Functionalized Point of Care and 3D Printed Dental Aligners as Devices for Early Detection of Neurodegenerative Diseases

Registry record from ClinicalTrials.gov (NCT07870070). This is a study registration, not published results. Lead sponsor: Fondazione IRCCS Ca' Granda, Ospedale Maggiore Policlinico. Recruitment status: ACTIVE_NOT_RECRUITING. Study type: OBSERVATIONAL. Enrollment: 256 participants (ESTIMATED). Conditions: Neurodegenerative Diseases, Alzheimer's Disease. Primary outcome measures: miRNAs identification , till 31 January, 2027. Brief summary: The treatment of dementias of neurodegenerative origin is currently limited to symptomatic drugs that are unable to interfere with the underlying mechanisms of neurodegeneration, as the pathological processes leading to dementia begin decades before the onset of clinical symptoms. In this context, biomarkers for the diagnosis of Alzheimer's disease (AD), the most common form of dementia, are currently available but are either invasive, requiring lumbar puncture, or very expensive, such as PET imaging with amyloid and, potentially, tau tracers. Their widespread application across different clinical settings is therefore impractical. Accordingly, one of the major challenges in this field is the identification of peripheral screening biomarkers with a high negative predictive value (NPV), capable of identifying individuals who are negative for disease-associated biomarkers and can therefore be classified as healthy. Among the most promising biomarkers for neurodegenerative diseases are microRNAs (miRNAs), small non-coding RNA molecules. This study is part of the Italian National Recovery and Resilience Plan (PNRR) project on high-impact Non-Communicable Chronic Diseases (MCnT2), Project Code PNRR-POC-2023-12377354, funded by the Italian Ministry of Health/European Union - Next Generation EU - PNRR M6C2, Investment 2.1, "Enhancement and Strengthening of Biomedical Research within the Italian National Health Service." The participating institutions are Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico di Milano and Azienda Ospedaliero-Universitaria "Policlinico San Marco" di Catania. The main working hypotheses of the funded PNRR project are the identification of miRNAs that are dysregulated in patients with AD compared with age-matched healthy individuals and patients with non-AD conditions, and the development of a solution-based sensor for the simplified detection of the identified miRNAs. The sensor will exploit the biochemical methodology developed in Italian Patent No. IT102022000014740 (filed on July 13, 2022), which is capable of measuring the levels of specific enzymes in saliva. The project is structured into three Work Packages (WPs): WP1: Identification and validation of candidate miRNAs and calculation of their negative predictive value (NPV). WP2: Development and optimization of the solution-based sensor and assessment of its ability to detect the findings identified in WP1 using a simpler methodology. WP3: Testing of the sensor in a cohort of patients with AD and controls across different clinical settings, including neurological and dental clinics, in order to assess its applicability in real-world clinical practice. In this study, we aim to: identify the most significantly dysregulated miRNAs in the saliva of patients with AD (WP1); and develop and optimize a solution-based gold nanoparticle biosensor capable of detecting candidate miRNAs in saliva samples from both patients with AD and healthy individuals (WP2).