Current and emerging treatment strategies for Duchenne muscular dystrophy

Figures & data

Figure 1 A young boy illustrates the typical Gowers’ sign.

Notes: The maneuver consists of pushing on the floor, followed by climbing up on his legs to achieve a standing position, due to proximal muscle weakness.

Table 1 Current supportive strategies for DMD

Key stages and strategies	Early to late ambulatory stage (4–9 years old)	Early nonambulatory stage (10–16 years old)	Late nonambulatory stage (>16 years old)
Family knowledge: Show respect for the family’s perspective and expertise Identify family’s needs, strengths, and priorities on an ongoing Basis Provide information that matches the family’s needs Facilitate family-to-family support	Discuss: DMD natural history Role of corticosteroids Genetic counseling Carrier testing if indicated Provide written material, websites, and peer support information Participation in DMD research Parent project website MDA	Discuss: Review previous topics Nutrition, scoliosis, cardiac, respiratory issues, and corticosteroids-related side effects Management of nocturnal hypoventilation and cardiomyopathy if present School and social support Respite and financial needs Adolescent quality of life	Discuss: Review previous topics Home care Cardiac treatment Nutritional support Options for long-term ventilation support Transition to adult services Advance care directive
Professional support: Involve families in decision-Making Develop services that are flexible to the needs of individual families Provide service coordination and integration within and between sectors	Medical consultations: Genetics Respirology Orthopedics Cardiology Neurology Pediatrics Physiatry Ophthalmology Allied health support: Clinic Nurse, Dietitian Physiotherapy, Psychologist Social work, Occupational therapy MDA community liaison	Medical consultations: As before, plus: Endocrinology for osteoporosis and bisphosphonate therapy Home care Chest physiotherapy Lung volume recruitment Cough assist devices Seating for wheelchair Passive and active exercises	Medical consultations: As before, plus: Palliative care
Medical therapy: Provide high-quality general and illness-specific information Establish opportunities for family involvement in decision-making at all levels of the organization	Immunizations: Varicella vaccine Pneumococcal vaccine Influenza vaccine Corticosteroids: Deflazacort (0.9 mg/kg/d) or prednisone (0.75 mg/kg/d) Physiotherapy: Passive stretching, night splints Bone health: Calcium supplementation Vitamin D supplementation Others: Behavioral intervention Weight management	Review previous topics, plus: Interventions (as required): ACE inhibitor, diuretics, and/or beta-blocker for cardiomyopathy Antibiotics for respiratory tract infections Sitting ankle–foot orthotics Scoliosis surgery Pre-op consultations: Cardiology Respirology Anesthesiology	Review previous topics
Clinical/laboratory monitoring: Create family-friendly physical environments	Weight, height Blood pressure Muscle function testing ECG, echocardiogram Pulmonary function testing Spine X-ray Wrist X-ray for bone age Bone densitometry scan 25-hydroxyvitamin D level	Same as before, plus: Sleep studies ECG, echocardiogram (yearly)	Same as before

Note: Copyright © 2010. Cambridge University Press. Adapted from McMillan HJ, Campbell C, Mah JK. Canadian Paediatric Neuromuscular Group. Duchenne muscular dystrophy: Canadian paediatric neuromuscular physicians survey. Can J Neurol Sci. 2010;37(2):195–205.³³

Abbreviations: DMD, Duchenne muscular dystrophy; MDA, muscular dystrophy association; ACE, angiotensin-converting enzyme; ECG, electrocardiography.

Table 2 Emerging therapies for DMD

Gene replacement therapies

rAAV2.5-CMV-Mini-dystrophy

rAAVrh74.MCK. Mini-dystrophya

rAAV1.CMV.huFollistatin344a

Other genetic therapies

Nonsense suppression

Gentamicin

Ataluren (Translarna)a

NPC-14 (arbekacin sulfate)a

Exon skipping

Exon 53

SRP4053 (Serapta)a

PRO053 (Prosensa)a

NS-065/NCNP-01a

Exon 51

AVI-4658/eteplirsena

GSK2402968/drisapersena

Exon 45

DS-5141ba

PRO045a

SRP4045a

Exon 44

PRO044a

Cell therapy using muscle precursor cells or stem cells

Myoblasts transfera

Mesoangioblasts transplantation

Umbilical cord based allogenic mesenchymal stem cellsa

Bone marrow autologousa and mononuclear stem cellsa

Membrane stabilization and upregulation of cytoskeletal proteins

Utrophin upregulation: SMT C1100

Treatment of secondary cascades

Anti-inflammatory drugs

Givinostat (HDAC inhibitor)a

CAT-1004 (NF-κB inhibitor)a

Flavocoxid

TAS-205 (PDGD2 synthase inhibitor)

Others: idebenone, pentoxifylline, coenzyme Q10, oxatomide

Antifibrotic drugs/transforming growth factor beta (TGF-β) inhibitors

Losartan and lisinopril

HT-100 (halofuginone)a

FG-3019 (monocloncal antibody to CTGF)a

Muscle regeneration

Myostatin inhibitors: ACE-031, PF-06252616a, BMS-986089a

Insulin growth factor (IGF1)a

Treatment of muscle ischemia

Phosphodiesterase 5 (PDE5) inhibitors: tadalafil and sildenafil

VEGF

Notes:

a Active or ongoing clinical trials, accessed on February 18, 2016 from www.clinicaltrials.gov.

Abbreviations: DMD, Duchenne muscular dystrophy; NF-κB, nuclear factor-kappa B; TGF-β, transforming growth factor beta; CTGF, connective tissue growth factor; ACE, angiotensin-converting enzyme; IGF, insulin growth factor; PDE5, phosphodiesterase 5; VEGF, vascular endothelial growth factor.

McMillanHJCampbellCMahJKCanadian Paediatric Neuromuscular GroupDuchenne muscular dystrophy: Canadian paediatric neuromuscular physicians surveyCan J Neurol Sci201037219520520437929

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