PSC-derived iCell Neurons have been used to model Alzheimer’s disease at GlaxoSmithKline.
The research was performed by the lab of Zhong Zhong, Ph.D., head of discovery in the regenerative medicine group within GlaxoSmithKline (GSK).
The GSK researchers used CDI’s commercially available iCell Neurons, comprised of human neurons with characteristic forebrain markers, to model neuronal loss in human AD brains by exposing them to ?-amyloid 1-42 (A?1-42), a peptide known to be associated with AD.
A?1-42 builds up in the brains of those susceptible to the disease and acts as a plaque that causes progressive memory loss and cognitive decline.
Because iCell Neurons meet tight quality standards and are available commercially in large quantities, the researchers used this AD cellular model to screen hundreds of compounds and ultimately identified several small molecules that inhibited the A?1-42 toxicity.
This is the first known use of human iPSCs to model Alzheimer’s disease through A?1-42 toxicity in a drug screen and demonstrates the value of commercial-scale quantities of human iPSC-derived cells for use in disease modeling, drug discovery, and target validation.
“Prior to iCell Neurons, the research models available to study AD included mice, human postmortem tissues, and immortalized neuronal cell lines. These models all have severe physiologic and genetic limitations,” said Emile Nuwaysir, chief operating officer of CDI and co-author on the paper.
“To make rapid progress in AD research, it is critical to have a cellular model that accurately recapitulates normal and disease pathology. We were excited to work with a team as talented as Dr. Zhong’s to perform this study, which demonstrated that when you have a physiologically relevant and reproducible system like iCell Neurons as the basis for your screening platform, you can make rapid and dramatic discoveries.”
