New FSHD mouse model treated with gene therapy

Published Date
Laura Jacobs
AAV virus

A recent study has demonstrated the value of a new mouse model of facioscapulohumeral muscular dystrophy (FSHD). Animal models are not only important for understanding muscle-wasting conditions, but also for studying the effects of potential treatments.

The mouse model was created by Dr Scott Harper and his team at Nationwide Children’s Hospital, Ohio, USA. Developing animal models of FSHD has proved difficult in the past because of the toxicity of the DUX4 protein. To overcome this, Dr Harper and his team used a genetic tool that allowed them to tightly control DUX4 levels in the mice.

Dr Harper said in a press release:

Even small amounts of ‘leaky’ production of DUX4 make it difficult to get the animals to develop properly. To produce the mice we wanted, we needed to control when and where DUX4 would be turned on in mice

The researchers found that when DUX4 was switched on, the mice developed a progressive muscular dystrophy. This shared features with human FSHD, therefore making the mice a valuable model for understanding the cause and progression of the condition.

The researchers also tested a gene therapy in the mice, to see if they would be a useful model for studying the effectiveness of potential treatments. This gene therapy was an adeno-associated virus (AAV) carrying a copy of the follistatin gene (see below).

The follistatin gene contains the instructions to make follistatin protein, a naturally-occurring protein that blocks myostatin. Blocking myostatin could potentially increase muscle mass and strength in people with muscle-wasting conditions, and there are now several researchers looking into this approach. The drug ACE-083, which is currently in clinical trials for FSHD, is a modified version of follistatin.

The follistatin gene therapy increased the size of the muscles that it was injected into, and also improved the strength of these muscles. Although this type of therapy doesn’t target DUX4, these results show that it still has a lot of potential for treating FSHD.

Follistatin has been shown to be safe when delivered to humans with other muscular dystrophies, such as Becker and Duchenne. While the effectiveness may be limited in those cases, because they are more aggressive, we think that the typically slower progression of FSHD may make it a better candidate for follistatin therapy. Although more work needs to be done, we believe our study shows that Follistatin gene therapy may prove to be a promising potential treatment for FSHD-associated muscle weakness.

said Dr Harper.

The study was published in the scientific journal, JCI Insight.

If you have any questions about this news story or any other FSHD research, please contact the MDUK Research Line on 020 7803 4813 or email

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