HomeDate: 2026-03-20
Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by a mutation in the HTT gene that produces a defective protein known as mutant huntingtin (mHTT). This abnormal protein accumulates in brain cells and forms toxic aggregates that gradually damage neurons. Current treatments can only relieve symptoms and do not slow disease progression.
A research team led by Dr. Jen-Tse Huang at the ICAS has developed a new molecular strategy to treat HD. The molecule belongs to a class called PROTACs (proteolysis-targeting chimeras), which guide harmful proteins to the cell’s degradation machinery. Importantly, the newly developed PROTAC can cross the blood-brain barrier and reach brain tissue. Once inside the brain, it selectively binds and eliminates toxic mHTT aggregates and directs them to the proteasome system for degradation. The results demonstrate that this PROTAC effectively reduces mHTT aggregates in neuronal cells and in the brains of HD mice. Treatment also improves motor performance, reduces neuroinflammation, and prolongs survival in the animal model. These findings highlight the therapeutic potential of an aggregate-selective PROTAC strategy for the treatment of HD..
The study was co-first authored by Po-Chao Lu, a Ph.D. student in the AS-TIGP in Chemical Biology and Molecular Biophysics, and Dr. Yung-An Huang, a postdoctoral researcher in Dr. Huang’s laboratory. The PROTAC molecules were synthesized in collaboration with the laboratory of Dr. Jiun-Jie Shie at the ICAS. This research was supported by AS and the NSTC. Core facilities at the IC, including the Mass Spectrometry Facility and Imaging Facility, also provided technical support. The study was published on February 19, 2026, in the Journal of the American Chemical Society.
