Xenon to the rescue?

Xenon is one of the noble gases. If you remember back to high school chemistry class, the noble gases are all on the right side of the periodic table in group 18: helium (atomic number 2), neon (atomic number 10), argon (atomic number 18), krypton (atomic number 36), xenon (atomic number 54), and radon (atomic number 86). When I was in high school, they were called “inert gases” because they are relatively resistant to forming salts or other chemical compounds, but the term “noble gas” seems now to be preferred.

Xenon stands out among the other noble gases in several ways. For one thing, it appears to have both hydrophobic and hydrophilic properties that allow the xenon molecules to mix freely in both aqueous (water-based) and lipophilic (fatty) surroundings. Xenon readily crosses the blood brain barrier, and it has been used as an inhalation anesthetic since the early 1950s. It does not appear to have any serious side effects except for the very high cost, at least three times higher than other comparable anesthetics. Xenon has also been shown to be neuroprotective in animal models of traumatic brain injury, and this protection appears to be mediated by N-methyl-D-aspartate (NMDA) receptor antagonism.

In an impressive paper published recently in Science Translational Medicine, the authors propose that xenon may also be useful in treating Alzheimer’s disease. They studied the effect of xenon gas in three transgenic mouse models of Alzheimer’s by moderating the function of microglial cells in the brain. The microglia are the scavengers of the brain. They normally clean up messes in the brain such as beta-amyloid plaques. As Alzheimer’s disease progresses, microglia appear to lose their ability to break down beta-amyloid proteins. In this new study, xenon helped microglia regain that ability and also reduced inflammation in the brain. In two mouse models that express proteins that are hallmarks of Alzheimer’s, beta-amyloid and tau, mice exposed to xenon had lower levels of the two proteins. In transgenic mice with APOE-4 allele, animals treated with xenon did better at tests of cognition and had less deterioration in the brain. 

I know, I know. We have been down this road before. Many, many potential drugs have shown benefits in animal models of Alzheimer’s but have then failed completely in human trials. But something about xenon is tantalizing. And unlike most Alzheimer’s drugs, xenon appears to have no serious side effects. Time for a clinical trial? You bet. A phase 1 trial is already recruiting. Sign me up!