**Author details**

Tatsushi Mutoh1,2\*, Tomoko Mutoh2 , Yasuyuki Taki2 and Tatsuya Ishikawa1

\*Address all correspondence to: tmutoh@tiara.ocn.ne.jp

1 Research Institute for Brain and Blood Vessels-AKITA, Akita, Japan

2 Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

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The authors gratefully acknowledge the financial support of Grants: Grant-in-Aid for Scientific Research from the Japan Society for the Promotion of Science (15K10966) and Life Science

, Yasuyuki Taki2

2 Institute of Development, Aging and Cancer, Tohoku University, Sendai, Japan

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#### **Advanced Treatments and Emerging Therapies for Dystrophin-Deficient Cardiomyopathies Advanced Treatments and Emerging Therapies for Dystrophin-Deficient Cardiomyopathies**

Jordi Camps, Enrico Pozzo, Tristan Pulinckx, Robin Duelen and Maurilio Sampaolesi Jordi Camps, Enrico Pozzo, Tristan Pulinckx, Robin Duelen and Maurilio Sampaolesi

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65061

#### **Abstract**

Dystrophinopathies are characterized by skeletal and cardiac muscle complications because of a lack or shortened DYSTROPHIN protein. Ventilation assistance and corticosteroid treatment have positively affected life outcome but lead to an increased incidence of cardiomyopathy. Cardiomyopathy is now the leading cause of death in patients with dystrophinopathy. Thus, coherent guidelines for cardiac care have become essential and need to be communicated well. Progression of cardiac complications in patients with dystrophinopathy diverges from standard dilated cardiomyopathy development and monitoring and medical care for dystrophinopathy. This chapter summarizes current guidelines and recommendations for monitoring and clinical treatment of cardiac complications in patients with dystrophinopathy and provides a thorough survey of emerging therapies focusing on cardiac outcomes.

**Keywords:** dystrophin, Duchenne and Becker muscular dystrophy, dilated cardiomy‐ opathy, symptomatic treatment, exon skipping, gene and cell therapy

### **1. Introduction**

Dystrophinopathies are agroupofdiseases comprisingDuchennemusculardystrophy(DMD), Becker muscular dystrophy (BMD) and X‐linked dilated cardiomyopathy (XLDCM), charac‐ terized by a shortened or absent *DYSTROPHIN* gene. DMD is the most prominent, with an incidence around 1:5000 live male births [1]. BMD occurs about three times less than DMD [2], while XLDCM is extremely rare [3]. *DYSTROPHIN*—part of the dystrophin‐glycoprotein complex (Appendix 1)—is locatedontheXchromosome, andtherefore, onlymales are affected.

© 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2017 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

The main clinical feature of patients with dystrophinopathy is an early loss of ambulation depending on the availability of DYSTROPHIN. Patients with DMD completely lack DYS‐ TROPHIN—the pathological mechanisms are discussed in Appendix 2—and are presented with the most severe disease progression. This is indicated by a loss of ambulation around 10 years of age and consequent ventilation assistance, followed by death during the second or third decade [4]. Conversely, patients with BMD still express a truncated form of DYSTRO‐ PHIN. Although only partially functional, this still has an effect on disease progression and life expectancy, which are drastically prolonged [5]. Patients with XLDCM show the absence of DYSTROPHIN in the heart, while expression in skeletal muscles is conserved. Several hypotheses have been proposed for this peculiar genotype [3]. In patients with dystrophin‐ opathy, the routine use of corticosteroids and nocturnal ventilation support have dramatically improved the life expectancy and its quality. Unfortunately, this brings up other complications, as the incidence of cardiomyopathy is raising and is nearly ubiquitous in older patients with DMD. In this perspective, monitoring and treatment of cardiac complications becomes more and more important.

This chapter contains an overview of the current monitoring and treatment guidelines and state‐of‐the‐art therapies for dystrophin‐deficient cardiomyopathies. The clinical features of dystrophinopathies with an emphasis on cardiac disease progression will be discussed briefly, followed by a description of the diagnostic process and current management strategies. Conclusions from recent clinical trials on current symptomatic treatments will be summarized and emerging therapies will be discussed in detail, from promising preclinical research to ongoing clinical trials.
