Perspectives and Opportunities for ALS in the “Omics” Era

Dear Colleagues,

Amyotrophic lateral sclerosis (ALS) is an invariably lethal neurodegenerative disorder characterized by the progressive loss of motor neurons. Despite considerable scientific efforts and significant progress over the last decades, many aspects of the underlying pathogenic mechanisms remain unresolved, and no effective therapy is available yet.

Genetic factors are recognized to play a relevant role in ALS, and the recent outbreak of high-throughput genetic analysis techniques has led to the identification of a new series of genes claiming some association with ALS. Nonetheless, the genetic architecture of ALS appears to be complex, and variants of currently known genes account for only a fraction of the estimated heritability of ALS, explaining 40%–80% of familial ALS, but only 5%–15% of sporadic ALS.

The whole scenario is further complicated by the fact that several genes involved in ALS may also be primarily responsible for other neurological and non-neurological conditions. ALS itself has heterogeneous clinical presentation, with varying involvement of the central nervous system and multiple pathophysiological mechanisms that must be taken into account.

In this Special Issue, we aim to gather together both the extensive reviews and innovative research that explore the changing landscape of ALS diagnosis and therapy in the current era of fast-growing molecular investigation methods. Proposed topics include, but are not limited to, the following aspects:

• ALS-related genes and their possibly diverse roles in determining or modifying different ALS clinical presentations and other associated diseases;
• New strategies for the identification and pathogenic assessment of genetic factors underlying ALS, specifically considering the contribution from high-throughput sequencing methods;
• Interactions between genetic and environmental factors in the etiopathogenesis of ALS. Scientific approaches for the identification and validation of such risk factors based on the availability of large datasets from high-throughput genotyping studies (e.g., Mendelian randomization);
• The role of “omics” technologies (from transcriptomics to proteomics, from microbiomics to pharmacogenomics, etc.) in untangling the genetic architecture of ALS, the underlying pathophysiological processes, the nosology, and the relationship between ALS and other neurological conditions with a partially shared basis (including, for instance, frontotemporal dementia);
• The definition of reliable biomarkers to detect ALS at the early disease stage, to help with differential diagnosis and, moreover, to provide a useful tool for stratifying and monitoring patients with ALS in clinical trials;
• The development of innovative therapeutic strategies tailored to ALS patients’ individual genetic makeup in view of the rapidly developing field of personalized medicine;
• Future perspectives and opportunities in ALS research as a consequence of the implementation of new approaches based on the various “omics” technologies.

Dr. Giuseppe Marangi
Dr. Serena Lattante
Guest Editors

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• Amyotrophic lateral sclerosis
• ALS pathophysiology
• Biomarker
• Genomics
• High-throughput genetic analysis
• Missing heritability
• Oligogenic inheritance
• Environmental risk factors
• Polygenic risk
• Personalized medicine