Biomarker for Duchenne Muscular Dystrophy

Study Overview
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Brief Summary
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International, multicenter, observational, longitudinal study to identify biomarker/s for Duchenne Muscular Dystropy (DMD) and to explore the clinical robustness, specificity, and long-term variability of these biomarker/s.

Detailed Description
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Duchenne Muscular Dystrophy (DMD) is a devastating inherited neuromuscular disorder that affects 1 in 3300 live male births (females can be mildly affected carriers). DMD causes progressive weakness and loss of muscle mass, with symptoms usually appearing in early childhood. DMD arises from mutations in the DMD gene that codes for dystrophin. The DMD gene is located on the short arm of chromosome X (locus Xp21) and codes for dystrophin, containing 3685 amino acid residues. 60-65% of DMD mutations are large dele-tions, 10-30% are nonsense and frame-shift mutations, 5-15% are duplications, and 2% are intronic or 5'- and 3'-UTR alterations.Dystrophin aggregates as a homotetramer in the skeletal muscles or associates with actin and Dystrophin-Associated Glycoproteins (DAGs), forming a stable complex that interacts with laminin in the extracellular matrix. Dystrophin is considered a key structural element in the muscle fiber, whose primary function is to stabilize plasma mem-brane, while the DAGs maintain the sarcolemmal stability by mediating the complex interactions of the muscle membrane and extracellular environment. The low levels of dystrophin lead to cellular instability and progressive leakage of intracellular components, explaining the characteristically high levels of creatine phosphokinase (CPK) in the blood of DMD patients. Biomarkers serve as measurable indicators of normal biological or pathological processes. They are typically directly linked to genetic variants in specific genes and can predict, diagnose, monitor, and assess the severity of a disease. It is the goal of this study to identify, validate, and monitor biochemical markers from DMD affected participants.

Official Title
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Biomarker for Duchenne Muscular Dystrophy: An International, Multicenter, Observational, Longitudinal Protocol

Conditions
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Increased Lordosis/Scoliosis, Hyporeflexia, Duchenne Muscular Dystrophy, Red-Green Color Blindness, Lordosis, Scoliosis, Muscular Atrophy, Muscular Weakness

Participation Criteria
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Eligibility Criteria
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INCLUSION CRITERIA Informed consent is obtained from the parent/ legal guardian The participant is aged between 2 months and 50 years The diagnosis of DMD is genetically confirmed by CENTOGENE EXCLUSION CRITERIA Informed consent is not obtained from the parent/ legal guardian. The participant is younger than 2 months or older than 50 years The diagnosis of DMD is not genetically confirmed by CENTOGENE

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 50 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Participants with Duchenne Muscular Dystrophy (DMD)<br>Participants diagnosed with Duchenne Muscular Dystrophy (DMD) aged between 2 months and 50 years | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Identification of DMD biomarker/s | All samples will be analyzed for the identification of biomarker/s via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC. | 36 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exploring the clinical robustness, specificity, and long-term variability of DMD biomarker/s | Samples will be analyzed for the identified biomarker candidates via Liquid Chromatography Multiple Reaction-monitoring Mass Spectrometry (LC/MRM-MS) and compared to merged control, in order to establish the disease-specific biomarker/s. The LC/MRM-MS is performed on an ABSciex 6500 triple quadrupole mass spectrometer, coupled with a Waters Acquity UPLC. | 36 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Duchenne Disease, Biomarker