Potential of antisense therapy for facioscapulohumeral muscular dystrophy

Abstract

Introduction: Facioscapulohumeral muscular dystrophy (FSHD) is an autosomal dominant genetic disorder characterized by progressive muscle degeneration. Currently, no effective treatment exists for the disease. Although the causative gene for FSHD, the double homeobox protein 4 (DUX4) gene, was identified over recent years, little effort has been made to develop targeted therapies. This is due to a lack of understanding of the gene and pathways involved. However, with the recent discovery that overexpression of myopathic DUX4 gene causes FSHD pathogenesis, inhibition of DUX4 and its downstream molecule has emerged as a promising therapeutic strategy against FSHD.Areas covered: In this paper we will discuss and review the latest research in the area of antisense knockdown therapy for FSHD, as well as a variety of accompanying issues, including efficacy and potential of antisense oligonucleotides.Expert opinion: Very recently, an effective antisense knockdown therapy targeting the paired-like homeodomain transcription factor 1 (PITX1) gene has demonstrated success in a newly developed mouse model. Similar to DUX4, PITX1 is specifically up-regulated in FSHD affected muscles. As such, the same knockdown principle using oligonucleotide could be applied to suppress the aberrantly expressed DUX4 and PITX1 in FSHD patients.