Sampling and biomarker OPtimisation and Harmonisation In ALS and other motor neuron diseases (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.

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 motor system (upper motor neurons in the motor cortex and lower motor neurons in the spinal cord) is preferentially affected. Whilst correlation between clinical and autopsy diagnosis is close to 100%, validated neurochemical biomarkers for monitoring disease activity, earlier diagnosis and defining prognosis are lacking. Thus, 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 act as an important communication channel between this consortium and the broader international ALS/Neurodegeneration field, to ensure that the optimization efforts are consistently applied. Ultimately, the platform will establish a permanent Interactive European ALS biomarker tool for all researchers, and will enable ongoing optimization/harmonization of novel biomarkers using an integrated and robust pan-European ALS methodology. The platform will allow interaction with those of other cognate groups (e.g the NEALS group within the US), with patient groups and other relevant stakeholders.

ALS is one of the most devastating neurodegenerative diseases for which no therapy exist. As such, the existence of a set of optimized and standardized methods for collection, preservation and analysis of different biomarkers necessary to evaluate diagnosis and disease progression of ALS and other motor neuron diseases will be an enormous advance in the investigation of this condition at several levels, possibly transferable to other forms of neurodegeneration.

The impact would involve many different areas:

1- Systematic multicentre investigation to permit an earlier and more reliable diagnosis has two major implications:
a. Less time consuming expensive investigations before reaching the final diagnosis of ALS, avoiding unnecessary interventions such as surgical procedures
b. Earlier clinical trial entry with high chances of defining an effective drug
2- All methods, database, biomarker essays, and biomarker in SOPHIA will be shared with other members of the scientific community devoted to ALS and to other ND.
3- The concept of this project (pan-European SOPs) can be expanded to other ND resulting in a driving force for shared biomarker research.
4- Better understanding of ALS etiopathogenesis and natural history.
5- The project will increase the interest of the international scientific community in relation to ALS.
6- Identification of consistent biomarker in ALS will permit less expensive, smaller, and shorter trials with better stratified early ALS patients, with increased probability to find an effective drug.
7- Availability of more precise measures of disease activity and disease progression will improve trial design and thereby attract pharmaceutical industry to investigate new compounds in ALS.
8- Improved patient care as a systematic questionnaire is applied to permit a proper evaluation. A potential biomarker will allow a more scientific evaluation of all interventions.
9- Patients association satisfied with higher care quality: all interventions will be more appropriately measured due to this project.
10- The finding of potential biomarker(s) will allow the development of new European commercial opportunities to develop biomarker detection kits for use in neurodegeneration clinical practice.
11- The project will demonstrate the impact of a large European multicentric project in relation to a relatively rare disorder acting as a template for other conditions in the future.
12- SOPHIA will for the first time establish an Interactive European ALS biomarker website, that serves as a vehicle to support implementation of the pan-European methodology on ALS biomarker optimization and harmonization. This platform engages with end-users in an early stage, thereby improving acceptation and implementation of project results by these stakeholders. Possibilities for co-funding and member fees will be examined to ensure that this platform will be sustainable. When successful, this platform can be extended to / implemented in other ND areas.