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Cardiopulmonary phenotypic variability and discordance in Duchenne muscular dystrophy
  • David Birnkrant,
  • John Carter
David Birnkrant
MetroHealth Medical Center
Author Profile
John Carter
MetroHealth Medical Center
Author Profile

Abstract

Neuromuscular respiratory medicine has traditionally focused on mechanically assisted lung ventilation and mucus clearance. These therapies have prolonged survival for patients with Duchenne muscular dystrophy (DMD). However, the field is rapidly evolving in a new direction: it is being revolutionized by molecular and genetic therapies. A good correlation between a patient’s dystrophin mutation and his cardiopulmonary phenotype would allow accurate prediction of patient prognosis and would facilitate the design of studies that assess new DMD therapies. Instead, patient prognosis and the design of valid therapeutic studies are complicated by cardiopulmonary phenotypic discordance and variability, by which a notable proportion of DMD patients have unexpectedly good or poor cardiopulmonary function. The likely cause of phenotypic variability and discordance is genetic modifiers. Once the modifiers that affect cardiopulmonary function are better understood, it should be possible to create a personalized genetic profile that accurately predicts the prognosis of each individual DMD patient. This would allow investigators to assess the effect of new therapies in the context of each patient’s particular cardiopulmonary natural history. Amplification of beneficial cardiopulmonary genetic modifiers and blocking of detrimental modifiers is a promising strategy for creating new DMD therapies. When patients with chronic respiratory failure are treated with assisted ventilation, cardiac function determines their survival. Therefore, prioritizing new cardiac therapies is most likely to prolong patient survival. By focusing on these topics we aim to move neuromuscular respiratory medicine beyond assisted ventilation and coughing and into the age of translational medicine.

Peer review status:UNDER REVIEW

05 Aug 2020Submitted to Pediatric Pulmonology
06 Aug 2020Submission Checks Completed
06 Aug 2020Assigned to Editor
07 Aug 2020Reviewer(s) Assigned
01 Sep 2020Review(s) Completed, Editorial Evaluation Pending
27 Sep 20201st Revision Received
28 Sep 2020Submission Checks Completed
28 Sep 2020Assigned to Editor
28 Sep 2020Reviewer(s) Assigned