Sampling, biomarker OPtimization and Harmonization In ALS (SOPHIA)

Amyotrophic Lateral Sclerosis (ALS) is one of the most devastating diseases in neurology affecting some 50,000 individuals at any time in Europe, and causing around 10,000 deaths each year. The main clinical features are weakness and wasting of muscles, but dementia may also occur. ALS represents a good model for study of all neurodegenerative conditions, as it has a characteristic phenotype, rapid progression and the correlation between diagnosis during life and autopsy diagnosis is close to 100%. However, validated neurochemical biomarkers for monitoring disease activity, for generating earlier diagnoses and for defining prognosis are lacking. Active European collaborations are in place for harmonizing clinical datasets, neuroimaging and neuropathology protocols. A preliminary strategy for harmonization of biological and tissue samples has been established. Standardized protocols for clinical data and sample collection are now urgently required for optimization and harmonization of biomarker development.
The overall aim of this proposal is to provide a common European strategy for the prioritization and selection of candidate biomarker domains for optimization and harmonization. This will in turn provide a long-term platform by which existing collaborative structures that are relevant to neurodegenerative disease biomarkers (including academic initiatives, co-funding strategies, biobanks, industrial efforts, private-public alliances) are integrated within an inclusive web-based virtual biobank. Samples and clinical/imaging/neurophysiologic and neuropathological datasets provided by participating members can then be optimally utilized to enable state of the art collaborative analyses.
The established platform will also act as an important communication channel between this consortium and the rest of the ALS/Neurodegeneration field to ensure that the optimization efforts are in line with the whole ALS/ND field, to avoid duplication of work, and to ensure better acceptance and utilization of the project results by all stakeholders. Ultimately, the platform will be used to disseminate the results to the whole ALS/Neurodegeneration field, and will act as a permanent Interactive European ALS biomarker platform for researchers to optimize/harmonize novel biomarkers using an established pan-European ALS methodology. The platform will also allow interaction with those of other cognate groups (e.g the NEALS group within the US) and with patient groups and other relevant stakeholders.

Tasks in the MRI component of SOPHIA:
T1. Registration of participating EU ALS centres to the Jena MRI database.
T2. Establish bidirectional interface to the core clinical data management.
T3. Assessment of acquisition parameters driving variability in T1W and DTI datasets
T4. Comparison of group-level results from different analysis platforms (SPM versus FSL versus TIFT).
T5. Identification of a standardised protocol for T1W and DTI acquisition.
T6. Linkage of core dataset and non-MRI biomarkers to individual MRI datasets to explore the additional value of a multimodal profile.
T7. Implementation of standardised protocol prospectively in ALS and healthy control subjects.
T8. Publication and international challenge of neurodegenerative disease research groups to test protocol against non-ALS neurodegenerative disease cases.
T9. Re-assessment of variability of both pre-processed MRIs and results post-analysis in prospective data, through multi-site data sharing (inter and intra-site variability).
T10. Correlation with post-mortem neuropathology reports in a subset of centers adhering to the standards of established European brain banks.
T11. Application of quality control systems to other MRI modalities i.e. resting state fMRI, MR spectroscopy and advanced fibre track analysis tools of DTI.
T12. Implementation of a continuous quality control framework which feeds back to participating centres.

This project has benefit for patients with MND and their carers, through the development of much-needed biomarkers of disease progression and phenotype. These can improve care planning and the development of therapeutic agents for a devastating neurological disorder.

The project will deliver standardization and harmonization of candidate biomarkers across multiple EU MND centres so that there is a coherent approach to this vital area of need, avoiding duplication of work and wasted resources. The inherent QC aspect means that valuable biofluid samples and MRI scans are acquired and stored consistently to allow meaningful comparison of results across centres.

The project establishes a platform that will be accessible to global research communities involved in neurodegenerative biomarker development, many of whom use similar biofluid and advanced MRI technology within other diseases. Information about variability of measures across sites, and issues of QC have great potential to save time and resources.