RT Journal Article
SR Electronic
T1 X-linked myotubular myopathy
JF Neurology
JO Neurology
FD Lippincott Williams & Wilkins
SP e1852
OP e1867
DO 10.1212/WNL.0000000000007319
VO 92
IS 16
A1 Annoussamy, Mélanie
A1 Lilien, Charlotte
A1 Gidaro, Teresa
A1 Gargaun, Elena
A1 Chê, Virginie
A1 Schara, Ulrike
A1 Gangfuß, Andrea
A1 D'Amico, Adele
A1 Dowling, James J.
A1 Darras, Basil T.
A1 Daron, Aurore
A1 Hernandez, Arturo
A1 de Lattre, Capucine
A1 Arnal, Jean-Michel
A1 Mayer, Michèle
A1 Cuisset, Jean-Marie
A1 Vuillerot, Carole
A1 Fontaine, Stéphanie
A1 Bellance, Rémi
A1 Biancalana, Valérie
A1 Buj-Bello, Ana
A1 Hogrel, Jean-Yves
A1 Landy, Hal
A1 Servais, Laurent
YR 2019
UL http://n.neurology.org/content/92/16/e1852.abstract
AB Objectives Because X-linked myotubular myopathy (XLMTM) is a rare neuromuscular disease caused by mutations in the MTM1 gene with a large phenotypic heterogeneity, to ensure clinical trial readiness, it was mandatory to better quantify disease burden and determine best outcome measures.Methods We designed an international prospective and longitudinal natural history study in patients with XLMTM and assessed muscle strength and motor and respiratory functions over the first year of follow-up. The humoral immunity against adeno-associated virus serotype 8 was also monitored.Results Forty-five male patients aged 3.5 months to 56.8 years were enrolled between May 2014 and May 2017. Thirteen patients had a mild phenotype (no ventilation support), 7 had an intermediate phenotype (ventilation support less than 12 hours a day), and 25 had a severe phenotype (ventilation support 12 or more hours a day). Most strength and motor function assessments could be performed even in very weak patients. Motor Function Measure 32 total score, grip and pinch strengths, and forced vital capacity, forced expiratory volume in the first second of exhalation, and peak cough flow measures discriminated the 3 groups of patients. Disease history revealed motor milestone loss in several patients. Longitudinal data on 37 patients showed that the Motor Function Measure 32 total score significantly decreased by 2%. Of the 38 patients evaluated, anti–adeno-associated virus type 8 neutralizing activity was detected in 26% with 2 patients having an inhibitory titer >1:10.Conclusions Our data confirm that XLMTM is slowly progressive for male survivors regardless of their phenotype and provide outcome validation and natural history data that can support clinical development in this population.ClinicalTrials.gov identifier NCT02057705.AAV=adeno-associated virus; CHOP-INTEND=Children's Hospital of Philadelphia Infant Test of Neuromuscular Disorders; FEV1=forced expiratory volume in the first second of exhalation; FVC=forced vital capacity; MEP=maximum expiratory pressure; MFM=Motor Function Measure; MHFMS=Modified Hammersmith Functional Motor Scale; MIP=maximum inspiratory pressure; NSAA=North Star Ambulatory Assessment; PCF=peak cough flow; XLMTM=X-linked myotubular myopathy