Treating Alzheimer’s and ATTR using CRISPR-Cas9 to target amyloidosis

Abstract

Approximately 50 million people live with Alzheimer’s (Alz) and 50,000 people are living with Transthyretin Amyloidosis (ATTR) worldwide. Both Alz and ATTR are types of amyloidosis, a disease where amyloid protein builds up in the body’s organs. Alz and ATTR are conditions with no known cures and similar etiologies but different manifestations in the brain and heart, respectively. Alzheimer’s disease is irreversible, which causes lifelong suffering for patients and their families. ATTR is a potentially fatal disease that causes heart problems for patients. Amyloidosis arises due to genetic mutations in the amyloid precursor protein (APP) or proteins involved in the generation of APP such as BACE1, PSEN1, PSEN2, APOE and transthyretin (TTR) genes, which result in the overexpression and accumulation of amyloid protein. CRISPR-Cas9 is a breakthrough gene editing technology that is capable of editing mutations in multiple genes with high specificity. This technology has the capability of treating both Alz and ATTR through targeted gene editing of the mutations that contribute to these diseases. This review will focus on BACE1, PSEN1, PSEN2, and APOE as targets for Alz and TTR as a treatment for ATTR through the use of CRISPR-Cas9. Various delivery mechanisms and current clinical trials will be discussed to identify the best delivery route of these treatments for the respective disease . A CRISPR-Cas9 derived treatment would bring new hope for patients with these diseases and could propel cures for other types of amyloidosis.