Abstract
Background: 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 a2 deficiency (merosin-deficient congenital muscular dystrophy type 1A (MDC1A)), or a mild, childhood- or adult-onset due to partial Laminin subunit a2 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.Methods: 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.Discussion: 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.Conclusion: Our natural history study is an essential step for reaching trial readiness in SELENON-RM and LAMA2-MD.
Original language | English |
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Article number | 313 |
Number of pages | 14 |
Journal | BMC Neurology |
Volume | 21 |
Issue number | 1 |
DOIs | |
Publication status | Published - 12 Aug 2021 |
Keywords
- LAMA2
- Laminin subunit a2 deficiency
- Merosin-deficient congenital muscular dystrophy type 1A (MDC1A)
- SELENON
- SEPN1
- Natural history
- Outcome measures
- Trial readiness
- All ages
- SKELETAL-MUSCLE PATHOLOGY
- SELENOPROTEIN-N
- OXIDATIVE STRESS
- REFERENCE VALUES
- DUCHENNE DYSTROPHY
- CLINICAL-TRIALS
- RELIABILITY
- VALIDATION
- ULTRASOUND
- QUESTIONNAIRE