S.P.21 Clinical outcome measures in Collagen 6 (COL6) and Laminin [alpha]2(LAMA2) related congenital muscular dystrophy

• Published in: Neuromuscular disorders : NMD Vol. 22; no. 9-10; p. 893
• Main Authors: Meilleur, K G, Jain, M, Kim, E, Hynan, L, Shieh, CY, Waite, M, Duong, T, Glanzman, A, Main, M, Rose, K, McGuire, M, Bendixen, R, Foley, R, Donkervoort, S, Schindler, A, Kokkinis, A, Hartnett, E J, Leach, M, Dastgir, J, North, K, Muntoni, F, Rutkowski, A, Bonnemann, C G
• Format: Journal Article
• Language: English
• Published: 01.10.2012
• Subjects: Indexing in process
• ISSN: 0960-8966
• DOI: 10.1016/j.nmd.2012.06.296

Potential therapies targeting primary deficiencies and downstream targets are under development for two extracellular matrix related congenital muscular dystrophy (CMD) subtypes, COL6 and LAMA2. However, outcome measures for clinical trials have not been validated in CMD. We performed a pilot study of various outcomes measures to test the feasibility of obtaining measurements in CMD and to validate their use for future clinical trials. Twenty-nine patients participated in the study (16 COL6 and 13 LAMA2). Measures tested included: myometry (knee flexion, elbow flexion and extension, cervical flexion in sitting) forced vital capacity sitting in liters (FVC), Motor Function Measure 32 (MFM32), North Star Ambulatory Assessment (NSAA), and Hammersmith Functional Motor Scales. We performed Spearman Rank analysis to assess their correlations. Our study revealed the following: myometry measures reflect feasibility of obtaining reproducible measurements, including knee flexion, elbow flexion and elbow extension, which correlated with MFM32 total score (r = 0.59-0.69, p < 0.003). FVC correlated significantly with all three domains of the MFM32 (range r = 0.48-0.70, p < 0.009) and MFM32 total score (r = 0.664, p < .001) and myometry measures (range r = 0.73-0.84, p < .001). The NSAA correlated with the MFM32 total score (r = 0.86, p < 0.001) and FVC (r = 0.63, p = 0.001), as did the Hammersmith (MFM32 r = 0.93, p < 0.001; FVC r = 0.57, p < 0.001). Preliminary results from this study of outcome measures in patients with COL6 and LAMA2 related CMDs indicate the above measures correlate highly and significantly with each other, demonstrating the feasibility of measurements and initial validation in CMD patients. Studies are underway to validate the MFM32 further in this patient group. In the next phase of the study, we will compare outcomes over 3 years and assess their sensitivity to change and ability to characterize disease progression in COL6 versus LAMA2 patients and in ambulatory versus non-ambulatory patients.