Screen for Modulators of Abeta Toxicity in iPSC Neurons
Many past attempts to develop treatments for Alzheimer’s disease (AD) have focused on just one characteristic of the disease, the build up of a protein known as amyloid beta (abeta, or Aβ), and have assumed that all patients will respond to new treatments in the same way. We have developed a series of laboratory tests that will enable us to look for ways to potentially correct a whole range of problems associated with Alzheimer’s disease. We also propose using cells derived from several patients in order to determine whether individual patients differ in how AD manifests and how they might respond to new treatments. The project combines a series of modern technologies and a deep understanding of AD that will, for the first time, enable us to answer some very practical questions about how we can make future AD treatments more effective.
The goal of our project is to identify potential new therapeutic paths for treating AD. We are doing this using multiple screening platforms. Unlike many other screens, we are using brain cells derived from different people. We use stem cells derived from living humans, and then, using induced pluripotent stem cell technology, we direct those cells to become the cells most affected by AD, namely, neurons and glia. We then look at multiple features of these cells in response to toxic proteins that are central to AD. By investigating cells from multiple people, we are investigating if and how different people’s brain cells respond to these toxic proteins. In addition, through screening strategies, we are looking for potential drugs that prevent toxic effects of these species. We then are investigating whether cells from different people respond differently to potential drug treatments. Once our study is complete, we hope that we will have identified novel therapeutic paths for Alzheimer’s disease, and identified which sets of patients are most likely to respond to those interventions.
About the Researcher
Tracy Young-Pearse, PhD, received her undergraduate degree from Skidmore College in her home town of Saratoga Springs, NY. She went on to enter the Biomedical and Biological Sciences program at Harvard Medical School, where she received her PhD in genetics under the guidance of Connie Cepko, PhD. She then completed a postdoctoral fellowship in the Center for Neurologic Diseases at Brigham and Women’s Hospital and Harvard Medical School. Tracy is now an assistant professor of neurology at Harvard Medical School and Brigham and Women’s Hospital, where she runs her laboratory. The long -term goals of the Young-Pearse lab are to understand the in vivo functions of genes identified in neurodegenerative and developmental disorders of the human brain.
"I remember learning about Alzheimer’s disease (AD) as a child, and being terrified that someone in my family might get the disease and not remember me. As I have grown older and learned more about the disease and the available treatments, I have discovered that my fears as a child were not unreasonable. The disease is devastating and incredibly common. Through my work in the lab, trying to understand the mechanisms, I have met many people who suffer from AD and have observed first hand the impact upon their families.
We know so much about the processes involved in this disease, and yet there still is so much more to understand if we are going to stop it. In the past year, there have been some glimmers of hope from trials of new interventions. However, we must never rest in our studies of AD, even if new trials are successful, since not everyone may respond to the new interventions. We want to be ready with new assays that can test who would be most responsive to these new treatments, and develop new therapies that can help those who are not responsive."
First published on: July 10, 2015
Last modified on: July 1, 2018