(128f) Building Brains: Marrying Engineering & Medicine in the Fight Against Alzheimer Disease

Neurodegenerative diseases such as Alzheimer disease incur high caregiver costs and significantly diminish economic output. Treating them is an urgent priority. Unfortunately, there are no treatments. Drug discovery has been stymied by the absence of reliable pre-clinical screens for identifying promising leads, which implies that results from pre-clinical testing do not translate well to the clinic. There is a clear requirement to develop better pre-clinical screens to test lead compounds in a brain- specific context. To this end, we are developing a process to manufacture engineered brain tissue whose microenvironment closely mimics the environment within degenerated brains. We refer to healthy brain tissues produced via this method as ‘cerebroids’, and assembly of these tissues is achieved in a 2-stage process that employs an innovative method for stem cell differentiation and cellular assembly. The cerebroids are manipulated in the third stage to elicit neurodegeneration. Herein, we are investigating two complementary approaches that facilitate seamless scale-up. Our work combines concepts and insights from stem cell bioengineering, tissue biomanufacturing, and biomedical instrumentation. The manufactured tissue incorporates all clinically relevant cell types and sub-tissues, and we are partnering with a Vancouver-based company to commercialize the manufacturing platform. The cerebroids platform could prove to be a game changer for pharmaceutical testing and molecular medicine.