The global prevalence of dementia is on the rise, driven by population growth and aging. Forecasts suggest that nearly 152.8 million people will have dementia by 2050, with Alzheimer's disease accounting for up to 70% of cases. While current treatments aim to manage symptoms, emerging therapies are offering hope for slowing disease progression. Two monoclonal antibody treatments, lecanemab and donanemab, have shown promise as the first disease-modifying therapies for Alzheimer's, targeting beta-amyloid plaques that contribute to cognitive decline. Despite these advancements, concerns remain about their high cost and potential side effects, leading researchers to explore alternative methods.

A study from Texas A&M University College of Medicine has introduced a nasal spray designed to combat neuroinflammation, a key factor in Alzheimer's progression. Published in the Journal of Extracellular Vesicles, this research demonstrates that the spray delays disease development in a mouse model. If similar results are observed in humans, the treatment could potentially extend the progression-free period by up to 15 years.

Microglia and Astrocytes: A Double-Edged Sword

Microglia and astrocytes, essential immune cells in the brain, play a crucial role in the pathology of Alzheimer's disease. In a healthy brain, these cells maintain neural function by removing damaged tissues and protecting nerve cells. However, in Alzheimer's, they become overactive after initially clearing beta-amyloid plaques, leading to widespread inflammation and neuronal destruction.

The researchers administered an anti-inflammatory treatment via nasal spray in a mouse model exhibiting early Alzheimer’s-like symptoms. The spray contained extracellular vesicles derived from stem cells. These vesicles were designed to target microglia and astrocytes, reducing inflammation and the accumulation of harmful brain proteins.

Promising Results in Mice

The study involved both genetically modified mice predisposed to Alzheimer's symptoms and wild-type mice. At 3 months old, the mice received two doses of the nasal spray or a placebo one week apart. Researchers euthanized a subset of mice 72 hours after the second dose to analyze cellular activity. Behavioral tests were conducted on the remaining mice over the next month to assess cognitive functions.

By the age of 4.5 months, untreated transgenic mice displayed typical Alzheimer's markers, including increased beta-amyloid plaques, heightened microglial activity, and inflammation. However, the treated mice exhibited significantly reduced inflammation and plaque buildup, particularly in the hippocampus, a region critical for memory and learning. Cognitive and mood improvements were also noted in treated mice compared to the control group.

Dr. Clifford Segil, a neurologist at Providence Saint John’s Health Center, remarked on the significance of plaque-reducing treatments but emphasized the need for further investigation. "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," he explained.

Potential Implications for Human Treatment

The nasal spray’s mechanism appears to effectively reduce harmful inflammation without compromising the beneficial functions of microglia, such as clearing protein buildup. According to the study authors, "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."

Although the study offers promising insights, experts caution against overinterpreting the findings without clinical trials in humans. Dr. Steven Allder, a consultant neurologist at Re

Health, highlighted the importance of understanding potential risks. “While the study shows promising results, possible side effects need to be evaluated,” he noted. Altering immune cell behavior could lead to unexpected consequences, necessitating careful monitoring during human trials.

Expanding the Horizon of Alzheimer's Therapies

This research underscores the importance of diversifying treatment approaches for Alzheimer's disease. According to Dr. Courtney Kloske, director of scientific engagement at the Alzheimer's Association, developing a range of therapies targeting different aspects of the disease is crucial. "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 stated.

The study’s focus on intranasal delivery also opens doors to alternative drug administration methods. Intranasal therapies offer a non-invasive and efficient route to target the brain directly, bypassing the blood-brain barrier. This approach could complement other treatments, potentially forming part of combination therapies alongside lifestyle interventions.

While it remains early days for plaque-reducing treatments, this innovative nasal spray represents a step forward in the fight against Alzheimer’s. Continued research and clinical trials will determine whether such therapies can translate into meaningful improvements for patients, offering hope for a future with more effective Alzheimer’s interventions.

Reference:

1. Journal of Extracellular Vesicles, vol. 13, no. 5, 2024, article e12519. Accessed November 25, 2024. https://isevjournals.onlinelibrary.wiley.com/doi/10.1002/jev2.12519.

(Input from various sources)

(Rehash/Yash Kamble/MSM)