Could a nasal spray help delay Alzheimer’s onset in the future?
The number of people with
dementia is forecast to almost triple by 2050.
Around 70% of these cases are
likely to be Alzheimer’s disease, the most common form of dementia.
Current treatments can relieve
some of the symptoms, and new disease-modifying treatments are not widely
available.
Now, researchers have developed
a nasal spray that, in a mouse model, slows down inflammation and clears
protein buildup in Alzheimer’s disease.
The researchers suggest the
spray might delay Alzheimer’s progression by up to 15 years in people.
Population growth and aging
mean that the number of people with dementia is forecast to reach almost 152.8
millionTrusted Source by 2050.
There are several forms of
dementia, but the most common, Alzheimer’s disease, currently accounts for up
to 70%Trusted Source of cases.
Monoclonal antibody treatments,
such as lecanemab and donanemab, are the first disease-modifying therapies for
Alzheimer’s.
They clear the beta-amyloid
plaquesTrusted Source that are a characteristic of Alzheimer’s, potentially
delaying the cognitive symptoms. However, the treatments are expensive, and
some experts are concerned that the risk of side effects may outweigh their
benefits.
In a new study from Texas A
& M University College of Medicine, researchers have used a nasal spray to
target microglia and astrocytes — cells that cause neuroinflammation (brain
inflammation) — delaying the progression of Alzheimer’s disease in a mouse
model.
They suggest that, if similar
effects are confirmed in people, the spray could delay Alzheimer’s progression
by up to 15 years.
The research is published in
the Journal of Extracellular VesiclesTrusted Source.
Courtney Kloske, PhD,
Alzheimer’s Association director of scientific engagement, who was not involved
in this study, told Medical News Today that its findings are encouraging but
that much more research is needed to confirm them:
“Models are important in
helping us understand the basic biology of the disease, but we need human
studies in representative populations for ideas to be fully validated.
Microglia are an incredibly complex immune cell in the brain and researchers
are still working to understand why they respond the way they do at different
points in disease. Therefore, while these are intriguing findings, more
research is needed to understand the impacts and outcomes of this kind of
intervention on people living with, or at risk for, Alzheimer’s.”
Spray targets overactive immune
cells in the brain
Microglia and astrocytes play a
key role in neuroinflammation in Alzheimer’s disease. In healthy brains, they
protect nerve cells and remove damaged nerve tissue, but in Alzheimer’s, after
initially clearing beta-amyloid plaques, they become overactive and destroy
nerve cells.
Using a mouse model of the
early stages of Alzheimer’s disease, the researchers administered a nasal spray
containing an anti-inflammatory treatment derived from stem cells in
extracellular vesiclesTrusted Source.
The aim was to target these
immune cells to decrease inflammation and reduce the buildup of harmful
proteins in the brain.
They gave the 3-month old mice
— both mice genetically modified to display Alzheimer’s-like symptoms
(transgenic mice) and wild-type mice — 2 doses of the nasal spray containing
the treatment, or a placebo spray, 1 week apart.
Seventy-two hours after the
second dose, they euthanized five mice, to assess the numbers and activity of
microglia and astrocytes.
Three weeks after the second
treatment, they subjected the rest of the mice to a series of behavioral tests.
The researchers repeated these tests regularly over the next month to monitor
the mice’s cognitive function following treatment. They then euthanized the
mice and analyzed their brains.
Spray treatment leads to lower
inflammation, better cognitive function
In this mouse model, untreated
transgenic mice usually show characteristic signs of Alzheimer’s such as
beta-amyloid plaques, increased microglial activity, and inflammation by the
age of 4.5 months.
However, at 4.5 months old, the
mice that received the nasal spray treatment in this study had reduced
microglial clusters, as well as reduced activation of genes associated with
neuroinflammation. In addition, they had fewer beta-amyloid plaques than the
untreated mice.
These reduced inflammatory
effects were most notable in the hippocampus — the area of the brain that plays
a major role in learning and memory — which is severely affected by Alzheimer’s
disease.
In behavioral tests, both male
and female treated mice showed better cognitive and mood function than the
untreated mice.
However, Clifford Segil, DO, a
neurologist at Providence Saint John’s Health Center in Santa Monica, CA, who
was not involved in this research, emphasized that this was early days for
plaque-removing treatments.
“The authors in the study noted
nasal delivered stem cells could decrease the number of plaques in Alzheimer’s
dementia patients and there are medications being used around the world right
now doing the same thing. Post-marketing surveillance is going to determine if
these plaque reducing medicines cause any noticeable cognitive improvements,”
he told MNT.
“If the clinical use results in
patients with improved memory, unlike the trials which resulted in these
medications’ approval, novel and early methods to decrease brain plaques will
be extremely desirable,” Segil added.
Brain immune cell regulation
clears toxic plaques, but are there side effects?
Reducing the activity of
microglia could lead to a reduction in their beneficial effects, but this was
not seen when mice were treated with the nasal spray.
In a press release, the study
authors said that “an intake of neural stem cell-derived extracellular vesicles
significantly changed microglia gene expression and reduced the multiple
harmful proinflammatory proteins without affecting the microglia’s ability to
continue clearing the protein buildup related to Alzheimer’s.”
Steven Allder, BMedSci, BMBS,
FRCP, DM, a consultant neurologist at Re:Cognition Health, also not involved in
the stydy, welcomed its findings, noting that:
“The nasal spray appears to
regulate microglia activity effectively. By preventing overactivation of
microglia, it reduces harmful inflammation while allowing these cells to
continue clearing beta-amyloid plaques, which are associated with Alzheimer’s
progression. This balance is crucial because excessive inflammation can lead to
neuron damage, while clearing plaques is necessary to maintain brain health.”
However, he warned MNT of
potential side effects. “While the study shows promising results, possible side
effects need to be evaluated,” he cautioned.
“Adverse reactions could arise
from altering immune cell behaviour, unexpected impacts on other cell types, or
long-term consequences of manipulating the brain’s immune response.
Clinical trials would need to
monitor any immune-related side effects or unexpected impacts on cognition,”
Allder further explained.
Alzheimer’s: ‘Important to consider
different mechanisms of drug delivery’
Kloske stressed the need for
further research to increase the range of Alzheimer’s treatments available.
“Treatments that target
Alzheimer’s from all angles and all stages of the disease are essential, and that’s
why strategic research funding that works to diversify the therapies in the
pipeline is so important,“ she told us.
“It is also important to
consider different mechanisms of drug delivery, such as intranasal delivery as
is used in this research study. All evidence-based paths to treatment targets
and drug delivery methods of Alzheimer’s and all other dementia should be
explored,” added Kloske.
“The Alzheimer’s Association
envisions a future where there are many treatments available that address these
diseases in multiple ways, and can be combined into powerful combination
therapies, most likely in conjunction with brain-healthy lifestyle guidance,”
she told MNT.