PC12 Cells Engineered for Screening Drugs to Treat Huntington's Disease

UCLA researchers have developed a cell-based screening assay to identify chemical compounds that protect against Huntington's Disease-mediated cell death.

Huntington's disease (HD) is characterized by progressive deficits in motor control and cognitive deterioration. It is caused by an increase in CAG nucleotide repeats in the Huntingtin gene, resulting in an expansion of a polyglutamine region in the encoded Huntingtin protein (Htt). This mutant Htt protein is highly toxic to neurons and results in substantial cell death in the brain, but its mechanism of action is unknown. There is currently no treatment to prevent or palliate the progress of HD. Identification of clinically effective drugs that would decrease symptoms or increase survival would represent a major advance.

Researchers at UCLA have developed a cell-based screen to test chemical compounds for their ability to protect against Huntington's Disease (HD)-related cell death. The researchers have engineered neuronal cell lines (PC12/pBWN:Htt ex1(Q103)-EGFP cells and PC12/pBWN:Htt ex1(Q25)-EGFP) that expresses mutant Huntingtin protein (Htt) in an inducible manner. These cells exhibit rapid and extensive cell death after induction of mutant Htt. This assay provides an important tool for the discovery of drugs to treat HD and to increase our understanding of the pathogenic mechanisms that underlie disease progression.

The researchers have tested and validated the system for its ability to identify compounds that protect against mutant Htt-mediated cell death.