Lessons learned from the failure of solanezumab as a prospective treatment strategy for Alzheimer's disease.

INTRODUCTION: In the last decade, the efforts conducted for discovering Alzheimer's Disease (AD) treatments targeting the best-known pathogenic factors [amyloid-ß (Aß), tau protein, and neuroinflammation] were mostly unsuccessful. Given that a systemic failure of Aß clearance was supposed to primarily contribute to AD development and progression, disease-modifying therapies with anti-Aß monoclonal antibodies (e.g. solanezumab, bapineuzumab, gantenerumab, aducanumab, lecanemab and donanemab) are ongoing in randomized clinical trials (RCTs) with contrasting results. AREAS COVERED: The present Drug Discovery Case History analyzes the failures of RCTs of solanezumab on AD. Furthermore, the authors review the pharmacokinetics, pharmacodynamics, and tolerability effect of solanezumab from preclinical studies with its analogous m266 in mice. Finally, they describe the RCTs with cognitive, cerebrospinal fluid and neuroimaging findings in mild-to-moderate AD (EXPEDITION studies) and in secondary prevention studies (A4 and DIAN-TU). EXPERT OPINION: Solanezumab was one of the first anti-Aß monoclonal antibodies to be tested in preclinical and clinical AD showing to reduce brain Aß level by acting on soluble monomeric form of Aß peptide without significant results on deposits. Unfortunately, this compound showed to accelerate cognitive decline in both asymptomatic and symptomatic trial participants, and this failure of solanezumab further questioned the Aß cascade hypothesis of AD.

The effects of the COVID-19 pandemic on Italian primary school children's learning: A systematic review through a psycho-social lens.

The COVID-19 pandemic drastically affected many areas and contexts of today's society, including school and family. Several studies focused on the worldwide effects of school closures on students' learning outcomes, context, and well-being. However, the data emerging from these studies are often inconsistent and fragmentary, highlighting the need of a comprehensive analysis of the phenomenon. This need is especially urgent for the countries with the most severe school closure, like Italy. This systematic review aims to collect the opinions of parents, teachers, and students on: other dimensions of Italian primary school students affected by school closures, beyond academic performance; hypothetical agreement between the opinions of parents, teachers, and students regarding the different effects of school closures on Italian primary school students; possible differences between the effects of school closures on Italian primary school students and the students in other countries. Our search was conducted using PRISMA 2020 guidelines on Web of Science, Pubmed, Scopus, and EBSCOHost. The results obtained from 34 articles revealed a strong concern on the part of all stakeholders involved in learning during the pandemic, with evident negative effects for Italian school students. The constraint on distance learning led to a drastic change in everyone's routine, and a negative emotional change on the part of young students. Parents and teachers generally considered distance learning to be ineffective for the education of their children and students; they encountered technical-practical difficulties in the use of electronic devices for participation in school activities; overall learning deficits on the part of students, especially in mathematics, as confirmed by INVALSI results were also found. The investigation reveals a condition of shared emotional and academic performance difficulty, and a further challenging circumstance for students previously at risk of marginalization. Further research in this field is paramount to identify new and adequate recovery strategies.