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Notice of Special Interest (NOSI): Respiratory Complications of the Muscular Dystrophies (R01)

National Institutes of Health

The purpose of this NOSI is to encourage research grant applications focused on respiratory complications of the muscular dystrophies . This includes further elucidation of respiratory phenotypes in humans; research to optimize pulmonary function testing and existing respiratory therapies in humans; and mechanistic and translational research, including in vitro and in animal models, that examines respiratory muscle response to gene therapies and other therapeutic strategies in the muscular dystrophies.

Muscular dystrophies are a heterogenous group of inherited muscular diseases that include Duchenne muscular dystrophy (DMD), facioscapulohumeral muscular dystrophy, myotonic dystrophy, limb-girdle muscular dystrophies, congenital muscular dystrophies and other types of muscular dystrophy, all of which invariably lead to progressive weakness and respiratory decline. Advances in clinical pulmonary care have delayed the onset of respiratory failure and increased the life span in some of these conditions like DMD. However, acute respiratory failure from pneumonia, aspiration events, Acute Respiratory Distress Syndrome (ARDS) with prolonged stays in the intensive care unit, and chronic respiratory insufficiency with need for invasive and non-invasive support remain some of the leading causes of mortality and morbidity in affected individuals. Cardiopulmonary interactions in the context of the progressive obstructive and/or restrictive respiratory disorders in these conditions also need elucidation.

This NOSI calls for detailed respiratory phenotyping to elucidate the trajectory, early biomarkers, and outcome measures of decline in respiratory function to facilitate early intervention, which has been shown to delay mortality and significantly improve Health Related Quality of Life (HRQOL). Additionally, research on optimizing prediction and quantification metrics of the impact of existing interventions on pulmonary function is considered responsive to this NOSI. Also encouraged are studies that are aimed at optimizing pulmonary function testing to better address physiological variations in the different dystrophies related to upper airway obstruction due to weakness (both when awake and during sleep); research on early diagnosis of obstructive and restrictive lung disease in the setting of increased thoracic compliance and decreased elastic recoil; and investigations to understand inspiratory strength training and its role in improving pulmonary function.

This NOSI is a call for research that will address barriers to participation in research in NIH-designated populations that experience health disparities and/or other understudied populations in the muscular dystrophies by employing strategies and resources to reduce obstacles and encourage outreach to these populations living with muscular dystrophies, as described in the website, https://www.mdcc.nih.gov/strategies-promote-diversity-muscular-dystrophy-research-participation . To enhance awareness and participation in research among understudied population, resources built by NIH-wide Community Engagement Alliance ( CEAL ) against COVID-19 disparities could also be leveraged by investigators in the muscular dystrophy space, building upon proven strategies.

This NOSI also encourages research to better characterize respiratory consequences of targeted experimental gene therapy to respiratory muscles in animal models. A better understanding of respiratory implications would guide appropriate targeting of therapies when gene therapy becomes available for humans with these conditions. The NHLBI Gene Therapy Resource Program (GTRP) could be leveraged during the application phase and post-award to accelerate research in studying the effects of gene therapy targeted to the respiratory muscles in animal models.

In summary, this NOSI encourages scientists in the space of muscular dystrophies to investigate respiratory function, and scientists in sleep-disordered breathing, ventilatory control and respiratory pathobiology and physiology to bring their expertise to research in the respiratory implications of these neuromuscular diseases. There is a possibility of cross-collaboration between disciplines that will bring synergy to research in diseases that are primarily neuromusculoskeletal with a profound and debilitating impact on the patient’s quality of life, largely due to pulmonary limitation. This is an opportunity to understand ways to effectively help patients remain in optimal pulmonary health for responding to currently available therapies, and potentially to future innovative therapies that are in the pipeline.

This notice applies to due dates on or after September 25, 2022 and subsequent receipt dates through January 7, 2025.

NOT-HL-22-025