We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Natural history, outcome measures and trial readiness in LAMA2-related muscular dystrophy and SELENON-related myopathy in children and adults: protocol of the LAST STRONG study.
- Authors
Bouman, Karlijn; Groothuis, Jan T.; Doorduin, Jonne; van Alfen, Nens; Udink ten Cate, Floris E. A.; van den Heuvel, Frederik M. A.; Nijveldt, Robin; van Tilburg, Willem C. M.; Buckens, Stan C. F. M.; Dittrich, Anne T. M.; Draaisma, Jos M. T.; Janssen, Mirian C. H.; Kamsteeg, Erik-Jan; van Kleef, Esmee S. B.; Koene, Saskia; Smeitink, Jan A. M.; Küsters, Benno; van Tienen, Florence H. J.; Smeets, Hubert J. M.; van Engelen, Baziel G. M.
- Abstract
<bold>Background: </bold>SELENON (SEPN1)-related myopathy (SELENON-RM) is a rare congenital myopathy characterized by slowly progressive proximal muscle weakness, early onset spine rigidity and respiratory insufficiency. A muscular dystrophy caused by mutations in the LAMA2 gene (LAMA2-related muscular dystrophy, LAMA2-MD) has a similar clinical phenotype, with either a severe, early-onset due to complete Laminin subunit α2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit α2 deficiency. For both muscle diseases, no curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data and appropriate clinical and functional outcome measures are needed to reach trial readiness.<bold>Methods: </bold>LAST STRONG is a natural history study in Dutch-speaking patients of all ages diagnosed with SELENON-RM or LAMA2-MD, starting August 2020. Patients have four visits at our hospital over a period of 1.5 year. At all visits, they undergo standardized neurological examination, hand-held dynamometry (age ≥ 5 years), functional measurements, questionnaires (patient report and/or parent proxy; age ≥ 2 years), muscle ultrasound including diaphragm, pulmonary function tests (spirometry, maximal inspiratory and expiratory pressure, sniff nasal inspiratory pressure; age ≥ 5 years), and accelerometry for 8 days (age ≥ 2 years); at visit one and three, they undergo cardiac evaluation (electrocardiogram, echocardiography; age ≥ 2 years), spine X-ray (age ≥ 2 years), dual-energy X-ray absorptiometry (DEXA-)scan (age ≥ 2 years) and full body magnetic resonance imaging (MRI) (age ≥ 10 years). All examinations are adapted to the patient's age and functional abilities. Correlation between key parameters within and between subsequent visits will be assessed.<bold>Discussion: </bold>Our study will describe the natural history of patients diagnosed with SELENON-RM or LAMA2-MD, enabling us to select relevant clinical and functional outcome measures for reaching clinical trial-readiness. Moreover, our detailed description (deep phenotyping) of the clinical features will optimize clinical management and will establish a well-characterized baseline cohort for prospective follow-up.<bold>Conclusion: </bold>Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD.<bold>Trial Registration: </bold>This study has been approved by medical ethical reviewing committee Region Arnhem-Nijmegen (NL64269.091.17, 2017-3911) and is registered at ClinicalTrial.gov ( NCT04478981 ).
- Subjects
MUSCULAR dystrophy; NATURAL history; FACIOSCAPULOHUMERAL muscular dystrophy; MAGNETIC resonance imaging; DUAL-energy X-ray absorptiometry; MUSCLE weakness
- Publication
BMC Neurology, 2021, Vol 21, Issue 1, p1
- ISSN
1471-2377
- Publication type
journal article
- DOI
10.1186/s12883-021-02336-z