Treating Alzheimer's with Gene Therapy and the Ethical, Legal and Social Implications (2021-2022)

Background 

The causative factors and the mechanism behind the onset of Late-onset Alzheimer’s Disease (LOAD) remain unknown. Historically, the common view has been that the A-beta amyloid peptide is the principal cause; however, multiple clinical trials targeting A-beta aggregates have not borne this out. 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/or preventative treatments. In turn, that would eventually increase our ability to offset this devastating disease process and mitigate the suffering of LOAD patients and their loved ones.

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 and perceptions of patients as well as their family caregivers. 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 closer to the end of life than the beginning? What do patients and their family members think about this technology’s potential and applications?

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, and to examine their implications for society.

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.

Learn more about this project team by viewing the team's video.

Anticipated Outputs

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

Student Opportunities

Ideally, this project team will include 1-2 graduate students and 3-4 undergraduate students from a diverse set of disciplines such as neuroscience, biology, biomedical engineering, social sciences and humanities.

Students involved in bench research will gain the experience in cutting-edge genome and epigenome editing technologies using innovative human stem cell techniques. Students engaged in ethical, legal and social implications(ELSI) research will conduct primary data collection with health consumers and family caregivers and gain skills in developing a research protocol, conducting interviews, collecting data and conducting qualitative data analysis. Team members will contribute to publications, posters and abstracts and may also get the opportunity to participate and present their work at international Alzheimer’s and/or gene and cell therapy conferences. These experiences will provide them with learning opportunities to enrich their language skills.

Team interactions will include joint weekly team meetings that will alternate among student project presentations, journal clubs and external guest speakers. The team leaders will invite speakers to present on specific aspects of gene therapy, LOAD and ELSI and speak with the students about their career experiences.

The Summer 2021 component is required for all students and will take place over six weeks, from May 24 to July 2, 2021, for 40 hours per week.

Julio Barrera will serve as project manager.

Timing

Summer 2021 – Spring 2022 

  • Summer 2021:­­­ Receive training and practice lab safety; acquire skills in molecular techniques and laboratory procedures; search background literature; seek IRB approval; define ethical, legal and social questions; choose and launch individual projects (bench-based and caregivers survey); present on project aims, approaches and progress
  • Fall 2021: Continue individual research projects
  • Spring 2022: Continue individual research projects

Crediting 

Academic credit available for fall and spring semesters; summer funding available

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

 

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

Mouse model of Alzheimer's disease.

Team Leaders

  • Nathan Boucher, Sanford School of Public Policy
  • Ornit Chiba-Falek, School of Medicine-Neurology
  • Boris Kantor, School of Medicine-Neurobiology

/graduate Team Members

  • Suraj Dhulipalla, No Major Declared
  • Zollie Yavarow, Pharmacology-PHD

/undergraduate Team Members

  • Mohanapriya Cumaran, Biomedical Engineering (BSE)
  • Ishika Gupta, Psychology (BS)
  • Cordelia Hume
  • Lilly Kelemen, Neuroscience (BS)
  • Sahil Malhotra, Neuroscience (BS)
  • Suraj Upadhya, Biomedical Engineering (BSE)
  • Satya Yalamanchi

/yfaculty/staff Team Members

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