What are the aims of this research project?
The primary objective of this project is to develop molecular patches that can prevent the production of toxic DUX4 protein that causes facioscapulohumeral muscular dystrophy (FSHD). The molecular patches will be linked to short protein fragments called peptides. These peptides help the molecular patches to get inside cells, thus improving their delivery into muscles.
Several peptide-linked molecular patches will be designed and optimised using computer modelling software. They will then be tested in cells grown in the laboratory that originated from a person with FSHD. The researchers will assess how effective each peptide-linked molecular patch is by measuring the amount of DUX4 protein in the cells.
The most effective peptide-linked molecular patches will then be injected into FSHD mouse models. The researchers will measure the amount of DUX4 protein in the mouse muscles, in addition to other proteins that are thought to be associated with the condition. They will test various doses of the peptide-linked molecular patches, and over extended periods of time, which will help to ensure that the best one is taken forward for further development.
Why is this research important?
Currently there is no effective treatment for FSHD because of its complex genetics. There are many factors that influence the expression of the toxic DUX4 protein, making it hard to pinpoint one particular factor to target. This research could be an important step towards a treatment that addresses the genetic cause of the condition.
Although molecular patches are currently in clinical trial for Duchenne muscular dystrophy, there are problems associated with the delivery of the molecular patches to muscles and other target organs. This project will address this by linking the molecular patches to peptides. Enhancing the technology in this way could lead to better therapeutic outcomes.
How will the outcomes of this research benefit people with FSHD?
This research could lead to the development of a new treatment that has the potential to reverse, stabilise or at least slow the progression of muscle weakness in people with FSHD.
How might this research impact on other neuromuscular conditions?
Molecular patches have the potential to treat the underlying genetic causes of a range of muscle-wasting conditions. This project will enhance molecular patch technology so that it can target muscles effectively and efficiently, which will be helpful for designing molecular patches for other neuromuscular conditions.
Project leader: Dr Linda Popplewell
Institute: Royal Holloway, University of London
Condition: Facioscapulohumeral muscular dystrophy
Duration: three years, starting 2016
Total cost: £218,450
Official title: Development of cell-penetrating peptide conjugated antisense oligonucleotides for the treatment of facioscapulohumeral muscular dystrophy
Read our factsheet on FSHD
Find out what other FSHD research projects we are funding
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