New pharmacotherapies for genetic neuromuscular disorders: opportunities and challenges. Issue 8 (3rd August 2019)

• Record Type: Journal Article
• Authors: Ricci, Federica; Vacchetti, Martina; Brusa, Chiara; Vercelli, Liliana; Davico, Chiara; Vitiello, Benedetto; Mongini, Tiziana
• Is Part Of: Expert review of clinical pharmacology. Volume 12:Issue 8(2019)
• Page Start: 757
• Page End: 770
• Publication Date: 2019-08-03
• Subjects: Neuromuscular diseases -- molecular therapies -- genetic therapies -- gene therapy -- spinal muscular atrophy -- Duchenne muscular dystrophy -- Pompe disease -- X-linked myotubular myopathy -- myotonic dystrophy type 1; Clinical pharmacology -- Periodicals; 615.105
• DOI: 10.1080/17512433.2019.1634543
• Languages: English
• ISSNs: 1751-2433

Abstract

ABSTRACT: Introduction : Genetic neuromuscular diseases (NMDs) constitute a heterogeneous group of rare conditions, including some of the most disabling conditions in childhood. Recently, advanced technologies have greatly expanded preclinical and clinical research, and specific therapies have been developed. Area covered : We provide an overview of novel pharmacological approaches to the main NMDs, including Duchenne muscular dystrophy (DMD), spina muscular atrophy (SMA), X-linked myotubular myopathy, Pompe disease (PD), and myotonic dystrophy type 1, with attention to both achievements and unresolved therapeutic challenges. We conducted a selected review of relevant publications in the last five years identified through PubMed and Scopus. Additional information was derived from the website of clinicaltrials.gov and from the authors' direct knowledge of research activities. Expert Opinion : For the first time, targeted therapies have received conditional regulatory approval and have been introduced into clinical care: enzyme replacement therapy for PD, gene expression modulation for DMD and SMA, and gene therapy for SMA. Though not curative, these treatments can improve functioning and increase survival. Issues still to be addressed include: early recognition, definition of new emerging phenotypes, development of more sensitive outcome measures, long-term risk-benefit estimates, high costs sustainability, and criteria for therapy initiation and discontinuation.