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

Background

The causative factors and the mechanism behind the onset and progression of Alzheimer’s disease remain unknown. Historically, the common view has been that the A-beta peptide is the principal cause, but multiple clinical trials targeting the A-beta aggregates have not proved this theory. Moreover, it’s thought that treating Alzheimer’s disease at a late stage, when the damage to the patient is already apparent, would diminish the effectiveness of the disease-modifying therapy.

Gaining insight into the biological pathways and molecular basis underlying Alzheimer’s disease should lead to the development of disease-modifying and preventative treatments. Such treatments will increase our ability to offset this devastating disease and mitigate the suffering of Alzheimer’s disease patients and their loved ones. That said, new therapies bring new questions. How will gene therapy in Alzheimer’s disease 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 Bass Connections project will advance development of new gene therapy technologies that will target age-related brain diseases such as Alzheimer’s disease. Students will conduct research on Alzheimer’s disease etiology and mechanisms using cutting-edge genome editing technologies and state-of-the-art stem cell techniques.

By conducting hands-on research and working with knowledgeable mentors, team members will gain real-world experience in developing gene therapies aimed at addressing a devastating public health problem. The outcomes of this research will greatly facilitate the development of next-generation “smart” drugs for treating Alzheimer’s disease.

To examine the ethical, legal and social issues of Alzheimer’s disease treatment, team members will undertake case studies of earlier gene therapies and trace their development and deployment; 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 palliative care/quality-of-life issues.

Anticipated Outputs

Manuscripts in scientific journals; presentations at professional conferences; external grant applications; independent projects

Student Opportunities

Ideally, the team will include 3-4 undergraduates and 1 graduate student from both the sciences and the humanities, provided they have an abiding interest in the science of neurodegenerative diseases and the ethical, legal and social issues raised by gene therapy for such diseases.

Team members will have weekly meetings that will alternate among student project presentations, journal clubs and external guest speakers. Guest speakers will present on specific aspects of Alzheimer’s disease, such as clinical research, caregiving of patients, pathology and postmortem examinations, ethical and legal aspects related to age-related health and gene editing. In addition, students will present papers of interest related to their individual projects.

Students will participate in laboratory experiments and will master a variety of lab techniques, ranging from basic molecular biology techniques to more cutting-edge methods. They will also acquire the skills and tools for designing a research study. In addition, students will investigate ethical, legal and social questions related to gene therapy for Alzheimer’s disease and other late-onset neurodegenerative conditions. Team members will acquire skills in searching the literature, collecting supporting evidence and compiling and interpreting case studies.

For all individual projects, students will develop their research questions, design strategies and choose methods to analyze their data and interpret results. All students will take independent studies for the fall semester to work on their individual research projects. In addition, team members will contribute to publications, posters and meeting abstracts. Selected students may also get the opportunity to participate in international Alzheimer’s conferences.

The Summer 2019 component is obligatory. It will run from May 28, 2019, to August 2, 2019 (10 weeks).

Timing

Summer 2019 – Spring 2020

  • Summer 2019: Acquire skills in techniques and laboratory procedures; search literature and define relevant ethical, legal and social questions; initiate individual projects that could potentially become the subjects of independent studies in fall and spring semesters
  • Fall 2019: Independent study
  • Spring 2020: Independent study

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

Crediting

Independent study credit available for fall and spring semesters; summer funding available

 

Image: Human iPSC-derived neurons for screening next-generation gene therapy strategies in Alzheimer’s

Human iPSC-derived neurons for screening next-generation gene therapy strategies in Alzheimer’s

/faculty/staff Team Members

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