Scott Harper, associate professor of pediatrics at Ohio State University College of Medicine in Columbus, was awarded an MDA research grant totaling $300,000 for three years to test a gene therapy for facioscapulohumeral muscular dystrophy (FSHD).
Please describe your current research.
FSHD is caused by expression of the toxic DUX4 gene in muscle, and so strategies for treatments should focus on reducing or turning off DUX4. Before new treatments can be used in humans, they must first be tested in animal models to ensure that they (1) work and (2) are safe. In the case of FSHD, this would ideally mean having an animal model that expresses DUX4 and has diseased muscles, which could then be treated with an anti-DUX4 therapy.
Although mice have been created that contain the DUX4 gene in their chromosomes, they unfortunately do not develop muscle disease or they die before birth. This fact represents a roadblock for therapy development. We have recently developed such a mouse, and with this grant we will characterize it and use it for DUX4 inhibition therapy testing.
What inspired you to study FSHD?
As a graduate student, I worked on Duchenne muscular dystrophy and gene therapy. As a postdoctoral fellow, I gained expertise in gene silencing approaches for treating dominant genetic diseases. In particular, I was developing potential treatments for Huntington’s Disease, a brain disorder.
When I started my own lab nine years ago, I realized there wasn’t a lot of work being done to tackle dominant muscular dystrophies, and I saw an opportunity to apply my two areas of training — in muscle gene therapy and gene silencing approaches — to develop a new research program focused on therapy. Around that time, the FSHD field was gaining momentum toward understanding the root causes of the disease, and I began working on FSHD with the idea that our gene silencing therapies could be a promising strategy to treat it. We haven’t changed course since.
What is your focus in the field of FSHD research and why is it important?
We have been working on developing DUX4-expressing models of FSHD as well as anti-DUX4 therapies.
FSHD is an important disease, and in my opinion, it has been understudied and underfunded for too long. This is changing now, but compared to research on other muscle disease, I think we still have some ground to make up. There are a lot of people out there waiting for a treatment, and I think it’s important that researchers in the field continue working hard to deliver something.
How will your research lead to treatments and cures?
We will provide a well-characterized mouse model of FSHD that we will distribute to the field. Moreover, we hope that this model will be useful for testing therapies that can be brought forward toward the clinic.
What do you feel people impacted by FSHD can have the most hope about with respect to research right now?
Ten years ago, there was no consensus on the underlying causes of FSHD, we didn’t have validated models that expressed the DUX4 gene, and there were no targeted treatments under development. Today, thanks to the work of many researchers, we better understand the underlying causes, we have a gene target (DUX4), we have animal and cell models, and there are numerous treatment strategies in the pipeline. The FSHD field has made a significant amount of progress during the last decade. Still, there’s a lot we still don’t know and we need to keep up the momentum.
Does your work have any potential implications for other disease fields?
Yes. The gene silencing strategies we are developing are applicable to virtually all dominantly inherited muscular dystrophies. They would have to be modified to target other genes, but the principles are the same.
To learn more about how you can #EndFSHDwithMDA, visit mda.org.
