Compensatory Plasticity of Breathing in Patients with Neuromuscular Disease

Neuromuscular diseases are comprised of variable, often inherited conditions and characterized by muscular (e.g. Duchenne muscular dystrophy), neural (e.g. amyotrophic lateral sclerosis) or a mixed neuromuscular (e.g. Pompe disease) dysfunction. While individual neuromuscular disorders differ in the underlying mechanism and exhibit a unique disease presentation, the consistently leading cause of morbidity and mortality is respiratory failure. Loss of breathing function is literally a “life‐or‐death" issue for patients. Clinical management of breathing relies upon pulmonary function tests to estimate the degree of respiratory involvement in patients, but standard pulmonary function test results can be biased by learning, cognition, or poor effort. This presentation will discuss compensatory neuromuscular adaptations to preserve breathing in the face of worsening disease, including changes in neural drive, neuromuscular junction plasticity, and a greater reliance on less‐affected respiratory motor pools. Detection of these adaptations is needed for prescribing supportive therapies with greater precision and identifying clinically meaningful changes in response to treatments. Citing natural history studies from our team and others, this presentation will feature clinical approaches to objectively evaluate respiratory motor control and gain mechanistic insights into neuromuscular disease. The control of breathing will then be discussed in the context of clinical trials, with an emphasis on current and emerging treatments directed toward improvements in ventilation. Examples will highlight basic‐clinical collaborations that promote new therapeutic frontiers for patients with neuromuscular disease. Support or Funding Information This work is supported by National Institutes of Health awards R21 HD090752 and U01 HL121842.