Applications of gene therapy for familial amyloidotic polyneuropathy

Abstract

Familial amyloidotic polyneuropathy (FAP), caused by mutated transthyretin (TTR), is the common form of hereditary generalised amyloidosis. As TTR is predominantly synthesised in the liver, liver transplantation is now considered an effective treatment for FAP to halt the production of variant TTR. However, this invasive therapy has several problems, leading to a requirement for a non-invasive treatment to be developed. At present, gene therapy for FAP has focused on two therapeutic strategies for suppressing variant TTR gene expression. The first is inhibition of variant TTR mRNA expression by antisense or ribozymes, and the other is the repair of mutated TTR gene by chimaeraplasts or single-stranded oligonucleotides. In particular, targeted gene repair is considered to be a promising tool for gene therapy because the effect can last permanently and the method is more suitable for proteins with a short plasma half-life. This article summarises the general concept of gene therapy and reviews the recent data on gene therapy for FAP.

• antisense
• chimaeraplasty
• familial amyloidotic polyneuropathy
• gene repair
• gene therapy
• ribozyme
• single-stranded oligonucleotides