David Birnkrant, MD
Professor of Pediatrics, Case Western Reserve University School of Medicine
Director of Pediatric Pulmonology & Student Education, MetroHealth Medical Center
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: This study updates guidance on all aspects of the multi-disciplinary care of patients with Duchenne muscular dystrophy (DMD). The project was funded by the CDC’s National Center on Birth Defects and Developmental Disabilities and the results were recently published as three articles in The Lancet Neurology. The project was guided by a 25-member steering committee. Eleven expert committees worked over a period of three years to develop guidelines based on the RAND/UCLA appropriateness method, in which assessments and interventions were evaluated for appropriateness and necessity. The recommendations update those originally published in 2010.
Duchenne muscular dystrophy is transmitted by X-linked recessive inheritance and thus affects primarily boys and men. Patients affected by DMD do not produce functional dystrophin protein, resulting in progressive weakness of skeletal, respiratory, and heart muscles, causing a shortened life span. Teens and young men may require surgery for curvature of the spine, a ventilator device to assist breathing, and a feeding tube to help ensure adequate nutrition. The approach of the various subspecialties involved in DMD management has evolved, with more anticipatory assessment and therapy, identifying and addressing predictable medical complications as early as possible for optimal patient outcomes. With this kind of multi-disciplinary care, people with DMD now live into their 30s and beyond.
Along with the emergence of new genetic and molecular therapies, the recognition that people with DMD are living longer was one of the main motivations behind the need for these updated care considerations. Patients with DMD, their families and their advocacy organizations are driving a new emphasis on optimizing quality of life, not just prolongation of survival. Thus, there was a need to address issues related to transitions of care from childhood to adulthood, coordination of care across subspecialties, and other topics related to education, vocation, independence, personal relationships, emotional health, and intimacy. The updated care considerations thus include eleven topic areas, eight of which were part of the 2010 guidelines.
These are: (1) diagnosis, (2) neuromuscular management, (3) rehabilitation management, (4) gastrointestinal and nutritional management, (5) respiratory management, (6) cardiac management, (7) orthopedic and surgical management, and (8) psychosocial management. Three topics are new: (9) primary care and emergency management, (10) endocrine management (including growth, puberty, adrenal insufficiency, and bone health), and (11) transitions of care across the lifespan.
MedicalResearch.com: What should readers take away from your report?
Response: This is an exciting time to be involved in the care of people with Duchenne muscular dystrophy. Contemporary management by the key specialties has been highly successful, with tangible improvements in survival, and multi-disciplinary care continues to evolve. More is known about the benefits and limitations of glucocorticoids, the current mainstay of pharmacologic therapy and new therapies are becoming available that could transform the field, including therapies that can treat the underlying genetic defect, rather than just compensate for the disease’s medical complications. However, DMD is a very severe, multi-system illness and many challenges remain. It will be critical for patients, their families, and their advocacy organizations to continue their integral role in guiding the future of DMD care so that patients can achieve their personal goals for quality of life, not just duration of survival.
MedicalResearch.com:What recommendations do you have for future research as a result of this study?
Response:The articles in The Lancet Neurology include an overview of future directions in the field. Additionally, a group of follow-up specialty articles is currently in review at the journal Pediatrics; those articles will discuss future research in more detail. Globally, development of the new genetic and molecular therapies is key. Important questions include: which strategies will prove to be most successful (e.g., exon skipping, viral-mediated microdystrophin gene replacement, anti-inflammatory therapy, and/or upregulation of proteins like utrophin, that function similarly to dystrophin)? At what age and in which patients will these therapies work best? How do we integrate proven therapy, especially glucocorticoids, into new therapeutic protocols? Can new therapies be customized to each patient’s particular genetic profile? While the new genetic and molecular therapies tend to get the most attention, at a more “granular” level, each of the specialties involved in . Duchenne muscular dystrophy care has its own list of areas that need more research. For example, technological advances, such as robotics, have the potential to transform rehabilitation medicine. Newborn screening for DMD may become a reality, if it can be shown that initiating therapy during infancy benefits patient outcomes. DMD-specific growth charts and body composition analysis could guide better nutritional strategies. With wide adoption of noninvasive ventilation to compensate for respiratory failure, DMD cardiomyopathy and resulting heart failure have become the main causes of patient mortality. Thus, newer pharmacologic and device therapies are needed to improve cardiac outcomes. There is a critical need to create a medical, social and financial infrastructure for transitions to adulthood that includes continuity of DMD-centered healthcare and a focus on quality of life. Patients and families need better access to palliative and end-of-life care. Another broad area is the need to develop clinically meaningful outcome measures within each subspecialty in order to assess the effectiveness of the new DMD therapies. In this context, one of my own interests is the prevalence of cardiopulmonary phenotypic variability in patients with Duchenne muscular dystrophy. Our initial observations suggest that the dystrophin genotype does not reliably predict cardiopulmonary function in a significant proportion of DMD patients and that heart and lung function is frequently discordant. For example, prolonged survivors of DMD often had poor lung function but surprisingly good heart function, despite their advanced age. Thus, a patient’s prolonged survival might be attributed to a new therapy when the actual explanation is the patient’s unexpectedly favorable cardiac phenotype.Disclosures: Funding was provided under the Muscular Dystrophy Care and Treatment Act. Dr. Birnkrant has issued patents and patent applications that relate to respiratory devices. Detailed disclosures are contained in the articles.