Gene Therapy for Alzheimer's Disease and Ethical Aspects of Genome Editing (2020-2021)

Background

The causative factors and the mechanisms behind the onset of Late-onset Alzheimer’s Disease (LOAD) remain unknown. Historically, scientists believed that the A-beta amyloid peptide was the principal cause, but multiple clinical trials targeting A-beta aggregates have not validated this theory. Moreover, treating LOAD at a late stage, in which pathological lesions are already apparent, is thought to diminish the effectiveness of any disease-modifying therapy.

Gaining insight into the biological pathways and molecular basis underlying the causes of LOAD should lead to the development of disease-modifying and preventative treatments. Recently emerged gene-editing technologies provide an unparalleled opportunity for treating LOAD and other neurodegenerative diseases. However, new therapies also bring up many questions regarding safety, economics and ethics. How will gene therapy in LOAD be distributed in a just way? Who will pay for it? What are the implications of administering expensive therapies to patients who are closer to the end of life than the beginning?

Project Description

This project aims to advance research and development of the new gene therapy technologies that will be applicable to treating age-related brain diseases such as LOAD.

The project team will design an experimental plan and participate in laboratory experiments that will test the hypothesis that the association of the APOE gene with LOAD is mediated by dysregulation of APOE expression. The team will focus on modulating APOE expression levels as a therapeutic target for LOAD using innovative genome and epigenome editing tools based on CRISPR/Cas9 technologies. The outcomes of this research will greatly facilitate the development of “smart” drugs for treating LOAD.

In addition, the team will investigate ethical, legal and social questions related to the CRISPR/Cas9 technology and gene therapy for LOAD and other late-onset neurodegenerative conditions. Team members will undertake case studies of earlier gene therapies and trace their development; evaluate the ethical issues associated with the use of gene editing technologies; analyze novel questions of cost and pricing for so-called “one and done” therapies; and mine the literature for approaches to late-onset diseases that have reckoned with both treatment and quality-of-life issues.

Anticipated Outputs

Manuscripts in scientific journals; presentations at professional conferences and to the community; preliminary data establishing evidence of feasibility for external grant applications

Timing

Summer 2020 – Spring 2021

  • Summer 2020: Acquire skills in lab safety, molecular techniques and laboratory procedures; begin initial literature review; define the ethical, legal and social questions regarding gene editing; develop and initiate individual bench-based projects; make final presentations for summer component
  • Fall 2020: Continue independent projects; present progress in lab meeting forums
  • Spring 2021: Complete activities from the fall semester

See earlier related team, Gene Therapy in Alzheimer’s Disease: Novel Therapies and Ethical Aspects of Somatic Gene Editing (2019-2020).

 

Image: Mouse model of Alzheimer's disease, by NIH Image Gallery, licensed under CC BY-NC 2.0

Mouse Model.

Team Leaders

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

/yfaculty/staff Team Members

  • Julio Barrera, School of Medicine-Neurology
  • Logan Brown, School of Medicine-Neurobiology