New drug blocks herpes virus and Alzheimer’s disease

South Korean researchers have discovered a promising new approach that can prevent or treat Alzheimer’s disease by targeting the link between herpes virus infection and brain inflammation.

The study, published in Theranostics, demonstrates how a new drug candidate called Alt001 can effectively prevent herpes simplex virus (HSV1) from damaging brain immune cells and enhances its ability to clear up harmful protein accumulation associated with neurodegenerative diseases. This dual mechanism of action, which fights viral infection while restoring normal brain immune function, has made significant progress in understanding how infection leads to Alzheimer’s disease and provides potential new pathways for affected patients.

The study, led by Dr. Ok Sarah Shin of the Korean University School of Medicine and Professor Jean-Yun of the East A University School of Medicine, provides compelling evidence that viral infections may play a more important role in neurodegenerative diseases than previously recognized. Their work specifically targets microglia, the immune cells of the brain, which play a crucial role in removing toxic proteins such as amyloid (Aβ), such as amyloid β (Aβ) accumulated in Alzheimer’s disease.

How herpes virus destroys brain immune cells

The team’s investigation revealed a complex chain of events where HSV1 infection hurts brain health. Using a variety of experimental models, including mouse cells, human stem cell-derived microglia and complex brain organ models, the researchers accurately tracked how the virus disrupted normal immune function.

Their findings suggest that HSV1 is specifically targeting a critical cellular cleaning process called mitochondria, which usually removes damaged mitochondria (the energy-producing component of the cell). The virus uses a protein called US3 to interfere with this cleaning process, resulting in dysfunctional mitochondria accumulation, triggering inflammation and impairing normal cellular function.

This destruction can have a series of harmful effects. Infected microglia transfer to an inflammatory state, producing higher levels of proinflammatory molecules such as IL-6, IL-1β and TNF-α. At the same time, the virus greatly reduces the ability of these immune cells to perform normal cleanup duties, especially their ability to remove Aβ protein aggregates associated with Alzheimer’s disease.

Alt001: Restoring cell cleanup mechanism

The team found that the experimental drug ALT001 activated another mitochondrial pathway that bypassed viral blockade. The drug works through a mechanism called ULK1/RAB9-dependent mitochondria that essentially provides a “back-up” cleaning system when the main mitochondrial pathway is compromised.

When infected cells were treated with Alt001, the researchers observed several significant effects:

• Restores mitochondrial structure and function in infected cells
• Significant reduction in HSV1 replication and viral spread
• Enhanced interferon response, enhancing antiviral immunity
• Reduced production of inflammatory cytokines
• Restoring the ability of microglia to phagocytize and remove Aβ protein aggregates
• Prevent cell coculture and neuronal damage in brain organ models

Transcriptome analysis further showed that Alt001 treatment transferred infected microglia from disease-related inflammatory states to normal homeostasis, which essentially “reset” these immune cells despite persistent viral stress.

Learn about the new paradigm for Alzheimer’s disease

This study adds significant weight to emerging theories that infections may help or speed up neurodegenerative diseases like Alzheimer’s. Previous epidemiological studies have shown an association between HSV1 infection and the risk of Alzheimer’s – more than 70% of Alzheimer’s cases show potential evidence of HSV1 infection, but the exact mechanism remains unclear.

“This study is very important because it not only demonstrates at the molecular level that viral infection can worsen neurodegenerative diseases, including Alzheimer’s, but also proposes a new therapeutic strategy,” Professor Shin said. “In particular, determining the effect of HSV-1 infection on microglia in microglia is a unique achievement compared to previous studies using neurons. Alt001 can be used to treat various viral neurological diseases in the future.”

Beyond Alzheimer’s: A wider application

The implications of this study go beyond Alzheimer’s disease. The team’s findings suggest that Alt001 may provide potential therapeutic benefits for other diseases that are damaged by mitochondria or viral infection.

Interestingly, Alt001 showed an effective antiviral effect on HSV1 than Acyclovir in laboratory tests. This increases Alt001’s potential to become a treatment for herpes simplex encephalitis, a severe brain infection caused by HSV1.

While clinical trials are necessary to confirm the safety and efficacy of Alt001 in humans, this study opens up new avenues that promise to treat neurodegenerative diseases by addressing both viral triggering and immune dysfunction. As evidence continues to link infection with neurodegenerative diseases, this approach may eventually change the way we conceptualize and treat diseases such as Alzheimer’s disease in the future.