New drug candidate disrupts the link between herpes virus and Alzheimer’s disease

Studies suggesting that certain viral infections may influence the onset of Alzheimer's diseases are gaining attention. In this context, a domestic research team has succeeded in breaking the link between viral infection and Alzheimer's disease using a new treatment candidate.

Dr. Ok Sarah Shin, a professor in the Department of Convergence Medicine at Korea University College of Medicine (KUCM), leads the research team together with Dr. Soo-Jin Oh from KUCM and Professor Jean-Ho Yun from Dong-A University College of Medicine. Dr. Shin's team has identified the association between viral infection and Alzheimer's disease and blocked the connection using the new drug candidate ALT001.

Alzheimer's disease is one of the most common types of dementia. Recent studies suggest that neurotropic viruses such as Herpes Simplex Virus Type 1 (HSV-1) may influence the development of neurodegenerative diseases. However, how HSV-1 infection accelerates neurodegenerative phenotypes has not been clearly identified.

The research team first analyzed the effects of HSV-1 infection on microglia, the brain's immune cells. Using various experimental systems-including mice, human-derived microglia, microglia-neuron co-culture models, and brain organoids (artificial mini-brain models)-they confirmed that HSV-1 infection disrupts mitophagy, the intracellular clearance process that removes damaged mitochondria, thereby impairing mitochondrial function. The team also demonstrated that the infection interferes with phagocytosis, the process of clearing amyloid aggregates-protein clumps that accumulate in the brain-which can accelerate neurodegenerative diseases.

Based on these findings, the mitophagy enhancer ALT001, developed by the research team, showed effects in suppressing HSV-1 infection and alleviating neuroinflammation. ALT001 improved mitophagy function in virus-infected microglia. As a result, it effectively inhibited viral replication while reducing neuroinflammatory responses. It was also confirmed to enhance the microglia's ability to clear amyloid aggregates.

Professor Shin stated, "This study is highly significant as it not only demonstrates at a molecular level that viral infection can worsen neurodegenerative diseases, including Alzheimer's, but also presents a new treatment strategy. In particular, identifying the impact of HSV-1 infection on mitophagy in microglia is a distinct achievement compared to previous neuron-focused research. ALT001 could be applied in the future to treat various viral neurological disorders."

Meanwhile, the findings of this study were recently published in the prestigious international journal Theranostics (Impact Factor 12.4) under the title: "Pharmacological targeting of mitophagy via ALT001 improves herpes simplex virus 1-mediated microglial inflammation and promotes amyloid beta phagocytosis by restricting HSV1 infection."