**Chapter 7 89**

Pharmacological Actions and Potential Therapeutic Use of Cannabinoids in Duchenne's Muscular Dystrophy *by Fabio Arturo Iannotti*

## **Section 5**


Preface

Skeletal muscle is a highly plastic organ that is modulated by various pathways controlling protein turnover. Loss of muscle is a serious consequence of many chronic diseases and of aging. Muscle loss is also common in muscular dystrophy, in which marked loss of various proteins such as the dystrophin–glycoprotein complex occurs around muscle fibers. The autophagy-dependent system and ubiquitin– proteasome signaling (UPS) are well known as major intracellular degradation systems, and their appropriate function is crucial to health and muscle homeostasis. Indeed, muscle wasting and weakness such as cachexia, dystrophy, and sarcopenia is characterized by marked decreases in protein content, muscle fiber size, and muscle strength. The apparent defect of autophagy-dependent signaling is

observed in various muscular dystrophies. The adaptive changes of UPS are highly controversial in Duchenne muscular dystrophy (DMD), limb-girdle muscular

Many researchers have investigated exercise-based, supplemental, pharmacological, gene therapy approaches to attenuate various muscular dystrophies. Currently, there is no cure for patients suffering from muscular dystrophies. Although several researchers actively try to determine the effect of pharmacological inhibition of myostatin for DMD patients, it is very difficult for obtaining positive effects and there are few possibilities of its clinical application. Glucocorticoids (GCs) are commonly used and still serve as a gold standard therapy. Nowadays, weekly, intermittent GC treatment has been shown to provide a better alternative to a daily regimen. More recently, attention has been paid to induced pluripotent stem cell technology and its potential application in DMD treatment, although almost all studies use DMD model mdx mice. In addition, the strategy using CRISPR/Cas9 technology progressed dramatically for the restoration of functional dystrophin. An increasing number of studies report successful and beneficial effects of CRISPR/ Cas9 only animal models of muscular dystrophy. Thus, it seems necessary that genome editing tools be applied the dystrophic patients for some time to come.

This book provides a comprehensive overview of the various muscular dystrophies, including characteristics, diagnosis, and classification. General treatment of drugs (e.g. corticosteroids) and physical therapy for muscular dystrophies are discussed. In addition, current applications for cell and tissue engineering using muscle stem cells or gene therapy are introduced. This book also deals with the recent advances in appropriate models of drug screening using cell cultures or mammalian organs in vitro in this field.

**Kunihiro Sakuma**

Tokyo Institute of Technology,

Professor

Tokyo, Japan

dystrophy, and Ullrich congenital muscular dystrophy.

Interspecies Translation: Bovine Marbling to Human Muscular Dystrophy *by Jose L. Valenzuela, Sally S. Lloyd, Edward J. Steele, Francis L. Mastaglia and Roger L. Dawkins*
