New insights in early diagnostic and prognostic clinical, instrumental, and fluids biomarkers in Amyotrophic Lateral Sclerosis

Rationale of my PhD Thesis- Amyotrophic Lateral Sclerosis (ALS) is a devastating neurodegenerative disease that provoke huge disability and shows a fatal exitus. No real cure exists, despite sizeable efforts have been done during the last two decades. Moreover, the onset of bulbar and respiratory impairments represents a frightful event since it is associated with a shorter survival and a worst quality of life. The need to identify easily accessible, reproducible, and non-invasive biomarkers is crucial for enabling early disease diagnosis and, consequently, initiating available therapies as early as possible to slow down its progression. Simultaneously, there is a requirement for biomarkers capable of stratifying patients based on the risk of developing bulbar and/or respiratory impairments. This stratification allows for the early implementation of potential prophylactic therapies to slow the onset of these symptoms and provide accurate behavioral guidelines to patients. Furthermore, it is essential to identify prognostic biomarkers that enable both clinicians and patients to understand the disease's progression in the subsequent months/years and better select patients for enrollment in clinical trials. Predictive biomarkers of treatment response are also necessary, complementing the clinical scales currently used in clinical trials. Building upon these premises, in the course of my doctoral research, I have sought to identify novel diagnostic and prognostic clinical, instrumental and fluids biomarkers. I’m going to show you results obtained during these four years of PhD course. My thesis is divided in 2 sections: in the first I’m presenting the results of studies I led in which I wanted to find out new clinical, instrumental and bio-humoral biomarkers with the aim of early identification of bulbar and respiratory impairment, while in the second part I’m presenting results of novel fluid biomarkers, some of them are still preliminary data.