A CRISPR/Cas9 Based Therapeutic Strategy for Alzheimer's Disease

This project seeks to develop a therapy for Alzheimer’s disease by using novel genome editing CRISPR-based tools developed at UW-Madison. Alzheimer’s disease affects over five million people in the United States – well over 100,000 in Wisconsin alone – and is the only cause of death in the top 10 that cannot be prevented, cured, or slowed. In 2015, Alzheimer’s disease and other dementias cost the nation $226 billion, and given the increasing aging population, these numbers are expected to rise to a staggering $1.1 trillion by 2050. These figures profess the oncoming of a social and economic epidemic, underlining the desperate need for effective therapies that can slow or halt disease progression.

This project will use CRISPR/Cas9 technology to “cut and silence” pathologic proteins in Alzheimer’s disease, that should essentially block further progression of symptoms. CRISPRs – when combined with the enzyme Cas9 – are state of the art genome-editing tools that selectively cut portions of DNA. Such cutting often resulting in a truncated nonfunctioning molecule; and the goal here is to block the functionality of pathogenic proteins in Alzheimer’s disease. This project includes collaborating with bio-engineers to design cocoon-shaped nanoparticles designed to cross the blood-brain barrier and carry the CRISPR/Cas9 protein within their shell – delivering them within the brain.

This project holds promise for a ready application to Alzheimer’s disease. In principle, the overall “cut and silence” approach using CRISPR’s may also be applicable for other neurodegenerative diseases such as Parkinson’s disease, dementia with Lewy bodies, frontotemporal dementias, various other tauopathies and amyotrophic lateral sclerosis (ALS).

Principal Investigator

• Subhojit Roy
  Professor of Pathology
  

Co-Investigators

• Shaoqin Sarah Gong
  Professor of Biomedical Engineering
• Krishanu Saha
  Assistant Professor of Biomedical Engineering
  

Collaborators

• Anita Bhattacharyya
  Senior Scientist at Waisman Center
• William Murphy
  Professor of Biomedical Engineernig and Orthopedics
  
• Su-Chun Zhang
  Professor of Neuroscience and Neurology