Biomarkatzaile molekularrak Alboko Esklerosi Amiotrofikoaren diagnostikoan

Abstract

Amyotrophic lateral sclerosis (ALS) is a heterogeneous and incurable neurodegenerative disease. Upper and lower motor neuron degeneration and lateral spinal cord sclerosis are the main histopathologic hallmarks. Despite the great variability in clinical manifestations, general weakness, fasciculations, and spasms occur in all cases due to motor neuron degeneration and muscle atrophy, and this is accompanied by behavioural and cognitive alterations as a result of extensive brain damage. Genetic mutations influence the two main types of the disease: sporadic ALS and familial ALS. Among the identified implicated genes, the main ones are C9orf72, SOD1, TARDBP and FUS, although these genes only explain 15% of sporadic ALS cases and 66% of familial ALS. Current treatments aim to slow down symptoms, and existing pharmacological therapies are scarce and of low efficacy, mainly because the disease is diagnosed too late. In fact, the scales for the diagnosis and monitoring of the severity of ALS are based on the assessment of symptoms and signs, which are expressed when neuronal damage has already occurred. Therefore, it is urgent to find specific and reliable biomarkers for the early diagnosis of ALS. To date, the most studied biomarkers in biological fluids and that have given the most solid results are the proteins derived from the C9orf72 gene, the variants of the TDP-43 protein and the neurofilament subunits. However, various studies have also highlighted the importance of inflammatory and metabolic markers as diagnostic biomarkers for ALS. Definitive biomarkers that allow differential diagnosis, stratification and monitoring of ALS, have not been found yet, and the evidence shows the combination of biomarkers will be necessary. In any case, in order to find new biomarkers, additional research is required to help understand the disease itself, since ALS is the product of numerous interaction mechanisms and we are far from fully understanding the etiopathogenesis and pathophysiology of the disease.