Towards a European Registry and Biorepository for Patients with Spinal and Bulbar Muscular Atrophy

Pathomechanisms of spinal and bulbar muscular atrophy (SBMA) have been extensively investigated and are partially understood, but no effective treatment is currently available for this disabling disorder. Its rarity, the slow disease progression, and lack of sensitive-to-change outcome measures render design and conduction of clinical trials a challenging task. Therefore, it is fundamental to strengthen the network of clinical centers interested in SBMA for clinical trial readiness. We propose to create and maintain an International SBMA Registry where as many well-characterized patients as possible can be included, with the following aims: facilitate planning of clinical trials and recruitment of patients, define natural history of the disease, characterize epidemiology, develop standards of care, and inform the community of patients about research progresses and ongoing trials. We also aim at developing harmonized and coordinated biorepositories. The experience obtained during the last years in the field of other neuromuscular disorders and of Huntington disease offers valuable precedents

210th ENMC International Workshop: Research and clinical management of patients with spinal and bulbar muscular atrophy, 27-29 March, 2015, Naarden, The Netherlands

Full report of the 210 ENMC meeting dedicated to SBMA. \u2022 Toward a European Consortium for SBMA. \u2022 Discussion on pathogenesis, protein quality control, and animal models. \u2022 Discussion of clinical outcomes and European registry for SBMA

Relations between C9orf72 expansion size in blood, age at onset, age at collection and transmission across generations in patients and presymptomatic carriers

A (GGGGCC)n repeat expansion in C9orf72 gene is the major cause of frontotemporal dementia (FTD) and amyotrophic lateral sclerosis (ALS). The relations between the repeats size and the age at disease onset (AO) or the clinical phenotype (FTD vs. ALS) were investigated in 125 FTD, ALS, and presymptomatic carriers. Positive correlations were found between repeats number and the AO (p < 10e 124) but our results suggested that the association was mainly driven by age at collection (p < 10e 124). A weaker association was observed with clinical presentation (p = 0.02), which became nonsignificant after adjustment for the age at collection in each group. Importantly, repeats number variably expanded or contracted over time in carriers with multiple blood samples, as well as through generations in parent-offspring pairs, conversely to what occurs in several expansion diseases with anticipation at the molecular level. Finally, this study establishes that measure of repeats number in lymphocytes is not a reliable biomarker predictive of the AO or disease outcome in C9orf72 long expansion carriers