Expectations for new treatments for Alzheimer's disease
University of Tokyo succeeds in removing Amyloid β by photoirradiation with a photooxygenation catalyst in the brain

Alzheimer's disease is characterized by formation of amyloid β aggregates and neurofibrillary tangles of phosphorylated tau protein, which lead to nerve cell death.

Therefore, Professor Taisuke Tomita, Lecturer Yukiko Hori, and Graduate Student Shuta Ozawa of the Graduate School of Pharmaceutical Sciences Neuropathology and Neuroscience Laboratory; Professor Motomu Kanai and Yohei Sohma, Group Leader (at the time of research) of the research group by Pharmaceutical Function of the Laboratory of Synthetic Organic Chemistry at the University of Tokyo developed a photooxygenation method that artificially adds oxygen to aggregated amyloid β using a photooxygenation catalyst activated by light irradiation. They showed that the aggregation of amyloid β can be suppressed and amyloid β can be removed from the brain of a model mouse via this method. This method is expected to become a new therapeutic modality for Alzheimer's disease, and the research outcome was published in the journal Brain.

It is reported that 60-70% of patients with dementia have Alzheimer's disease. Amyloid β accumulated in the brain forms aggregates and causes cytotoxicity and neurofibrillation, followed by cognitive dysfunction. Therefore, if amyloid β can be removed from the patient, Alzheimer's disease can be prevented.

The four currently used drugs target neurotransmitters. Antibody drugs are promising candidate drugs that target amyloid β and tau. When the antibody enters the brain, microglia (macrophages in the nervous tissue) phagocytose amyloid β. However, owing to the large molecular weight of the antibody, it has a low probability of crossing the blood-brain barrier. Furthermore, because it is a biological product, it is expensive. Therefore, the research group developed the photooxygenation method , which adds oxygen to the amyloid β fibers that accumulate in the brain by using a photooxygenation catalyst and light irradiation. Oxygenated amyloid β has low agglutination ability and reduced cytotoxicity.

In the experiment, a photooxygenation catalyst was directly introduced into the brain of an Alzheimer's disease model mouse, in which amyloid β accumulates. The brain was then irradiated with light once a day for 7 days. In the in vitro experiment, only an aggregation inhibitory effect was obtained, whereas in the in vivo experiment, amyloid β disappeared sooner than expected. A detailed analysis revealed that microglia phagocytose oxygenated amyloid β, a mechanism similar to that of antibody drugs.

Professor Tomita stated, "This time, we added the compound directly to the brain and irradiated it with light. However, a paper published in March reported that when an oxygenation catalyst is inserted from a vein, it migrates into the brain and successfully reduces amyloid β in 4 months by non-invasive light irradiation from above the scalp. The challenge for clinical practice is light irradiation, but the point is to provide energy, so we are thinking of supplying energy by using a system that can perform non-invasive in vivo measurements such as ultrasonic waves, PET, and CT. Oxygen can also be applied to diseases caused by amyloid formation and accumulation other than that of amyloid β, such as Parkinson's disease and amyotrophic lateral sclerosis."