Biomarkers of Lewy body Parkinson's disease (PD) may be readily informed in SNCA multiplication families. Chronic alpha-synuclein over expression is a relatively homogenous and well defined cause of parkinsonism and dementia. Neurodegeneration resulting from SNCA multiplication segregates in an age-associated but dominant fashion. Moreover, SNCA gene dosage is directly correlated with gene/protein expression, age of onset and disease progression; SNCA triplication carriers have a mean onset of 38.5 years (95% CI 28-45, n=15) years, and generally have a much faster progression to dementia and death than duplication carriers (mean 50.2 years, 95% CI 46-50, n=41)(as reviewed by 9). However, carriers may manifest symptoms <30 years or remain clinically asymptomatic throughout their life. Although environment and lifestyle are important, we hypothesize clinical variability within and between SNCA multiplication pedigrees is a function of genetic variability.
In this project we propose to assess clinical genetic biomarker correlation in SNCA multiplication families using harmonized methods and assessments. Communication between Consortium Investigators and SNCA multiplication families will inform, coordinate and enable imminent clinical trials. Several companies have therapeutic efforts directed at alpha-synuclein as the target to prevent or clear Lewy pathology. In idiopathic PD many advances have been made in clinical trial design. Nevertheless, a major challenge is which subjects are best suited, over what period given disease heterogeneity, and how efficacy should be assessed given the lack of informative biomarkers. The SNCA Multiplication Consortium is to provide a well-characterized, longitudinally followed, pedigree-based resource for informative pilot studies.
We have collected samples from 58 SNCA multiplication families across 22 separate institutions and are strongly interested to include and identify more probands. We can provide SNCA copy number screening for those that have samples they would like checked for SNCA multiplications. For further information and to find out how you can be involved, please contact Tara Candido, firstname.lastname@example.org .