{"doi":"10.1371/journal.pone.0304099","title":"Functional trajectories before and after loss of ambulation in Duchenne muscular dystrophy and implications for clinical trials","abstract":"This study examined functional trajectories of subjects during the transition phase between ambulatory and non-ambulatory Duchenne muscular dystrophy (DMD) to inform clinical trial designs for new therapeutics. Ambulatory, pulmonary, and upper limb function leading up to loss of ambulation (LoA) and non-ambulatory measures following LoA were quantified; time ordering of pulmonary and upper limb milestones relative to LoA were determined; and the 10-second time threshold for 10-meter walk/run (10MWR) as a marker of approaching LOA was explored. Included in this analysis were 51 subjects aged between 7 and 18 years who experienced LoA during follow-up in the PRO-DMD-01 natural history study. Mean age at LoA was 12.7 (7.1-18.6) years. Mean annual rates of decline in forced vital capacity (FVC) <80%-predicted and performance of upper limb (PUL) 1.2 total score were smaller before than after LoA, but not significantly (FVC %-predicted: 5.6% vs. 10.1%, p = 0.21; PUL 1.2 total score: 2.3 vs. 3.8 units, p = 0.20). More than half of patients experienced clinically significant deficits in FVC %-predicted and PUL 1.2 before experiencing LoA. Among subjects with baseline 10MWR >10 s, those with <1 year to LoA had similar mean ages but significantly worse mean ambulatory function at baseline compared to those with ≥1 year to LoA. Enriching DMD clinical trials for patients with declining pulmonary or upper limb function is achievable without restricting enrollment to non-ambulatory patients. The sequencing of LoA and initial deficits in pulmonary and upper limb function varied across patients and highlights the potential for composite outcomes or multi-outcome trial designs to assess disease-modifying therapies more comprehensively.","journal":"PLoS ONE","year":2024,"id":428192,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":13,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9457,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2024-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":260471,"name":"James Signorovitch","orcid":"0000-0002-4067-8962","position":1,"is_corresponding":false},{"id":297632,"name":"Eugenio Mercuri","orcid":"0000-0002-9851-5365","position":2,"is_corresponding":false},{"id":463481,"name":"E. Niks","orcid":"0000-0001-5892-5143","position":3,"is_corresponding":false},{"id":344371,"name":"Brenda Wong","orcid":"0000-0002-0971-9789","position":4,"is_corresponding":false},{"id":1229389,"name":"Mirko Fillbrunn","orcid":"0000-0002-8037-703X","position":5,"is_corresponding":false},{"id":478784,"name":"Gautam Sajeev","orcid":"0000-0002-1827-8938","position":6,"is_corresponding":false},{"id":1229857,"name":"Erica Yim","orcid":null,"position":7,"is_corresponding":false},{"id":1037603,"name":"Ibrahima Dieye","orcid":null,"position":8,"is_corresponding":false},{"id":479969,"name":"Debra Miller","orcid":null,"position":9,"is_corresponding":false},{"id":478786,"name":"Susan J. Ward","orcid":"0000-0002-5729-5263","position":10,"is_corresponding":false},{"id":344364,"name":"Nathalie Goemans","orcid":"0000-0002-5157-7155","position":11,"is_corresponding":false},{"id":1229858,"name":"Investigators from the PRO-DMD-01 Study, Collaborative Trajectory Analysis Project (cTAP)","orcid":null,"position":12,"is_corresponding":false},{"id":295921,"name":"Craig M. McDonald","orcid":"0000-0002-8779-3220","position":0,"is_corresponding":true}],"reference_count":42,"raw_metadata":null,"created_at":"2026-07-19T01:58:57.592578Z","pmid":"38829874","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}