Gene Therapy in Alzheimer's Disease: Novel Therapies and Ethical Aspects of Somatic Gene Editing (2019-2020)

This Bass Connections project advanced development of new gene therapy technologies that targeted age-related brain diseases such as Alzheimer’s disease. Team members conducted research on Alzheimer’s disease etiology and mechanisms using cutting-edge genome editing technologies and state-of-the-art stem cell techniques (see diagram).

The overall team was split into three groups. In the Chiba-Falek lab, students investigated the role of APOE and its different isoforms in Alzheimer’s disease pathology by quantifying phenotypic differences between neurons, astrocytes, and microglial-like cells derived from human-induced pluripotent stem cells. Their model provided a strong and malleable system for evaluating novel therapeutic gene therapy approaches in the APOE gene, such as the one being developed in the Kantor lab.

In the Kantor lab, others focused on designing the molecular tools necessary to silence gene expression of APOE4, using CRISPR-Cas9 technology and lentiviral vectors. Their results suggest that we were able to achieve successful downregulation of APOE4.

In the Science and Society program component with Dr. Angrist, students worked on tracing the development of earlier gene therapies in an effort to explore the future challenges associated with finding a disease modifying treatment for AD (a DMT seeks to stop or slow the progression of the disease by making alterations to the pathological steps that lead to the disease).

Timing

Summer 2019 – Spring 2020

Team Outputs

Anna Yang, Boris Kantor, Ornit Chiba-Falek. 2021. "APOE: The New Frontier in the Development of a Therapeutic Target towards Precision Medicine in Late-Onset Alzheimer’s." International Journal of Molecular Sciences 22(3):1244.

Tackling Alzheimer’s with Genetics (Fortin Foundation Bass Connections Virtual Showcase 2020)

Gene Therapy in Alzheimer’s Disease: Understanding the Role of Apolipoprotein E in Late Onset Alzheimer’s Disease (poster by Angela Wei, Dominic Tringali, Gabriella MacDougall, Ashley Kilgore, Ornit Chiba-Falek)

Gene Therapy in Alzheimer’s Disease: Novel Therapies and Ethical Aspects of Somatic Gene Editing (poster by Natalie Asmus, Boris Kantor)  

Gene Therapy in Alzheimer’s Disease: Novel Therapies and Ethical Aspects of Somatic Gene Editing (poster by Anna Yang, Misha Angrist)

Gene Therapy in Alzheimer’s Disease: Novel Therapies and Ethical Aspects of Somatic Gene Editing (poster by Angela Wei, Natalie Asmus, Anna Yang)

This Team in the News

New Bass Connections Project Focuses on Alzheimer’s Disease

Chiba-Falek Selected for Multidisciplinary Bass Connections Project

New Bass Connections Project Researches Alzheimer’s Disease

See related team, Gene Therapy for Alzheimer’s Disease and Ethical Aspects of Genome Editing (2020-2021).

 

Image by Angela Wei

Model showing project focus.

Team Leaders

  • Misha Angrist, Social Science Research Institute
  • Ornit Chiba-Falek, School of Medicine-Neurology
  • Boris Kantor, School of Medicine-Neurobiology

/undergraduate Team Members

  • Natalie Asmus
  • Angela Wei, Biology (BS)
  • Anna Yang, Biology (BS)