PPMD Awards University of Florida $1 Million for Novel Gene Therapy Approach Targeting the Heart

The absence of dystrophin in the heart contributes to a progressive deterioration of cardiac muscle and eventual dilated cardiomyopathy (DCM) or heart disease.

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Tuesday, September 17, 2019 - 6:12pm
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Parent Project Muscular Dystrophy
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Key Points: 
  • The absence of dystrophin in the heart contributes to a progressive deterioration of cardiac muscle and eventual dilated cardiomyopathy (DCM) or heart disease.
  • Gene therapy, utilizing AAV vector as the delivery vehicle, provides a potential strategy to deliver transgenes targeting the mechanisms underlying the development of dilated cardiomyopathy.
  • This funding supports the development of a heart specific therapy using an AAV vector containing two transgenes to restore calcium handling and prevent mitochondrial dysfunction.
  • Chris and Patrick died of heart failure, so the heart is at the center of Duchenne for me.


PPMD Awards University of Florida $1 Million for Novel Gene Therapy Approach Targeting the Heart

HACKENSACK, N.J., Sept. 17, 2019 /PRNewswire/ -- Parent Project Muscular Dystrophy (PPMD), a nonprofit organization leading the fight to end Duchenne muscular dystrophy (Duchenne), announced plans to award H. Lee Sweeney, PhD, and his team at the University of Florida (Gainesville) $1 million to continue their exploration of developing novel therapies that can address the causes of dilated heart failure in Duchenne and Becker muscular dystrophy. This $1 million investment is part of PPMD's Cardiac Initiative and a direct result of the Duchenne community's generosity during the organization's 2018 end of the year campaign, as well as the support of other Duchenne families and foundations, including the Killian Family, Team Joseph, Another Day for Gray Foundation, and Small Heroes Foundation.

Parent Project Muscular Dystrophy logo. (PRNewsfoto/Parent Project Muscular Dystr...)

Duchenne is the most common fatal genetic disorder diagnosed in childhood, affecting approximately one in 5,000 live male births. Duchenne is caused by a change in the dystrophin gene. For people with Duchenne, cardiac disease is an area of great concern. The absence of dystrophin in the heart contributes to a progressive deterioration of cardiac muscle and eventual dilated cardiomyopathy (DCM) or heart disease.

Gene therapy, utilizing AAV vector as the delivery vehicle, provides a potential strategy to deliver transgenes targeting the mechanisms underlying the development of dilated cardiomyopathy. This funding supports the development of a heart specific therapy using an AAV vector containing two transgenes to restore calcium handling and prevent mitochondrial dysfunction. This therapy will potentially be able to treat the hearts of people living with Duchenne and Becker, in a way that is independent of, or complementary to, micro-dystrophin based gene therapy.

PPMD's Founding President and CEO, Pat Furlong, lost both of her sons to heart failure resulting from Duchenne, so this project is particularly meaningful to her and her family: "Heart issues don't just affect some people with Duchenne; they affect ALL people with Duchenne. And while we have improved cardiac care in Duchenne, we still need treatments that repair our children's hearts. Since our organization began 25 years ago, we have been asking questions and trying to better understand the effect of this disease on the heart.  Chris and Patrick died of heart failure, so the heart is at the center of Duchenne for me. That's why I am extremely proud to announce this $1 million investment into a gene therapy with the potential to heal the hearts of our loved ones. I am grateful to Dr. Sweeney and the amazing team at University of Florida, as well as the families in our community who believe in our mission and gave generously to help fund the fight to end Duchenne."

Dr. Sweeney, who has a long history in Duchenne research and has worked with PPMD for over two decades, says that PPMD's funding comes at a critical moment in the development of gene therapy: "These are exciting times for gene therapies – especially for gene therapies for Duchenne and Becker muscular dystrophy. However, while the current therapies may potentially help the skeletal muscles of patients, there is more to learn and to develop before we can be confident that we are doing all we can for the hearts of patients. The funds provided by PPMD will allow us to move faster toward the goal of creating the best possible gene therapy for the hearts of people with Duchenne and Becker."

Dilated cardiomyopathy (DCM) is the most common type of human cardiomyopathy, occurring mostly in adults 20 to 60. It affects the heart's ventricles and atria, the lower and upper chambers of the heart, respectively. Most forms of DCM are acquired forms from a number of causes that include coronary heart disease, heart attack, high blood pressure, diabetes, thyroid disease, viral hepatitis, and viral infections that inflame the heart muscle. In the case of certain forms of Becker, as well as in most cases of Duchenne, cardiomyopathy can ultimately limit the patient's survival.

While cardiomyopathy associated with Duchenne is technically a dilated cardiomyopathy that progresses to heart failure, many clinicians don't consider it a typical DCM because the patients' hearts don't tend to dilate until rather late in the disease progression. However, this is likely due to the fact that the hearts are not significantly burdened because of the patients' skeletal muscle disease and lack of ability to exercise.

Although Duchenne hearts do not dilate until late in disease progression, they get progressively stiff at earlier time points. This is clearly due to progressive fibrosis, and is slowed by the use of anti-fibrotic drugs, such as ACE inhibitors or ARBs (Angiotensin II Receptor Blockers). Interestingly, because of the fibrosis and lack of burden on the heart, the left ventricular chamber is actually smaller in diameter than normal after age 8 and until late in disease progression, when it begins to dilate.  Again, consistent with this being related to the fibrosis is the fact the individuals who were not given ACE inhibitors early in disease progression show the smallest ventricular diameters and progress the fastest once they begin to dilate.

In the case of Becker, there clearly is a subset of Becker patients that show a disproportionately rapid progression of their cardiac disease as compared to their skeletal muscle disease. This has called attention to the fact that there are some regions of the dystrophin molecule that are more important in the heart than they are in skeletal muscle, likely because of components that differ in importance or even in identity between the heart and skeletal muscle.further explore a novel gene therapy approach that will target the heart in people living with Duchenne and Becker muscular dystrophy. 

To learn more about PPMD's Cardiac Initiative, click here.

About Parent Project Muscular Dystrophy

Duchenne is a fatal genetic disorder that slowly robs people of their muscle strength. Parent Project Muscular Dystrophy (PPMD) is the largest most comprehensive nonprofit organization in the United States focused on finding a cure for Duchenne—our mission is to end Duchenne.

We demand optimal care standards and strive to ensure every family has access to expert healthcare providers, cutting edge treatments, and a community of support. We invest deeply in treatments for this generation of Duchenne patients and in research that will benefit future generations. Our advocacy efforts have secured hundreds of millions of dollars in funding and won two FDA approvals.

Everything we do—and everything we have done since our founding in 1994—helps those with Duchenne live longer, stronger lives. We will not rest until we end Duchenne for every single person affected by the disease. Join our fight against Duchenne at EndDuchenne.org and follow PPMD on Facebook, Twitter, and YouTube

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