A new treatment strategy emerges
Positron emission tomography (PET) image of the brain of an Alzheimer’s disease patient. The part marked with an arrow (inside the white border) means the accumulation of amyloid beta protein, which is pointed out as one of the causes of Alzheimer’s disease. Provided by the National Institutes of Health (NIH)
Alzheimer’s disease, which accounts for the highest proportion of dementia among degenerative brain diseases, is a disease that burdens not only patients but also their families and society as a whole. According to the International Alzheimer’s Association, 24 million people worldwide suffer from Alzheimer’s disease. The development of treatments targeting various causes of disease is speeding up, but there is no perfect cure yet.
According to the international journal ‘Nature’ on the 13th, a new treatment strategy for Alzheimer’s disease is drawing attention from the academic world. It is a treatment that targets the protein that causes the disease at the same time or uses enzymes and genes. It is attracting attention that it will bring a turning point in the treatment of Alzheimer’s disease, a disease that mankind has not yet conquered along with cancer.
● Simultaneous targeting of tau protein and amyloid beta protein
Scientists have pointed out tau protein and amyloid beta (Aβ) protein, which accumulate in the brain, as the main causes of Alzheimer’s disease. Until now, treatment strategies targeting each protein have been studied, but recently, treatment research targeting two types of proteins at the same time is actively underway.
First of all, by paying attention to the entanglement of tau protein, anticipation is rising for a treatment aimed at simultaneously removing the entanglement of tau protein and amyloid beta protein. This is because the hypothesis that Alzheimer’s disease is worsened by the complex action of these two proteins is gaining strength.
Tau protein, which is mainly present in neurons of the central nervous system, plays a role in maintaining the stability of microtubules, which are transport channels for neurotransmitters. In a normal state, it helps maintain brain function, but when this protein is misfolded, toxic substances are secreted and brain function deteriorates.
In particular, it has been confirmed that accumulation of amyloid beta protein acts as a trigger to cause misfolding of tau protein. In the case of amyloid beta protein, which is mainly present in the brain cortex, the effect of ‘Aducanumab’, a treatment that removes this protein, was found to be insignificant.
Lee Jae-hong, professor of neurology at Seoul Asan Medical Center, said, “Folding of tau protein and accumulation of amyloid beta protein are commonly observed in patients with Alzheimer’s disease. there is,” he said.
Clinical trials for a treatment that simultaneously resolves tau protein tangles and amyloid beta protein accumulation have recently begun. A typical example is Tau NexGEN, a treatment that a research team at St. Washington University in the United States launched a clinical trial last year. It is expected that the first clinical trial results will be released after 2027 at the earliest.
● Experiments on treatments using enzymes and genes are also active.
Treatment strategies using enzymes or genes are also attracting attention. It is a treatment that focuses on ‘beta-secretase’, which is involved in the secretion of amyloid beta protein, and ‘gamma-secretase’, an enzyme that has the function of cutting this protein.
In 2021, the Alzheimer’s Association in the United States obtained the results of clinical trials of treatments that failed after targeting these enzymes and shared them with the academic community. The academic world that analyzed the clinical trial pointed out that the disease of the participants was excessively advanced as the cause of the failure of the clinical trial at the time, and the development of a treatment focusing on enzymes is being refocused. Acta, a new American pharmaceutical company, is currently developing a treatment with support from the National Institutes of Health (NIH).
Research is also in full swing to find clues to the treatment of Alzheimer’s disease in genes. A research team at Maximilian University in Germany is conducting a clinical trial for a treatment that promotes the function of ‘TREM2’, a gene that regulates the accumulation of amyloid beta protein in the brain’s immune system. US pharmaceutical company Lexeotherapeutics is researching a protein involved in fat metabolism, which is closely related to Alzheimer’s disease. It is a method of suppressing the action of the gene ‘APOE4’, which is believed to increase the risk of Alzheimer’s disease, and artificially injecting the gene ‘APOE2’, which reduces the risk of Alzheimer’s disease. The clinical trial, which was conducted with 15 participants, is expected to produce first results in 2028.
Shin Hee-seop, honorary researcher at the Institute for Basic Science, said, “Alzheimer’s disease has been identified as being caused by complex causes such as abnormal activity of glial cells, blood circulation, and inflammatory reactions.” said.
Donga Science Reporter Park Jeong-yeon hesse@donga.com