An inert and unreactive gas may not seem like an obvious candidate for treating Alzheimer’s disease, yet a new study in mice suggests that xenon might just be the breakthrough we need.
Xenon is one of the six noble gases. Its name derives from the Greek word for “strange”. In medicine, it has been used as an anaesthetic since the early 1950s and, more recently, to treat brain injuries. It is also being tested in clinical trials for several conditions including depression and panic disorder.
The new study from Washington University and Brigham and Women’s Hospital (the teaching hospital of Harvard Medical School) in the US, has investigated the potential of xenon to treat the brain changes associated with Alzheimer’s.
These changes, which can be found in all brains of people with dementia, include clumps of the proteins amyloid and tau. The connections between neurons, called synapses, are also lost in Alzheimer’s disease and it is these connections between neurons that allow us to think, feel, move and remember.
A final common feature found in the brains of people with Alzheimer’s is inflammation. This is the body’s response to injury or disease and triggers the immune response to heal the damaged tissue.
Usually, inflammation disappears once the tissue is healed. In Alzheimer’s, the inflammation does not go away and the immune responses triggered can then damage healthy brain cells.
All of the above changes give rise to the symptoms of Alzheimer’s, such as memory loss, confusion and mood swings.
We don’t know what causes Alzheimer’s disease, but a leading theory suggests that a build up of amyloid triggers the process that then gives rise to the subsequent changes. So targeting amyloid seems like an obvious approach to treating the disease.
Just over two years ago, we learned of the success of one of these treatments called lecanemab in slowing the rate of decline.
The increase in clumps of proteins and the loss of synapses occur over decades, and it remains to be seen if directly targeting a single protein (either amyloid or tau) would be able to halt disease progression or have a measurable effect on all the characteristic harms.
The brain has several types of cell that work together to support brain function. Neurons are the cells responsible for everything – walking, talking, thinking and breathing. Astrocytes provide energy to the neurons as well as structural support and protective functions.
Other important cells found in the brain are microglia. They are immune cells that help remove pathogens and dead cells, among other activities. However, if they are overactive, they can cause chronic inflammation in the brain.
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Microglia have different states depending on the environment they find themselves in, from an inactive state through to an active state. The difference in these states can be determined both by their appearance and importantly by the functions they perform. For example, active microglia can help clear the accumulated debris, such as unwanted proteins, cells and infections.
The scientists in this latest study used mice that have the same brain changes seen in Alzheimer’s to investigate the role of microglia. A specific active state of microglia that was associated with inflammation was identified. The scientists gave the mice xenon gas to inhale, which changed the state of their microglia.
This altered state allowed the microglia to surround, engulf and destroy amyloid deposits. It also changed the function of these microglia so that they didn’t drive further inflammation.
The researchers also found a reduction in the number and size of amyloid deposits found. All these changes were associated with the altered microglial state.
But what of the other changes seen in the brains of people with Alzheimer’s? The study also suggested Xenon inhalation could reduce brain shrinkage (a common feature of Alzheimer’s disease) and lead to an increase in support of the connections between neurons. And in all the mice studied, markers of the excessive inflammatory response were reduced.
So, overall, the research suggests that inhaling xenon triggers the active microglia to change from an Alzheimer’s disease-type active state to a pre-Alzheimer’s state. This pre-Alzheimer’s disease state promotes the clearance of amyloid deposits and reduces the cell messengers that cause excessive inflammation.
New hope
There are no drugs that target microglia in Alzheimer’s and inroads have been made in addressing amyloid accumulation. Current drugs aimed at reducing amyloid in the brain offer a modest reduction in amyloid deposits and rate of decline.
Amyloid treatment will improve over time, but what of the other changes that occur in the brain, such as the deposits of tau, brain shrinkage and loss of synapses?
The new research opens up the possibility of targeting a cell type that has the innate potential to affect all of these characteristic harms.
Clinical trials in healthy volunteers are expected to begin this year. If these findings hold up, xenon could offer a completely new approach to this mind-robbing disease. It would be a treatment that doesn’t directly target amyloid, but rather aims to reset the brain’s immune response to counteract all of the disease’s destructive changes. Stranger things have happened.
Ritchie Williamson, Director of Research, Associate Professor in Therapeutics, University of Bradford
This article is republished from The Conversation under a Creative Commons license. Read the original article.
