The Relation between ALS and the Skin: A Novel Human In Vitro Model to Identify New Biomarkers

Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease affecting the motor neurons of the brain and spinal cord causing progressive paralysis and death [1]. ALS patients develop progressive muscle weakness, atrophy, then paralysis and death within 3 to 5 years after the onset of the disease [1,2]. Close to 90% of all ALS cases are sporadic (SALS) while the other 10% represent familial ALS (FALS) [3]. ALS diagnosis is actually based on clinical assessment of related symptoms [4]. As a chronic progressive disease, ALS has a presymptomatic period during which the pathological process begins, but motor signs required for the clinical diagnosis are absent. This particularity makes the development of disease-modifying therapies for ALS very difficult as the range, being from 8.0 to 15.6 months between the first symptoms and the diagnosis, is quite long [4]. At this late stage in the development of the disease, numerous motor neurons have already died or gone through degeneration process. The identification of biomarkers in ALS has been a very active area of investigation, employing transcriptional studies, protein profiling in blood and CSF, imaging, and electrophysiological techniques. While these techniques have identified some potential ALS biomarkers, so far none have proven to be clinically useful. Therefore, the discovery of specific biomarkers for ALS is of great importance to help facilitate early diagnosis of the disease as well as monitoring its progression and assess response to existing and future treatments. Both skin and neural tissue come from the same germ layer known as the ectoderm. ALS, as well as other neurodegenerative diseases, are often accompanied by skin changes that appear before the appearance of neurological symptoms [5]. The non-cell autonomous toxicity in ALS has been