Limb Girdle Muscular Dystrophy Clinical Trial
Official title:
MRI-phenotyping of Patients With Pathogenic Anoctamin 5 Variants
A large cohort of MRI scans from patients with pathogenic variants in the anoctamin 5 gene will be collected through an international collaboration to better describe muscle involvement.
Background: The anoctamin 5 gene (ANO5) encodes the anoctamine 5 protein that act as a calcium-sensitive chloride channel. The protein is preferentially expressed in skeletal and cardiac muscle and bone and likely acts in the repair of the cell membrane. Pathogenic ANO5 variants inherited in a autosomal recessive trait give rise to three main phenotypes: Limb-girdle muscular dystrophy type R12 (LGMDR12, formerly classified as LGMD2L), Miyoshi distal muscular dystrophy type 3 (MMD3), and asymptomatic hyperCKemia). As the name implies, patients with LGMDR12 are affected more proximally and patients with MMD3 more distally, but the definition and distinction between the two entities is unclear. Men with anoctaminopathy are more severely affected than women. Cardiac disease such as arrhythmias and cardiomyopathy as well as bulbar symptoms or respiratory failure are very rare in anoctaminopathies. Onset is in adulthood and disease progression is slow, generally with a later onset and disease progression than seen in other LGMDs. Ambulation is preserved until late in the disease course. However, only few studies based on small case series have investigated the phenotype of patients with ANO5 mutations using MRI. There is therefore a need to investigate a larger international group of patients using MRI to properly describe which muscles are affected in men and women with anoctaminopathy. The spectrum of phenotypes in anoctaminopathies resembles that seen in dysferlinopathies, and in the latter group, it has been shown that the former division into LGMDR2 (formally LGMD2B) and Miyoshi distal muscular dystrophy type 2 (MMD2) is rather arbitrary. Our hypothesis is that this may very well also be the case for LGMDR12 and MMD3. A large MRI study would be able to shed light on this question. Muscle involvement in patients with ANO5 mutations is said to be asymmetric based on clinical assessments (7,8,10). The proposed study will also elucidate this by studying symmetry of muscle affection. Finally, the diseases severity is said to be marked between the two sexes, but this has not been quantified in any detail before. The proposed study will also be able to shed light on this. Aim: The aims of the project are: - To describe the muscle MRI phenotype in around 200 patients from multiple countries around the world. - To investigate if it makes sense to group patients with pathogenic ANO5 variants into proximal and distal myopathies. - To investigate to what extent the disease is asymmetric. - To investigate the difference in disease severity between sexes. - To investigate whether a phenotype-genotype correlation exists. Methods: Sites from all over the world will share an eCRF and their MRI data with Copenhagen Neuromuscular Center through the platform MyoShare. ;
Status | Clinical Trial | Phase | |
---|---|---|---|
Recruiting |
NCT04001595 -
Global FKRP Registry
|
||
Recruiting |
NCT05409079 -
Schulze Muscular Dystrophy Ability Clinical Study
|
N/A | |
Active, not recruiting |
NCT05906251 -
A Gene Transfer Study to Evaluate the Safety, Tolerability and Efficacy of SRP-6004 in Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2B/R2 (LGMD2B/R2, Dysferlin [DYSF] Related)
|
Phase 1 | |
Recruiting |
NCT05230459 -
A Study to Evaluate the Safety of AB-1003 (Previously LION-101) in Subjects With Genetic Confirmation of LGMD2I/R9 (Part1)
|
Phase 1/Phase 2 | |
Recruiting |
NCT03981289 -
Defining Clinical Endpoints in Limb Girdle Muscular Dystrophy (LGMD)
|
||
Completed |
NCT02836418 -
Study to Evaluate the Long-Term Safety, Tolerability, and Biological Activity of ATYR1940 in Participants With Limb Girdle and Facioscapulohumeral Muscular Dystrophy (FSHD)
|
Phase 1/Phase 2 | |
Active, not recruiting |
NCT03930628 -
Limb-Girdle Muscular Dystrophy Type 2I in Norway
|
||
Recruiting |
NCT05618080 -
Trial Readiness and Endpoint Assessment in LGMD R1
|
||
Completed |
NCT01066455 -
Cardiac Outcome Measures in Children With Muscular Dystrophy
|
N/A | |
Active, not recruiting |
NCT05206617 -
3 Year Follow up on ANO5 Patients
|
||
Completed |
NCT01126697 -
Clinical Trial of Coenzyme Q10 and Lisinopril in Muscular Dystrophies
|
Phase 2/Phase 3 | |
Withdrawn |
NCT02245711 -
Cell Therapy in Limb Girdle Muscular Dystrophy
|
Phase 1 | |
Withdrawn |
NCT02050776 -
Stem Cell Therapy in Limb Girdle Muscular Dystrophy
|
Phase 1 | |
Active, not recruiting |
NCT05876780 -
A Gene Transfer Single Dose Study to Evaluate the Safety, Tolerability and Efficacy of SRP-9003 in Non-Ambulatory and Ambulatory Participants With Limb Girdle Muscular Dystrophy, Type 2E/R4 (Beta-Sarcoglycan [β-SG] Deficiency)
|
Phase 1 | |
Recruiting |
NCT06378203 -
Rehabilitation in Muscular Dystrophies From the Hospital Facility to the Home: Pilot Project [RIMUDI]
|
N/A | |
Completed |
NCT04202627 -
Biomarker Development in LGMD2i
|
||
Not yet recruiting |
NCT06390566 -
Evolution of the Functional and Muscular State of Patients With Muscular Dystrophy 2A Belts
|
||
Completed |
NCT01081080 -
Cardiac Magnetic Resonance in Children With Muscular Dystrophy
|
N/A |