Projects

CRESLA researchers are originators and managers of several national and international research projects aimed at expanding and improving our knowledge about ALS. Listed below are some of the current research projects

Internationals:

• Azygos: a large proportion of unidentified inherited cases in ALS patients is due to under-recognition of recessive cases in most genetic studies performed to date. The Azygos project aims to perform a Whole Genome Sequence (WGS) study on a cohort of 96 consanguineous patients of Italian descent to identify novel autosomal recessive causative genes.

• BRAINTEASER (BRinging Artificial INTelligencE home for a better cAre of ALS and Multiple Sclerosis), Horizon 2020: a study focused on the use of artificial intelligence, particularly low-cost sensors and apps, designed to supplant the technical, medical, psychological and social needs of ALS patients. The BRAINTEASER (BRinging Artificial INTelligencE home for a better cAre of ALS and Multiple Sclerosis) project aims to integrate social, environmental and clinical data to develop models of patient stratification and progression that can address the needs of preventive medicine and risk prediction.

Nationals:

• InitiALS: INITIALS is a project with the aim of identifying gene-environment interactions underlying the development of the disease. It will be based on a multidimensional (genetic, methylomic, clinical, and environmental) dataset created from a cohort of ALS patients residing in Piedmont.

• Progetto di ricerca finalizzata 2019: study aimed to evaluate the correlation between clinical-functional involvement (considered as cumulative set of body regions affected by the disease, predominantly affected side, first and second motor neuron signs), neuropsychological assessment, genetic and neuroimaging features at diagnosis, subsequent regional spread patterns during disease progression, and their correlation with overall survival in an ALS patient population.

• Progetto di ricerca finalizzata 2020 (Project in collaboration with the M. Negri Pharmacological Institute of Milan): the formation of toxic protein aggregates in the nervous system of ALS patients is a well-known event; the TDP-43 protein has been found to be one of the main components of these aggregates. This study aims to understand how acetylation processes, especially those involving the enzyme called Cyclophilin A, lead to the formation of TDP-43 protein aggregates. The cell model used to conduct these investigations is circulating lymphomonocytes of obtained from blood samples of patients.

• EvTestinALS is a national multicenter project, sponsored by the University of Trento, CIBIO Department and funded by AriSLA Foundation, whose aim is to analyze plasma extracellular vesicles in ALS and their role in predicting disease progression. Contextually, this project will evaluate the reliability of measuring plasma extracellular vesicle parameters against what can be detected centrally, particularly by comparing the characteristics of these vesicles in CSF versus plasma.

• PERMEALS (PNRR-MAD-2022-12375731) is a national multicenter project funded by the Ministry of Health through European Union funds allocated for the NRP. The goal of this project is to characterize phenotypic heterogeneity in ALS using a multidimensional approach that considers clinical, neurophysiological, neuropsychological, neuroimaging data, biological biomarkers, genetic risk factors, and their impact in cellular models. Data collected as part of this project will be analyzed using machine learning approaches in order to maximize the probability of identifying variables associated with phenotype and biomarkers, as well as novel genetic susceptibility factors for ALS development.

• DRIVEALS (PNRR-RF-2021-12374238) is a national multicenter project sponsored by the Auxologico Institute in Milan and funded by the Ministry of Health through European Union funds allocated for the PNRR.This project exploits a highly integrated approach with the goal of correlating (using machine learning techniques) the profile of ALS-associated genetic factors with neurochemical biomarkers, neuroimaging data, neurophysiology data, neuropsychological profile and, finally, with the phenotypic profile of individual ALS patients.Contextually, the collected data will be analyzed with the aim of obtaining in-depth phenotypic characterization and genetic characterization by exploiting this integration of clinical, genetic and neurochemical data.

• Impiego della biopsia di cute per la ricerca di biomarcatori nella Sclerosi Laterale Amiotrofica: is a single-center study, sponsored by CRESLA and the University of Turin, funded by Fondazione Cassa di Risparmio di Torino, which aims to investigate whether skin biopsy can provide useful information for diagnosis and prognosis definition in ALS patients.Skin biopsy data from ALS patients will be compared with clinical, laboratory, including biological biomarkers, and instrumental characteristics, as well as with the results of skin biopsies taken in healthy subjects and those with other neurological diseases.

• SPECTRALS is a national multicenter study, sponsored by Milano-Bicocca University and the COMiB research center, whose aim is to identify FTIR/Raman spectroscopic and biomolecular markers of ALS by analyzing tear fluid. In addition, this study allows for a deeper understanding of the pathogenetic mechanisms of ALS through the application of vibrational spectroscopy and high-resolution mass spectrometry methods.