Targeted genetic therapies for inherited disorders that affect both cardiac and skeletal muscle.

Skeletal myopathies and ataxias with secondary cardiac involvement are complex, progressive and debilitating conditions. As life expectancy increases across these conditions, cardiac involvement often becomes more prominent. This highlights the need for targeted therapies that address these evolving cardiac pathologies. Musculopathies by and large lack cures that directly target the genetic basis of the diseases; however, as our understanding of the genetic causes of these conditions has evolved, it has become tractable to develop targeted therapies using biologics, to design precision approaches to target the primary genetic causes of these varied diseases. Using the examples of Duchenne muscular dystrophy, Friedreich ataxia and Pompe disease, we discuss how the genetic causes of such diseases derail diverse homeostatic, energetic and signalling pathways, which span multiple cellular systems in varied tissues across the body. We outline existing therapeutics and treatments in the context of emerging novel genetic approaches. We discuss the hurdles that the field must overcome to deliver targeted therapies across the many tissue types affected in primary myopathies. NEW FINDINGS: What is the topic of this review? Overlapping disease pathomechanisms and therapeutic opportunities in neuromuscular, skeletal and cardiac muscle diseases in the context of novel genetic therapies. What advances does it highlight? This review outlines the diverse genetic changes that drive pathomechanism across a set of neuromuscular conditions and highlight the emerging targeted biological therapies that are being developed to treat these conditions, with additional discussion of the hurdles to actualising genetically targeted precision medicine.