Progetti di ricerca

Which biomarker(s) are best suited to overcome current MRI interpretive issues and poor specificity in monitoring the effective response to therapy and the prediction of ARIA events? Irrespective of current legit debates on the clinical efficacy of amyloid-lowering therapeutics, several monoclonal antibodies… Leggi tutto (mAbs) are currently in clinical trials pipeline , including anti-TREM2 antagoist mAbs, or have entered accelerated FDA approval pathway. This means that 3 to 4 mAbs could potentially enter clinical practice in 2023. However, all of these high plaque-removing mAbs reported a common dose- and time-dependent incidence of ARIAs in up to 55% of the treated patients. In this framework, in order to minimize the risk of ARIAs, current trials limit enrollment to an extremely well-selected and radiographically monitored subpopulation of AD patients. Common criteria are the exclusion of patients with =5 cerebral microbleeds or cortical superficial siderosis at baseline and a control MRI before each biweekly/monthly infusion. This issue is challanging the generalizability of trials results, in particular concerning potential increased safety issues in real-word clinical settings. With 139 million of AD esteemed by 2050, and 60% of them living in low- and middle-income countries (2021 WHO report), longitudinal MRI monitoring plans for ARIA will hugely affect healthcare systems. This will potentially increase disparities, limiting accessibility to these therapeutics only to reach people and countries. In this framework, less costly and more accessible biomarkers will be of paramount importance for the future of AD immunotherapy. The UNIMIB-ARIA Toolkit Project aims at: 1) increase knowledge on the emerging evidence for neuroinflammation in the pathophysiology of ARIAs. 2) validate fluid-based biomarkers for improving diagnosis, prognosis, response to treatment, and prediction of ARIA-E recurrence compared to current state-of-the-art MRI images markers Thanks to the capillary activity and promotion we did in the last 10 years, including educational activities, at UNIMIB we are the National HUB for CAA and CAA-ri, receiving patients from almost all the main National centers (Spokes), the latter working as sub-spokes at regional and sub-regional level, in order to catch any patient also from very remote and rural areas. For these reasons, the National (Italy) biorepository should be considered an extremely excellent representation of the real-world clinical setting of the whole country. A gender-balanced Team (50% Female, 50% Male) of self-motivated and enthusiastic early career and young researcher composes the Teamwork. Addressing the aims of the UNIMIB-ARIA Project will be of paramount importance to increase generalizability and limit unnecessary restrictions to the future access of AD Therapeutics by the broaden community of AD and CAA patients, as well as to guide secondgeneration of more effective and safe therapeutics.