Promises and challenges in the diagnosis, translational research, and therapies for neuromuscular diseases in children and adolescents

Administrator: Sophelia HS Chan, Hong Kong

Dr. Yung Ohnmar 
Consultant Neurologist, Department of Neurology, University of Medicine1, Yangon, Myanmar 
Advances and challenges in the care of patients with neuromuscular disorders in a developing country - Myanmar 
Myanmar (Burma), famous for its natural beauty, is one of the countries with limitations on diagnostic and advanced therapeutic facilities. Recent advances in neuromuscular diseases (NMD) care started with the training opportunities for few neurologists attended overseas neuromuscular fellowship or workshops organized through collaboration with Asian faculties. Clinical diagnosis for common NMDs is now possible at clinics, and genetic diagnosis of selected patients can be achieved through overseas consultation. Currently facilities to support muscles biopsy and genetic testing for local people are lacking, and the disease-modifying medications are not available. The promises and challenges in the care of NMD patients in Myanmar will the current state of limited resources will be shared at the talk.

Dr. Gülçin Akıncı*, Prof. Haluk Aydın Topaloğlu
*Ass. Professor, Division of Pediatric Neurology, Behcet Uz Children's Hospital, Izmir, Turkey.
Professor of Pediatrics at Hacettepe University School of Medicine in Ankara, Turkey
Spinal Muscular Atrophy: A Therapeutics Update 
While the latest development of the three innovative therapies for Spinal Muscular Atrophy (SMA) which either act on SMN2 or replace SMN1 to increase its production of SMN protein, are not providing cures, they significantly improve the lifespan, motor function, breathing, and swallowing of symptomatic patients with SMA. The availability of newborn screening and early diagnosis has created an opportunity to prevent the disease development and lead to almost normal motor performance in pre-symptomatic patients treated early. The pros and cons of the three drugs focusing on efficacy, safety and early treatment, will be discussed.

Dr Sophelia HS Chan
Clinical Ass. Professor, Neurology Division of Department of Paediatrics and Adolescent Medicine, School of Clinical Medicine, LKS Faculty of Medicine, The University of Hong Kong
Dystrophinopathy - from bench to bedside and back to bench 
Dystrophinopathy are severe diseases caused by mutation of DMD gene leading to deficient dystrophin expression in the affected cells causing fatal cardiomyopathy, severe muscles weakness, and learning and behavioural disorders.  Dystrophinopathy features three phenotypic diseases -- Duchenne muscular dystrophy (DMD), Becker muscular dystrophy (BMD) and X-linked dilated cardiomyopathy (XLDCM). Currently, there is no cure for dystrophinopathy.   With the four approved disease-modifying drugs for DMD and ongoing clinical trials that bring on new hope, more transdisciplinary research is underway. Our challenge with DMD care and the use of patient-derived induced pluripotent stem cell disease model to study Dystrophinopathy, will be shared.

Dr Carsten Bönnemann 
Senior Investigator, Neuromuscular and Neurogenetic Disorders of Childhood Section, National Institute of Neurological Disorder and Stroke, National Institute of Health, USA 
Is there a path for transcript directed precision medicine?
Splice modulation using ASO (antisense oligonucleotides) are making inroads into the clinic for the treatment of neuromuscular disorders, with several FDA products (for DMD and SMA). At the same time, we find that next generation sequencing with in particular the incorporation of whole genome sequencing and RNAseq has led to increased recognition of pathogenic variants that affect splicing, some of which may be “actionable” using similar ASO based strategies. However, the number of patients with such a given variant will be very low, frequently just the single patient in whom the variant was found. What will it take to make precision medicines for few or even single patients with such actionable variants and bring them back to the patients who could stand to benefit from such a custom ASO as the ultimate rational drug design? Illustration with case studies, promises, and challenges will be discussed.