Biomedicines,
Год журнала:
2024,
Номер
12(9), С. 1992 - 1992
Опубликована: Сен. 2, 2024
An
increase
in
total
drug
(small
molecules
and
biologics)
approvals
by
the
Food
Drug
Administration
(FDA)
was
seen
2023
compared
with
previous
year.
Cancer
remained
disease
most
targeted
monoclonal
antibodies
(mAbs),
followed
autoimmune
conditions.
Our
data
reveal
prevalence
of
for
biologics
even
during
years
when
number
authorizations
low,
such
as
2022.
Over
half
drugs
that
received
green
light
benefited
from
expedited
programs,
incidence
many
diseases
increased.
In
addition,
over
approved
Orphan
Designation
FDA.
This
narrative
review
delves
into
details
significant
2023,
including
mAbs,
enzymes,
proteins,
explaining
their
mechanisms
action,
differences
drugs,
placebo,
standards
care,
outcomes
clinical
trials.
Given
varying
authorized
annually
U.S.
health
authority,
this
also
examines
limits
external
influences
FDA′s
decisions
independence
regarding
withdrawals.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(7), С. 3995 - 3995
Опубликована: Апрель 3, 2024
Neurodegenerative
disorders
(NDs)
have
become
increasingly
common
during
the
past
three
decades.
Approximately
15%
of
total
population
world
is
affected
by
some
form
NDs,
resulting
in
physical
and
cognitive
disability.
The
most
NDs
include
Alzheimer’s
disease,
Parkinson’s
amyotrophic
lateral
sclerosis,
Huntington’s
disease.
Although
are
caused
a
complex
interaction
genetic,
environmental,
lifestyle
variables,
neuroinflammation
known
to
be
associated
with
all
often
leading
permanent
damage
neurons
central
nervous
system.
Furthermore,
numerous
emerging
pieces
evidence
demonstrated
that
inflammation
not
only
supports
progression
but
can
also
serve
as
an
initiator.
Hence,
various
medicines
capable
preventing
or
reducing
been
investigated
ND
treatments.
While
anti-inflammatory
medicine
has
shown
promising
benefits
several
preclinical
models,
clinical
outcomes
questionable.
In
this
review,
we
discuss
their
current
treatment
strategies,
role
pathophysiology
use
agents
potential
therapeutic
option.
Progress in Retinal and Eye Research,
Год журнала:
2024,
Номер
101, С. 101273 - 101273
Опубликована: Май 15, 2024
The
retina
is
an
emerging
CNS
target
for
potential
noninvasive
diagnosis
and
tracking
of
Alzheimer's
disease
(AD).
Studies
have
identified
the
pathological
hallmarks
AD,
including
amyloid
β-protein
(Aβ)
deposits
abnormal
tau
protein
isoforms,
in
retinas
AD
patients
animal
models.
Moreover,
structural
functional
vascular
abnormalities
such
as
reduced
blood
flow,
Aβ
deposition,
blood-retinal
barrier
damage,
along
with
inflammation
neurodegeneration,
been
described
mild
cognitive
impairment
dementia.
Histological,
biochemical,
clinical
studies
demonstrated
that
nature
severity
pathologies
brain
correspond.
Proteomics
analysis
revealed
a
similar
pattern
dysregulated
proteins
biological
pathways
patients,
enhanced
inflammatory
neurodegenerative
processes,
impaired
oxidative-phosphorylation,
mitochondrial
dysfunction.
Notably,
investigational
imaging
technologies
can
now
detect
AD-specific
deposits,
well
vasculopathy
neurodegeneration
living
suggesting
alterations
at
different
stages
links
to
pathology.
Current
exploratory
ophthalmic
modalities,
optical
coherence
tomography
(OCT),
OCT-angiography,
confocal
scanning
laser
ophthalmoscopy,
hyperspectral
imaging,
may
offer
promise
assessment
AD.
However,
further
research
needed
deepen
our
understanding
AD's
impact
on
its
progression.
To
advance
this
field,
future
require
replication
larger
diverse
cohorts
confirmed
biomarkers
standardized
retinal
techniques.
This
will
validate
aiding
early
screening
monitoring.
Cells,
Год журнала:
2024,
Номер
13(8), С. 719 - 719
Опубликована: Апрель 21, 2024
Alzheimer’s
disease
(AD)
is
a
devastating
neurodegenerative
disorder
characterized
by
progressive
cognitive
decline
and
memory
loss,
imposing
significant
burden
on
affected
individuals
their
families.
Despite
the
recent
promising
progress
in
therapeutic
approaches,
more
needs
to
be
done
understand
intricate
molecular
mechanisms
underlying
development
progression
of
AD.
Growing
evidence
points
epigenetic
changes
as
playing
pivotal
role
pathogenesis
disease.
The
dynamic
interplay
between
genetic
environmental
factors
influences
landscape
AD,
altering
gene
expression
patterns
associated
with
key
pathological
events
pathogenesis.
To
this
end,
alterations
not
only
impact
genes
implicated
AD
but
also
contribute
dysregulation
crucial
cellular
processes,
including
synaptic
plasticity,
neuroinflammation,
oxidative
stress.
Understanding
complex
provides
new
avenues
for
interventions.
This
review
comprehensively
examines
DNA
methylation
histone
modifications
context
It
aims
deeper
understanding
facilitate
targeted
strategies.
International Journal of Molecular Sciences,
Год журнала:
2024,
Номер
25(9), С. 4969 - 4969
Опубликована: Май 2, 2024
Tau
protein
misfolding
and
aggregation
are
pathological
hallmarks
of
Alzheimer's
disease
over
twenty
neurodegenerative
disorders.
However,
the
molecular
mechanisms
tau
in
vivo
remain
incompletely
understood.
There
two
types
aggregates
brain:
soluble
(oligomers
protofibrils)
insoluble
filaments
(fibrils).
Compared
to
filamentous
aggregates,
more
toxic
exhibit
prion-like
transmission,
providing
seeds
for
templated
misfolding.
Curiously,
its
native
state,
is
a
highly
soluble,
heat-stable
that
does
not
form
fibrils
by
itself,
even
when
hyperphosphorylated.
In
vitro
studies
have
found
negatively
charged
molecules
such
as
heparin,
RNA,
or
arachidonic
acid
generally
required
induce
aggregation.
Two
recent
breakthroughs
provided
new
insights
into
mechanisms.
First,
an
intrinsically
disordered
protein,
undergo
liquid-liquid
phase
separation
(LLPS)
both
inside
cells.
Second,
cryo-electron
microscopy
has
revealed
diverse
fibrillar
conformations
associated
with
different
Nonetheless,
only
core
structurally
resolved,
remainder
appears
"fuzzy
coat".
From
this
review,
it
further
(1)
clarify
role
LLPS
aggregation;
(2)
unveil
structural
features
aggregates;
(3)
understand
involvement
fuzzy
coat
regions
oligomer
fibril
formation.
CNS Drugs,
Год журнала:
2024,
Номер
38(8), С. 613 - 624
Опубликована: Июнь 27, 2024
Alzheimer's
disease
(AD)
is
a
complex
multifaceted
disease.
Recently
approved
anti-amyloid
monoclonal
antibodies
slow
progression
by
approximately
30%,
and
combination
therapy
appears
necessary
to
prevent
the
onset
of
AD
or
produce
greater
slowing
cognitive
functional
decline.
Combination
therapies
may
address
core
features,
non-specific
co-pathology
commonly
occurring
in
patients
with
(e.g.,
inflammation),
non-AD
pathologies
that
co-occur
α-synuclein).
be
advanced
through
co-development
more
than
one
new
molecular
entity
add-on
strategies
including
an
agent
plus
entity.
Addressing
currently
urgent
since
on
included
clinical
trials
for
experimental
agents.
Phase
1
information
must
generated
each
drug
development.
2
3
contrast
entity,
as
standard
care,
combination.
More
development
programs
modified
combinatorial
designs
are
required
two
entities.
Biomarkers
markedly
affected
antibodies,
these
effects
anticipated
trials.
Examining
target
engagement
biomarkers
comparing
magnitude
sequence
biomarker
changes
those
receiving
therapy,
compared
monotherapy,
informative.
Using
network-based
medicine
approaches,
computational
identify
rational
combinations
using
effect
network
mapping.
JAMA Neurology,
Год журнала:
2024,
Номер
81(6), С. 645 - 645
Опубликована: Апрель 1, 2024
Importance
Neuropsychiatric
syndromes
(NPSs)
are
common
in
neurodegenerative
disorders
(NDDs);
compromise
the
quality
of
life
patients
and
their
care
partners;
associated
with
faster
disease
progression,
earlier
need
for
nursing
home
care,
poorer
life.
Advances
translational
pharmacology,
clinical
trial
design
conduct,
understanding
pathobiology
NDDs
bringing
new
therapies
to
care.
Observations
Consensus
definitions
have
evolved
psychosis,
agitation,
apathy,
depression,
disinhibition
NDDs.
Psychosocial
interventions
may
reduce
mild
behavioral
symptoms
NDD,
pharmacotherapy
is
available
NPSs
Brexpiprazole
approved
treatment
agitation
Alzheimer
dementia,
pimavanserin
delusions
hallucinations
psychosis
Parkinson
disease.
Trials
being
conducted
across
several
NDDs,
a
variety
mechanisms
action
assessed
effect
on
NPSs.
Conclusions
Relevance
Detection
characterization
foundation
excellent
New
inform
choices
regarding
populations
translate
into
practice.
pharmacologic
improve
caregivers.
Approved
agents
establish
regulatory
precedents,
demonstrate
successful
strategies,
provide
further
advances
development.
Antibody Therapeutics,
Год журнала:
2024,
Номер
7(2), С. 132 - 156
Опубликована: Март 15, 2024
In
calendar
year
2023,
the
United
States
Food
and
Drug
Administration
(US
FDA)
approved
a
total
of
55
new
molecular
entities,
which
12
were
in
class
therapeutic
antibodies.
Besides
antibody
protein
drugs,
US
FDA
also
another
five
non-antibody
making
broader
drugs
about
31%
drugs.
Among
antibodies
by
FDA,
8
relatively
standard
IgG
formats,
3
bivalent,
bispecific
1
was
trivalent,
antibody.
no
antibody-drug
conjugates,
immunocytokines
or
chimeric
antigen
receptor-T
cells
approved.
Of
antibodies,
two
targeted
programmed
cell
death
receptor-1
(PD-1)
for
orphan
indications,
CD20
diffuse
large
B
lymphoma,
different
receptors
(B-cell
maturation
[BCMA]
G-coupled
receptor
C,
group
5,
member
D
[GPRC5D])
treatment
multiple
myeloma,
one
each
that
amyloid-β
protofibrils
Alzheimer's
disease,
neonatal
Fc
alpha-chain
myasthenia
gravis,
complement
factor
C5
CD55
deficiency
with
hyper-activation
complement,
angiopathic
thrombosis
severe
protein-losing
enteropathy
interleukin
(IL)-23p19
severely
active
ulcerative
colitis,
IL-17A-F
plaque
psoriasis
respiratory
syncytial
virus
(RSV)-F
season-long
RSV
prophylaxis
infants.
Alzheimer s Research & Therapy,
Год журнала:
2024,
Номер
16(1)
Опубликована: Май 21, 2024
Abstract
Alzheimer’s
disease
(AD)
poses
a
significant
public
health
problem,
affecting
millions
of
people
across
the
world.
Despite
decades
research
into
therapeutic
strategies
for
AD,
effective
prevention
or
treatment
this
devastating
disorder
remains
elusive.
In
review,
we
discuss
potential
photobiomodulation
(PBM)
preventing
and
alleviating
AD-associated
pathologies,
with
focus
on
biological
mechanisms
underlying
therapy.
Future
directions
guidance
clinical
practice
non-invasive
non-pharmacological
therapy
are
also
highlighted.
The
available
evidence
indicates
that
different
paradigms,
including
transcranial
systemic
PBM,
along
recently
proposed
remote
all
could
be
promising
AD.
PBM
exerts
diverse
effects,
such
as
enhancing
mitochondrial
function,
mitigating
neuroinflammation
caused
by
activated
glial
cells,
increasing
cerebral
perfusion,
improving
glymphatic
drainage,
regulating
gut
microbiome,
boosting
myokine
production,
modulating
immune
system.
We
suggest
may
serve
powerful
intervention
