[Reading Science] There Is 'Hope' on the Road to Conquering Dementia

In South Korea, a ‘super-aged society,’ the greatest obstacle to health and welfare due to the increasing elderly population is dementia (Alzheimer’s disease). By around 2040, the total national dementia management cost in our country is expected to reach approximately 63.1 trillion won annually. This trend is similar worldwide. Can humanity truly conquer Alzheimer’s? Recent approvals of new therapeutic substances and various research advancements have given the international medical community hope.

Dementia. Stock image.

Emergence of New Technologies

First, new treatments are emerging. A representative example is lecanemab, jointly developed by the U.S. company Biogen and Japan’s Eisai, which received expedited approval from the U.S. Food and Drug Administration (FDA) last January. Expedited approval is a system that grants conditional authorization when treatment effects are demonstrated in severe patients, even if development is not yet complete. This drug showed in clinical trials that it significantly reduces the amount of amyloid-beta (β) protein, the causative substance of Alzheimer’s that accumulates in brain cells, and slows cognitive decline by up to 25%. For severe patients, it resulted in several months of extended life expectancy. However, it must be administered intravenously by a specialized nurse and has side effects such as brain edema and hemorrhage. Previously, in 2021, another drug, aducanumab, also received FDA approval. Although there has been controversy over whether it effectively removes amyloid-beta protein, it undeniably brought great hope to dementia researchers and patients. Especially in the case of lecanemab, it is considered a breakthrough drug because it can prevent deterioration if sufficiently administered to patients diagnosed early. Researchers are now also focusing on developing therapeutic substances targeting the ‘tau protein,’ identified as another causative agent.

Active Research on Combination Therapies

Recently, research has actively begun to examine the effects of combining anti-amyloid and anti-tau therapies. Randall Bateman, a professor of neurology at Washington University, explained in the international journal Nature on the 4th, “Amyloid-beta induces the accumulation of pathogenic tau protein in some way, spreading through the brain. Like extinguishing a wildfire by putting out the fire and removing combustible materials simultaneously, it is appropriate to treat both amyloid-beta and tau protein at the same time.” In fact, Professor Bateman’s research team started an international joint clinical study called ‘Tau NexGen’ last year. The study involves 168 participants aged 30 to 50 who carry genetic mutations that cause Alzheimer’s. The team plans to divide them into two groups: pre-symptomatic carriers and those expected to develop symptoms within 10 years. They will administer lecanemab and anti-tau therapies in different sequences to analyze differences. Those expected to develop symptoms will receive the anti-tau drug (E2814) first for one year, followed by additional lecanemab injections. Conversely, pre-symptomatic carriers will receive lecanemab injections for six months before adding E2814. Through this experimental approach, the team aims to study the effectiveness of combined anti-amyloid and anti-tau therapy and the optimal administration method. They also plan to test other anti-tau drugs besides E2814. The first clinical results are expected to be announced after 2027.

Similar research is underway elsewhere. The U.S. National Institutes of Health (NIH) is also expected to decide within months whether to financially support a clinical trial (ATP) investigating the combined effects of anti-amyloid and anti-tau therapies, jointly promoted by public and private pharmaceutical companies. However, this combination therapy approach is very complex and expensive. The ATP clinical trial is expected to cost hundreds of millions of dollars, and the treatment itself is costly; for example, lecanemab’s annual prescription cost is about $26,500. The administration method requires injections every few weeks, which is very inconvenient for patients. Moreover, to prevent Alzheimer’s disease, treatment must be lifelong.

Research on Various Treatment Methods

Another treatment method that was actively researched but failed in the past, the beta-secretase enzyme inhibitor, is being reconsidered. Beta-secretase is known as the causative enzyme that produces amyloid-beta protein. Research on inhibitors was active until the late 2010s but was halted after devastating failures in clinical trials. The Alzheimer’s Association in the U.S. reviewed these failures in 2021 and concluded that the drugs might have been administered to participants whose symptoms were too advanced, and that lower doses might have avoided side effects, offering hope. In other words, administering the right dose at the right time could be effective. Another failed case, gamma (γ)-secretase inhibitor research, is set to resume early clinical trials this year with NIH support by a private pharmaceutical startup.

Additionally, in Germany, research is underway to improve the brain’s natural immune defense system to eliminate the possibility of Alzheimer’s from the early stages. Alzheimer’s patients experience mutations in the TREM2 gene, which plays a transcriptional role in the brain’s immune system microglia, causing problems such as amyloid-beta protein accumulation. A research team at Ludwig-Maximilians University in Germany is seeking ways to help microglia more effectively clear beta-amyloid protein debris or prevent its spread, alongside anti-amyloid therapy. Professor Christian Haas of Ludwig-Maximilians University said, “We are planning experiments to see what effects occur when antibodies that bind to the TREM2 gene and activate microglia are administered together with anti-amyloid therapy in mouse models.”

In addition to treatments, research on preventive vaccines made using viral vectors or sera is also progressing. Anti-amyloid vaccine research, which was halted after brain inflammation was confirmed in clinical trials in 2002, has recently resumed. There are also researchers attempting gene therapy. Lisa Sparling, a professor at Harvard Medical School, said in Nature, “I have been researching Alzheimer’s treatment for over 30 years, and although it has been frustrating not to find a cure, I believe we are on the right path, but it is still not enough.”