Muscle biopsies in clinical trials for Duchenne muscular dystrophy – Patients’ and caregivers’ perspective

Ingrid E.C Verhaart,Alex Johnson,Sejal Thakrar,Elizabeth Vroom,Fernanda De Angelis,Francesco Muntoni,Annemieke M Aartsma-Rus,Erik H Niks

doi:10.1016/j.nmd.2019.06.004

Abstract

The number of clinical trials for Duchenne muscular dystrophy is increasing. Many trials require muscle biopsies, which involve an invasive surgical procedure. Little is known about short- and long-term impacts of muscle biopsies as perceived by patients and caregivers. Therefore a survey was held among patients and their caregivers who participated in trials involving muscle biopsies, in seven countries. Seventy-eight responses were received. Analysis revealed that many patients and parents had significant anxiety before the biopsy. The main concern of caregivers was the required general anaesthesia. In most cases biopsies caused pain and temporarily hampered daily activities. The main long-term impact was scarring, although large variation in size was reported. Seventy-nine percent of caregivers were little bothered and 21% were moderately or severely bothered by the scar. Willingness to consider another biopsy in future protocols was higher for open-label studies than for placebo-controlled trials. Caregivers stressed the importance of knowing the results of biopsy analyses; only a minority actually received this information. Recommendations are made on the informed consent procedure regarding risks and consequences of muscle biopsies, and communication of results. Furthermore, efforts should be made to minimise the impact of biopsies through pain management and by considering plastic surgery.

Highlights

Duchenne muscular dystrophy (DMD) is a devastating disorder hallmarked by progressive muscle weakness leading to loss of ambulation in childhood, respiratory insufficiency, cardiomyopathy and early death [1]
It consisted of three parts: 1) General characteristics of the patient, which clinical trial they had participated in, the number and location of the biopsies taken as defined in the study protocol, and if general or local anaesthesia had been used; 2) Perception of the child about the biopsy; 3) Perception of the parent/caregiver about the biopsy
Over the last years a significant progress has been made in the development of therapies for DMD

Summary

Introduction

Duchenne muscular dystrophy (DMD) is a devastating disorder hallmarked by progressive muscle weakness leading to loss of ambulation in childhood, respiratory insufficiency, cardiomyopathy and early death [1]. Mutations in the DMD gene lead to absence of the dystrophin protein that normally links the extracellular matrix to the contractile elements in the sarcolemma, which is thought to protect skeletal muscle. Thakrar et al / Neuromuscular Disorders 29 (2019) 576–584 disrupted reading frame through exon skipping of pre-mRNA transcripts, and delivery of micro-dystrophins using adenoassociated viral vectors. Other therapeutic approaches aim to increase levels of utrophin, a protein with similar properties as dystrophin, to reduce the levels of myostatin, an inhibitor of muscle growth, in order to increase muscle mass, or to use histone deacetylase (HDAC) inhibitors to simultaneously boost muscle regenerative capacity, and reduce inflammation and fibrosis formation [4]

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