AETIONOMY, a Cross-Sectional Study Aimed at validating a new taxonomy of Neurodegenerative Diseases: Study design and subject characteristics

Background Although advances in the understanding of neurodegenerative diseases (NDDs) have led to improvements in classification and diagnosis and most importantly to new therapies, the unmet medical needs remain significant due to high treatment failure rates. The AETIONOMY project funded by the Innovative Medicine Initiative (IMI) aims at using multi-OMICs and bioinformatics to identify new classifications for NDDs based on common molecular pathophysiological mechanisms in view of improving the availability of personalised treatments. Objectives The purpose of the AETIONOMY cross-sectional study is to validate novel patient classification criteria provided by these tools. Methods This was a European multi centre, cross-sectional, clinical study conducted at 6 sites in 3 countries. Standardised clinical data, biosamples from peripheral blood, cerebrospinal fluid, skin biopsies, and data from a multi-OMICs approach were collected in patients suffering from Alzheimer’s and Parkinson’s disease, as well as healthy controls. Results From September 2015 to December 2017 a total of 421 participants were recruited including 95 Healthy Controls. Nearly 1,500 biological samples were collected. The study achieved its objective with respect to Parkinson’s disease (PD) recruitment, however it was unable to recruit many new Alzheimer Disease (AD) patients. Overall, data from 413 evaluable subjects (405 PD and 8 AD) are available for analysis. PD patients and controls were well matched with respect to age (mean 63.4 years), however, close gender matching was not achieved. Approximately half of all PD patients and one At-Risk subject were taking dopamine agonists; rates of Levodopa usage were slightly higher (∼60%). Median MDS-UPDRS Part III Scores (OFF state) ranged from 45 (SD 18) in those with Genetic PD to 2 (SD 3) in Healthy Controls. The standardised methodologies applied resulted in a high-quality database with very few missing data. Conclusion This is one of the collaborative multi-OMICs studies in individuals suffering from PD and AD involving a control group. It is expected that the integration of data will provide new biomarker-led descriptions of clusters of patient subgroups. ### Competing Interest Statement JC Corvol reports grants from IMI (grant agreement no. 115568) in relationship with this study; grants from Sanofi outside this work; scientific advisory board or speaker fees from Ever Pharma, Denali, Biogen, Air Liquide, BrainEver, Theranexus, and BMS outside this work. SB is an employee of UCB Pharma SA. SC has nothing to disclose. BC is an employee of UCB Pharma SA. JM is an employee of UCB Pharma SA. GM has nothing to disclose. OR reports grants from ANR, CHU de Toulouse, France-Parkinson, INSERM-DHOS, MJFox Foundation, PHRC, European Commission (FP7, H2020) outside of this work; consulting fees from AbbVie, Adamas, Acorda, Addex, AlzProtect, Apopharma, Astrazeneca, Bial, Biogen, Britannia, Buckwang, Clevexel, Denali, INC Reasearch, Lundbeck, Lupin, Merck, MundiPharma, Neuratris, Neuroderm, Novartis, ONO Pharma, Osmotica, Oxford Biomedica, Parexel, Pfizer, Prexton Therapeutics, Quintiles, Sanofi, Servier, Sunovion, Théranexus, Takeda, Teva, UCB, Vectura, Watermark Research, XenoPort, XO, Zambon, outside of this work. WGM reports fees for editorial activities with Springer, has served as advisor for Sanofi, Lundbeck, Biohaven and Affiris, and has received teaching honoraria from UCB and Boehringer Ingelheim outside of this work. EM has nothing to disclose. AFS, HC, IM, and PT have nothing to disclose. RSV reports scientific advisory board fees from Ionis Pharmaceuticals and Wave Life Sciences outside this work. MTH, JLM, and UW have nothing to disclose. PS reports honorarium from AbbVie, Safoni Genzyme and Shire outside of this work. PS is an employee of UCB Pharma SA. MHA has nothing to disclose. ### Clinical Trial This observational study was not registered because at the time of submission, 5 years ago, the design did not fit with ClinicalTrials.gov requirements (not suited for observational studies) ### Funding Statement The research leading to these results has received support from the Innovative Medicines Initiative Joint Undertaking under grant agreement no. 115568, resources of which are composed of financial contribution from the European Union's Seventh Framework Programme (FP7/2007-2013) and EFPIA companies' in-kind contribution. ### Author Declarations All relevant ethical guidelines have been followed and any necessary IRB and/or ethics committee approvals have been obtained. Yes All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes Any clinical trials involved have been registered with an ICMJE-approved registry such as ClinicalTrials.gov and the trial ID is included in the manuscript. Not Applicable I have followed all appropriate research reporting guidelines and uploaded the relevant Equator, ICMJE or other checklist(s) as supplementary files, if applicable. Yes All data are available on request to the corresponding author