Quantitative MRI, valuable surrogate biomarkers in monitoring disease progression of DMD, an analysis of Genethon’s multicentric natural history study

Topic:

Clinical Trials

Poster Number: 38 S

Author(s):

fei cao, MD, Genethon, 1bis rue de l'international, Evry France, Vincent Laugel, MD, Hospital Hautepierre, Strasbourg, France, Silvana De Lucia, MD, Institut I-Motion, Hôpital Trousseau, 26 avenue du Dr Arnold Netter, Paris, France, Jean Davion, MD, Pediatric neurology, Hospital of Lille, France, Laure Le-Goff, MD, Hôpital Femme Mère Enfant, 59 Boulevard Pinel, 69500 Bron, France, Michela Guglieri, MD, Newcastle University, Newcastle upon Tyne, England, UK , Caroline Espil, MD, Service de Neuropédiatrie, Hôpital des enfants Pellegrin, Place Amélie Raba Léon, Bordeaux, France, Brigitte Chabrol, MD, Hôpital d’Enfants, CHU Timone, 264 rue saint pierre, 13385 Marseille cedex 05 , France, Andreea Seferian, MD, Institut I-Motion, Hôpital Trousseau, 26 avenue du Dr Arnold Netter, Paris, France, Tristan Montier, MD, CHU Morvan, Service de Génétique Médicale et Biologie de la Reproduction, 2 avenue Foch, Brest, Fr, Benjamin Marty, PhD, Institut of Myology, NMR Laboratory – Spectroscopy Laboratory, 47-53 BD de l'Hôpital, Paris, Fr, Harmen Reyngoudt, PhD, Institut of Myology, NMR Laboratory – Spectroscopy Laboratory, 47-53 BD de l'Hôpital, Paris, Fr, Laurent Thibaut, Genethon, 1bis rue de l'international, Evry France, Rachida-Lydie Zanfongnon, Genethon, 1bis rue de l'international, Evry France, Eric Guemas, Msc, BIOSSEC, 9 rue Anatole de la Forge, 75017 Paris, France, Gerald Perret, PhD, Généthon, Arnaud Valent, MD, Genethon, 1bis rue de l'international, Evry France, francesco Muntoni, MD, Hospital for Children Foundation Trust, London, UK

Duchenne muscular dystrophy (DMD) is a severe disease caused by dystrophin gene mutations, leading to progressive muscle degeneration and early death. Pathological changes include muscle necrosis, inflammation and fibrofatty replacement. Clinical course is highly heterogeneous, and functional assessments may be influenced by motivation, fatigue, or cognitive factors.
Quantitative Magnetic resonance imaging (qMRI) provides a noninvasive, objective means to monitor muscle volume (contractile cross-sectional area: cCSA) and fat fraction (FF), both strong predictors of disease progression. We analyzed FF, cCSA, and their correlations with clinical outcomes – NSAA, stride velocity 95th centile (SV95C) and serum CK – in 73 corticosteroid-treated DMD boys aged 5–9 years, enrolled in a multicenter natural history study with standardized 6-month assessments (NCT03882827). MRIs were centrally read.
Both cCSA and FF showed excellent symmetric patterns. For glutei, hamstrings, and quadriceps, baseline mean cCSA (cm²) were 14.29, 7.73 and 14.80, respectively. Annual % changes from baseline were 0.62, 4.19, -4.92 in the [5–8y[ and -8.66, -9.37 and -9.22 in the [8–10y] age group. Baseline mean FF (%) were 23.5, 15.2, and 14.2, with annual increases of +7.3, +4.7 and +6.0 in boys <8 years, and +9.5, +9.5, and +10.0 in those ≥8 years. Regression analysis revealed a slight increase in cCSA before age 8, followed by a progressive decline, while FF increased progressively with age which became more pronounced from approximately 8 years onward. FF showed moderate to good correlations with clinical outcomes (|r| = 0.52 for NSAA, 0.62 for SV95C and 0.63 for serum CK. cCSA correlations were slightly lower: |r| = 0.56, 0.58 and 0.48 respectively. These findings support qMRI—particularly FF—as an objective, reliable, age-consistent biomarker in DMD. Its ability to capture muscle-specific changes beyond functional tests and serum CK underscores its further relevance as a surrogate endpoint in clinical trials.