Summary: Researchers have developed a promising nasal spray therapy targeting neuroinflammation in Alzheimer’s disease, potentially delaying its progression by over a decade. Using extracellular vesicles derived from neural stem cells, the treatment reduced inflammation and protein build-up in the brain in early-stage Alzheimer’s animal models.
By altering the activity of microglia — the brain’s immune cells — this therapy appears to curb damaging inflammation without impairing the removal of harmful proteins. If successful in human trials, the therapy could significantly improve the quality of life and delay severe cognitive decline in Alzheimer’s patients.
Key Facts:
- Targeted Therapy: The nasal spray delivers therapeutic extracellular vesicles that reduce inflammation and plaque buildup in the brain.
- Microglia Impact: Treatment altered microglia to reduce harmful inflammation while maintaining their plaque-clearing function.
- Long-Term Potential: The therapy may delay Alzheimer’s progression by 10-15 years, offering significant improvement in quality of life.
Source: Texas A&M
A new therapy may delay Alzheimer’s disease progression by years, according to a study by researchers at Texas A&M University College of Medicine.
Published in the Journal of Extracellular Vesicles, the research aims to explore treatment options for Alzheimer’s, which constitutes the most common form of dementia and is a leading cause of death among those aged 65 or older, afflicting nearly 7 million Americans.
Utilizing a nasal spray to non-invasively target cells perpetuating chronic neuroinflammation, researchers found decreased inflammation in the brain and a reduction in the build-up of plaques and proteins thought to be linked to the progressive loss of neurons in the brain, characteristic of Alzheimer’s.
“This approach is effective because the cargo carried by these extracellular vesicles could reduce the neuropathological changes in the brain,” says Ashok K. Shetty, Ph.D., a University Distinguished Professor and associate director at the Institute for Regenerative Medicine in the Department of Cell Biology and Genetics.
Shetty, collaborator Madhu LN, Ph.D., and their colleagues, administered the nasal spray treatment to an animal model in the early stages of Alzheimer’s.
Compounding their promising results, researchers also found that microglia, immune cells within the brain, incorporated the intranasally administered neural stem cell-derived extracellular vesicles.
In Alzheimer’s, microglia activate to cause inflammation and clear Alzheimer’s-related plaques from the brain. This initially helpful function becomes problematic over time, Shetty says.
“Prolonged activation causes them to lose their normal function and begin to harm neurons, leading to progressive neuron loss.”
Findings indicate 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, Madhu says.
Shetty has filed a patent on the intranasal application of neural stem cell-derived extracellular vesicles for treating Alzheimer’s and other neurological disorders.
He says the research conducted in his lab — funded by the National Institute on Aging — already has inspired further studies, and he hopes successful research could point toward treatment delaying Alzheimer’s-related changes and severe cognitive issues by 10 to 15 years after initial diagnosis.
“Our journey to advance the application of this therapy for Alzheimer’s disease is just beginning,” he says.
About this Alzheimer’s disease research news
Author: Laura Tolentino
Source: Texas A&M
Contact: Laura Tolentino – Texas A&M
Image: The image is credited to Neuroscience News
Original Research: Open access.
“Extracellular vesicles from human-induced pluripotent stem cell-derived neural stem cells alleviate proinflammatory cascades within disease-associated microglia in Alzheimer’s disease” by Ashok K. Shetty et al. Journal of Extracellular Vesicles
Abstract
Extracellular vesicles from human-induced pluripotent stem cell-derived neural stem cells alleviate proinflammatory cascades within disease-associated microglia in Alzheimer’s disease
As current treatments for Alzheimer’s disease (AD) lack disease-modifying interventions, novel therapies capable of restraining AD progression and maintaining better brain function have great significance.
Anti-inflammatory extracellular vesicles (EVs) derived from human induced pluripotent stem cell (hiPSC)-derived neural stem cells (NSCs) hold promise as a disease-modifying biologic for AD.
This study directly addressed this issue by examining the effects of intranasal (IN) administrations of hiPSC-NSC-EVs in 3-month-old 5xFAD mice. IN administered hiPSC-NSC-EVs incorporated into microglia, including plaque-associated microglia, and encountered astrocyte soma and processes in the brain.
Single-cell RNA sequencing revealed transcriptomic changes indicative of diminished activation of microglia and astrocytes.
Multiple genes linked to disease-associated microglia, NOD-, LRR-, and pyrin domain-containing protein 3 (NLRP3)-inflammasome and interferon-1 (IFN-1) signalling displayed reduced expression in microglia.
Adding hiPSC-NSC-EVs to cultured human microglia challenged with amyloid-beta oligomers resulted in similar effects. Astrocytes also displayed reduced expression of genes linked to IFN-1 and interleukin-6 signalling.
Furthermore, the modulatory effects of hiPSC-NSC-EVs on microglia in the hippocampus persisted 2 months post-EV treatment without impacting their phagocytosis function.
Such effects were evidenced by reductions in microglial clusters and inflammasome complexes, concentrations of mediators, and end products of NLRP3 inflammasome activation, the expression of genes and/or proteins involved in the activation of p38/mitogen-activated protein kinase and IFN-1 signalling, and unaltered phagocytosis function.
The extent of astrocyte hypertrophy, amyloid-beta plaques, and p-tau were also reduced in the hippocampus. Such modulatory effects of hiPSC-NSC-EVs also led to better cognitive and mood function. Thus, early hiPSC-NSC-EV intervention in AD can maintain better brain function by reducing adverse neuroinflammatory signalling cascades, amyloid-beta plaque load, and p-tau.
These results reflect the first demonstration of the efficacy of hiPSC-NSC-EVs to restrain neuroinflammatory signalling cascades in an AD model by inducing transcriptomic changes in activated microglia and reactive astrocytes.
