Sesto Fiorentino

Researchers are investigating the spectrum of amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD), two related neurodegenerative diseases that can occur together and share clinical, genetic, and pathological features. The study aims to find new biological markers to improve diagnosis and understand disease mechanisms beyond current clinical methods. Experts from neurology, biology, chemistry, physics, and AI are using advanced techniques like transcriptomics, proteomics, and genomics to analyze easily accessible tissues such as cerebrospinal fluid, skin, olfactory mucosa, serum, and tears. The project involves collecting and analyzing samples from patients with different ALS and FTD phenotypes, as well as non-neurodegenerative neurological controls. Various methods will be applied, including next-generation sequencing, protein quantification assays, microfluidic analysis of RNA profiles, immune pathway evaluation, seed amplification assays to detect pathological TDP-43, and microbiota composition analysis. Samples are processed and studied across multiple research centers collaborating closely, with some samples also used for cell biology and protein structure studies. Participants will undergo clinical and neuropsychological assessments and specific smell tests before sample collection. The collected data, including clinical and psychological information, will be analyzed by a specialized data science team to identify disease biosignatures. The primary outcome is to evaluate the accuracy of the seed amplification assay in detecting misfolded TDP-43 over 24 months. This comprehensive approach aims to improve patient classification, monitor disease progression, and support therapeutic evaluation in future clinical trials.

Researchers are studying Parkinson's disease (PD), multiple system atrophy (MSA), and dementia with Lewy bodies (DLB), which are difficult to diagnose early on. These diseases involve distinct misfolded alpha-synuclein proteins that create characteristic brain aggregates, serving as important disease markers. The study aims to improve early diagnosis by detecting and characterizing these protein aggregates using advanced ultrasensitive tests on samples from the olfactory mucosa, blood, and urine. The study uses innovative techniques such as RT-QuIC, Simoa SR-X, ELISA, and NTA to analyze these bodily samples, combined with transmission electron microscopy and nuclear magnetic resonance methods. Researchers will also apply machine learning to integrate clinical data, including tests of smell function, with experimental results. This approach seeks to identify unique biomarker patterns to accurately recognize and stratify patients with PD, MSA, and DLB. Participants will provide samples of olfactory mucosa, blood, and urine for repeated testing to track disease markers over time. Researchers will measure proteins like neurofilament light chain, alpha-synuclein, and synapsin-3, and assess olfactory function to see if it correlates with disease progression. The study aims to develop diagnostic tools for earlier and more precise disease recognition, which could improve patient selection for treatments and clinical trials and support monitoring of disease progression and therapy effects.

Researchers are creating and managing a national Italian database to study patients with hypoparathyroidism or pseudohypoparathyroidism, two rare diseases affecting parathyroid function and calcium balance. The study aims to collect detailed medical, genetic, clinical, and treatment data from a wide group of patients across Italy to better understand these conditions, their prevalence, and incidence. This research will help improve knowledge about different forms of these diseases and support optimal care planning. The study involves 41 specialist centers throughout Italy, including endocrinology and pediatric departments, where patients with these conditions are treated. Data will be gathered both retrospectively from medical records at the time of recruitment and prospectively during follow-up visits over a 10-year period. No new treatments or interventions are administered by the study; instead, information on patients' usual treatments and responses will be collected. Participants will have their medical histories, clinical features, bone health, laboratory results, and quality of life monitored regularly as part of their usual care. The study will assess disease characteristics, bone fragility, and treatment responses over time, aiming for long-term analysis up to 10 years. Data will be collected anonymously and analyzed to improve understanding and management of these rare diseases.

Researchers are creating and managing a national multicenter database to study patients with parathyroid carcinoma or atypical parathyroid adenoma in Italy. These two rare types of parathyroid gland cancers represent about 1% of all parathyroid tumors. The goal is to collect detailed anamnestic, diagnostic, genetic, clinical, histological, and therapeutic information from a wide group of patients to improve understanding and management of these diseases. The study will take place at 33 specialized endocrinology and endocrine surgery centers across Italy, enrolling patients from all 20 regions. It includes two groups: patients with parathyroid carcinoma and those with atypical parathyroid adenoma, both sporadic and genetic cases. Data collection is both retrospective, using existing medical records at the time of recruitment, and prospective, following patients over a 10-year period during their regular clinical visits. The study does not involve any new treatments or interventions but records responses to standard surgeries and medications used in patient care. Participants will be followed through their usual medical visits at recruiting centers, with data collected anonymously and analyzed collectively. Information gathered includes demographics, family history, lifestyle, clinical history, diagnostic imaging and tests, surgery details, histological findings, genetic testing results, post-operative follow-up, and therapy outcomes. The study aims to evaluate the prevalence and incidence of these tumors, differentiate clinical and biological features, and assess therapy responses over short and long terms to inform tailored treatments. The overall participation can last up to 10 years from enrollment.