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
There are several forms of
dementia, but the most common, Alzheimer’s
disease, currently accounts for
Monoclonal antibody treatments, such as lecanemab and donanemab, are the first
disease-modifying therapies for Alzheimer’s.
They clear the
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
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.”
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
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.
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