|
Description
|
Neurodegenerative diseases are common and have major familial and socio-economic impact in modern societies. Amyotrophic lateral sclerosis (ALS) is the most devastating one, characterized by rapidly progressive paralysis and death from respiratory failure. The ALS clinical spectrum includes very heterogeneous phenotypes. Thus, diagnosis delay is considerable and prognosis quite variable. There is clearly a need for a biomarker to support early diagnosis and prognosis as it would allow timely referral and treatment intervention with influence on survival. It would also be essential to stratify patients in clinical trials, increasing the chances of finding an effective drug. Several putative biomarkers of ALS have evaluated especially in cerebrospinal fluid but, as they require invasive methods, are not useful for routine screening. This project aims to take a step forward by providing a minimally invasive blood-based biomarker. Recent evidence indicates that deregulation of microRNAs (miRNA) is involved in ALS pathogenesis. Several ALS-related proteins are involved in biogenesis of miRNAs and tissue-specific expression of miRNAs suggests that disrupted expression of pathogenic miRNAs may be targeted by miRNA-based therapeutics. Importantly, miRNAs are exceptionally stable and found in the plasma and serum. The project?s overall goal is to identify a set of miRNAs that can be used as biomarkers to support diagnosis and prognosis, with application in clinical trials. The hypothesis is that different phenotypes and disease stages are associated to different miRNA profiles, involved in the neurodegeneration process. This predicts that such identification will open new windows to treatment strategy. The aim is to assess differences in miRNA expression levels between ALS patients, healthy controls and patients with other mimicking neuromuscular diseases. The combination of miRNA signatures with sophisticated clinical phenotyping will allow the optimization of biomarkers for subsets of ALS patients (personalized medicine). The follow up samples will enable evaluating the dynamic of miRNA expression related with disease burden and progression, a critical step to the development of automatic prognostic methods. The added-value of this study rest on the number of available patients? samples with detailed clinical, respiratory and neurophysiological data and the direct interaction with projects that are developing new integrative mining algorithms needed to meaningfully interrogate and interpret such datasets. Also, the team has large experience and knowledge on ALS; has collaboration experience with international consortiums and has expertise in the intellectual exploitation and direct valorization of results. The scientific contributions will have strong effect in healthcare sustainability and ultimately impact on health ageing. As such, the expected impact is both social and economic. This model could be replicated in other neurodegenerative diseases.
|
