Developing LNA-based therapy for FSHD

Budget

• Amount Awarded: $179,104 for two years
• FSHD Canada Foundation Contribution: US$20,000
• Date Awarded:04/01/2017
• End Date: 03/31/2019

Lay Abstract

Investigators:
• Yi-Wen Chen Children’s National Health System (Washington DC)
• Toshifumi Yokota University of Alberta Faculty of Medicine and Dentistry (Alberta, Canada)

Yi-Wen Chen and Toshifumi Yokota are investigating one of the most promising antisense oligonucleotides (AON) compounds called LNA (locked nucleic acid) gapmer for its efficacy in reducing DUX4 in cell culture and in a mouse model of FSHD. AONs are short gene-like molecules that bind to and inactivate target genes (in this case DUX4). LNA gapmers are a “third generation” AON designed to overcome some problems that made earlier AONs unsuitable for use as therapeutics. LNA gapmers are more stable, resistant to being degraded, and can penetrate the cell membrane and get into cell nuclei where the target DUX4 gene resides. Dr. Yokota will continue to improve the anti-DUX4 LNA gapmer, testing them in FSHD cell lines, while Dr. Chen will test the safety and efficacy of the molecules in a mouse model of FSHD.