Dean Burkin, professor of pharmacology and directory of cellular and molecular pharmacology and physiology graduate program at the University of Nevada School of Medicine in Reno, was awarded an MDA research grant totaling $300,000 over three years to test the effects of an existing FDA-approved drug on the function of heart and skeletal muscle in a mouse model of Duchenne muscular dystrophy (DMD).
Please describe your current research in DMD.
Duchenne muscular dystrophy is a fatal muscle disease caused by mutations in the DMD gene, which encodes for the muscle protein dystrophin. Dystrophin forms a molecular glue that binds muscle cells together and provides structural integrity. Loss of dystrophin in DMD causes progressive muscle weakness and results in premature death.
A second molecular glue, called the alpha7beta1 integrin, is also present in muscle and studies have shown in transgenic mouse models that increased levels of this protein can act as a surrogate for the absence of dystrophin and prevent disease progression.
In collaboration with the National Center for Advancing Translational Sciences (NCATS) at NIH, we conducted a muscle cell-based assay and screened over 400,000 compounds to identify alpha7beta1-enhancing drugs. We identified a novel compound, SU9516, that increases the alpha7beta1 integrin and prevents muscle disease in the mdx mouse model of DMD. This compound has an FDA-approved analog, and we now plan to test the effectiveness of this drug in mouse models of DMD.
Since this drug is already FDA-approved, successful outcomes of this study will develop the foundation for future clinical trials and more rapidly translate these studies into a novel class of integrin-based therapeutics for DMD.
What inspired you to study DMD?
As a scientist, I’m interested in understanding the role integrins and the extracellular matrix play in muscle development and disease. I’m inspired by the patients and families who live with rare genetic muscle diseases and who support MDA biomedical research to support scientists in their search to find treatments.
How will your research lead to treatments and cures?
If this study is successful then this information will contribute to IND enabling studies that will allow us to move this compound into clinical trials.
Why is it important that MDA continue to fund research in DMD?
MDA has outstanding support for biomedical research with a focus on therapy development for the muscular dystrophies. MDA also provides a critical bridge between basic research and clinical studies that allow therapeutics like ours to move forward towards clinical trials to help patients with neuromuscular disease.
What do you feel people impacted by DMD can have the most hope about with respect to research right now?
The preliminary preclinical studies are encouraging, and since this drug is already FDA-approved for another indication we believe that if this MDA-supported study is successful then we can rapidly move towards clinical trials. In addition, this would be the first alpha7beta1 integrin-enhancing compound. It’s a new class of drugs that can be used in combination with existing treatment options.
Does your work have any potential implications for other disease fields?
Yes, we have preliminary data to show this treatment may be effective in congenital muscular dystrophy.
To learn more about how MDA research is accelerating treatments and cures for DMD, visit mda.org.
Until Dec. 31, 2017 your support can mean twice as much — an anonymous group of generous donors has agreed to match every donation made, dollar for dollar, up to $100,000. Thanks in advance for your contributions.