column-scale
precision
reciprocal
connectivity,
suggesting
contains
a
mosaic
discrete
columns.
Diffuse
showed
considerable
diversity
laminar
patterns
axonal
spread.
Altogether,
fine-grained
reveal
important
principles
long-distance
circuits
marmosets
provide
insights
into
functional
primate
brain.
The Innovation,
Год журнала:
2023,
Номер
5(1), С. 100548 - 100548
Опубликована: Ноя. 27, 2023
•Micro/nanosystems
show
their
potential
to
address
the
challenges
of
precise
drug
delivery
brain.•Microfluidic
platforms
enable
creation
biomimetic
in
vitro
brain
models.•Micro/nano
materials
is
emerging
as
a
key
player
controllable
delivery.•The
minimally
invasive
fiberbot
microsystem
reduces
procedure's
invasiveness.•Image
tracking
micro/nanosystems
allows
for
controlled
therapeutic
interventions.
Drug
crucial
treatment
central
nervous
system
disorders.
While
significant
progress
has
been
made
recent
years,
there
are
still
major
achieving
brain.
Unmet
clinical
needs
arise
from
various
factors,
including
transport,
handling
large
doses,
methods
crossing
biological
barriers,
use
imaging
guidance,
and
effective
models
analyzing
delivery.
Recent
advances
have
shown
promise
addressing
some
these
challenges.
These
include
utilization
microfluidic
test
validate
process
setting,
development
novel
micro/nanocarriers
loads
across
blood-brain
barrier,
implementation
micro-intervention
systems
delivering
drugs
through
intraparenchymal
or
peripheral
routes.
In
this
article,
we
present
review
latest
developments
We
also
delve
into
relevant
diseases,
conventional
methods.
addition,
discuss
future
prospects
robotic
equipped
with
directed
transportation,
real-time
image
closed-loop
control.
Glioblastomas
are
invasive
brain
tumors
with
high
therapeutic
resistance.
Neuron-to-glioma
synapses
have
been
shown
to
promote
glioblastoma
progression.
However,
a
characterization
of
tumor-connected
neurons
has
hampered
by
lack
technologies.
Here,
we
adapted
retrograde
tracing
using
rabies
viruses
investigate
and
manipulate
neuron-tumor
networks.
Glioblastoma
rapidly
integrated
into
neural
circuits
across
the
brain,
engaging
in
widespread
functional
communication,
cholinergic
driving
invasion.
We
uncovered
patient-specific
tumor-cell-state-dependent
differences
synaptogenic
gene
expression
associated
connectivity
subsequent
invasiveness.
Importantly,
radiotherapy
enhanced
increased
neuronal
activity.
In
turn,
simultaneous
activity
inhibition
showed
effects,
indicative
role
for
neuron-to-glioma
contributing
Lastly,
rabies-mediated
genetic
ablation
halted
progression,
offering
viral
strategy
tackle
glioblastoma.
Together,
this
study
provides
framework
comprehensively
characterize
networks
target
Molecular Biomedicine,
Год журнала:
2024,
Номер
5(1)
Опубликована: Авг. 29, 2024
Herpes
simplex
virus
(HSV),
an
epidemic
human
pathogen
threatening
global
public
health,
gains
notoriety
for
its
complex
pathogenesis
that
encompasses
lytic
infection
of
mucosal
cells,
latent
within
neurons,
and
periodic
reactivation.
This
intricate
interplay,
coupled
with
HSV's
sophisticated
immune
evasion
strategies,
gives
rise
to
various
diseases,
including
genital
lesions,
neonatal
encephalitis,
cancer.
Despite
more
than
70
years
relentless
research,
effective
preventive
or
therapeutic
vaccine
against
HSV
has
yet
emerge,
primarily
due
the
limited
understanding
virus-host
interactions,
which
in
turn
impedes
identification
targets.
However,
unique
pathological
features,
substantial
genetic
load
capacity,
high
replicability,
transmissibility,
neurotropism,
render
it
a
promising
candidate
applications,
spanning
oncolytic
virotherapy,
gene
therapies,
even
as
imaging
tracer
neuroscience.
In
this
review,
we
comprehensively
update
recent
breakthroughs
evasion,
critically
summarize
progress
made
development,
discuss
multifaceted
applications
biological
tool.
Importantly,
highlight
both
success
challenges,
emphasizing
critical
need
intensified
research
into
HSV,
aim
providing
deeper
insights
can
not
only
advance
treatment
strategies
but
also
broaden
application
horizons.
