Light-Activated Molecule Eliminates Alzheimer’s Protein in Live Mice

Research from the University of Tokyo has demonstrated the efficacy of a small, light-activated molecule in removing clumps of amyloid protein found in the brains of mice with Alzheimer’s disease. If perfected for use in humans, the method could be used as an alternative to immunotherapy and to treat other diseases caused by similar proteins.

The molecule the researchers developed is known as a photo-oxygenation catalyst. Research team members injected it directly into the brains of live mice with Alzheimer’s disease, before illuminating it with a probe for 30 minutes each day for one week. Chemical analysis of the mouse brain tissue showed that the treatment significantly reduced amyloid protein. Additional experiments with human brain samples donated by patients with Alzheimer’s disease supported the possibility of future use in humans.

Experimentation suggests that the molecule-based method treats Alzheimer’s disease in a two-step process.

First, the catalyst destabilizes the amyloid plaques. Oxygenation, or the addition of oxygen atoms, can make a molecule unstable by changing the chemical bonds that hold it together. The catalyst is designed to target the folded structure of amyloid and likely works by cross-linking specific portions called histidine residues. The catalyst is inert until it is activated via near-infrared light.

Consequently, researchers imagine that the catalyst could be delivered throughout the body by injection into the bloodstream and targeted to specific areas using light.

Microglia, immune cells of the brain that clear away damaged cells and debris outside healthy cells, then remove the destabilized amyloid. Researchers observed microglia engulfing oxygenated amyloid and then breaking it down in acidic compartments within the cells, on mouse cells in a dish.

“Our catalyst binds to the amyloid specific structure, not to a unique genetic or amino acid sequence, so this same catalyst can be applied to other amyloid depositions,” said project leader Taisuke Tomita, a professor in the graduate school of pharmaceutical sciences.

Whereas some treatments for Alzheimer’s disease are able to slow the formation of new amyloid plaques, they fail to address existing plaques. Because amyloid begins building up years before symptoms may appear, its elimination is highly important to effective treatment.

The American Society of Clinical Oncology estimates that each year in the U.S., 4000 people are diagnosed with diseases caused by amyloid outside of the brain, collectively known as amyloidosis.

The researchers are currently working to modify the design of the catalyst so that it may be activated by shining light through the skull.

The research was published in Brain (www.doi.org/10.1093/brain/awab058).