Smart prodrug targets Alzheimer's disease using hydrogen peroxide signals

A substance that worsens dementia has become a "switch" that initiates treatment. KAIST researchers have developed a new therapeutic approach that uses hydrogen peroxide (H₂O₂), a reactive oxygen species that damages cells and increases in the brains of patients with Alzheimer's disease, to activate a drug selectively in diseased brain tissue. The team also confirmed improvements in cognitive function through animal experiments, presenting a new possibility for next-generation dementia treatment.

KAIST (President Kwang Hyung Lee) announced on the 2nd that a research team led by Professor Mi Hee Lim of the Department of Chemistry, in collaboration with Professor Mingeun Kim of Chonnam National University, Dr. Chul-Ho Lee and Dr. Kyoung-Shim Kim of the Korea Research Institute of Bioscience and Biotechnology, and Dr. Young-Ho Lee of the Korea Basic Science Institute, has developed a prodrug that is activated selectively in the diseased brain in Alzheimer's disease and confirmed its therapeutic effects through animal experiments.

A prodrug is a drug that initially has minimal therapeutic effect but is converted into an active therapeutic agent only under specific conditions inside the body. In this study, the prodrug was designed to be activated only when it encounters hydrogen peroxide, which increases in the brains of patients with Alzheimer's disease, allowing it to function as a "smart therapeutic agent" that selectively acts in diseased brain tissue.

In the brains of Alzheimer's disease patients, hydrogen peroxide, which damages cells, is elevated above normal levels. Until now, it has generally been regarded only as a harmful substance that should be removed. However, the research team devised a method to use it instead as a signal that activates a drug.