The International Clinical Outcome Study in Dysferlinopathy recruited 328 participants between 2012 and 2022. Almost all participants were symptomatic at enrolment.
Pre-symptomatic or very early disease stage diagnoses are increasingly generated through incidental CK results, screening for segregation analysis, or the diagnosis of a symptomatic family member leads to sibling diagnoses. An established pre- or early symptomatic diagnosis provides the opportunity to expand current knowledge of the early natural history and disease onset.
COS PrePARED has been set up for this purpose and aims to:
1) define the early natural history of dysferlin-deficient limb girdle muscular dystrophy (dysferlinopathy/LGMDR2) by monitoring muscle function, strength, and biomarkers of muscle pathology.
2) identify early indicators of disease onset that will inform recognition, diagnosis, care considerations, clinical trial design and treatment indications.
Participants can be included if they have a confirmed genetic diagnosis of dysferlin-deficient LGMDR2 (two pathogenic mutations DYSF ), can stand on tiptoes on both feet at the same time and can hop clearing foot off floor.
5 participants (aged 13-19, 3 male, 2 female) have been recruited at abstract submission. Baseline visit data will be presented
Participants are assessed using quantitative MRI (T2, Dixon), instrumented gait assessment and functional outcome measures (NSAD, 100MWR, Bruiniks-Oseretsky test of motor function, and selected functional items from the 1000 norms project to include Star Jump, Long Jump, Balance Beam, push ups, sit ups) over a five year period. Patient reported outcome measures (ACTIVLIM, McGill Pain, PROMIS Fatigue and Fatigue Severity score, IPAQ, RAPA) and age-appropriate quality of life measures will be completed.
Due to the rarity of pre-symptomatic diagnoses, we seek the support of MDA centres to identify eligible participants. The recruitment target is 20. All participants will be seen in Newcastle,. UK. International travel costs will be reimbursed.
The study of early symptomatic patients will inform gene replacement therapy approaches which are likely to be most effective in early stages of disease progression. The COS PrePARED model could be applied to other neuromuscular diseases.
COS PRePARED is funded by the Jain Foundation.
We are grateful to the young people and families who have committed to participate in this study over the next 5 years.