Tissue-engineered skin model of ALS to accelerate biomarkers and drug discoveries
Many specific skin changes have been repeatedly reported in ALS patients, but never as yet fully explained. Such skin manifestations have never been studied systematically due to a lack of proper modeling and in-depth analysis at different levels to confirm and validate results. We have therefore developed a unique artificial skin model, generated in a cell culture dish and derived directly from patients. This novel skin model represents a renewable source of human tissue, quickly and easily accessible (as opposed to brain tissue), to facilitate the identification of biological markers, which will be useful to diagnose the disease prior to clinical symptoms, and to monitor the disease and the effectiveness of experimental treatments. This type of biological tool, directly derived from patients and entirely made of human tissue, has never been described in ALS.
Hence, the aim of our project is to fully characterize our unique in-vitro skin model to address the relationship between skin changes and ALS. Furthermore, this study will accelerate the identification of biomarkers of disease progression that can be detected before neurological symptoms in easily accessible non-neuronal tissue such as skin. An early diagnostic will enable earlier treatments that will be benefic to save motor neurons from degeneration.
Relevance to the acceleration of therapeutics for neurodegenerative diseases of aging
Formal diagnosis of ALS is based on clinical assessment of related symptoms, which appear late in the disease course after degeneration of a significant number of motor neurons. As a result, the identification and development of disease-modifying therapies is difficult. Novel strategies for early diagnosis, to monitor disease progression and to assess response to existing and future treatments are thus urgently needed. Interestingly, many skin changes that often precede the onset of neurological symptoms have been repeatedly reported in ALS patients, but never as yet fully explained. The exploitation of biomarkers of neurodegeneration in a non-neuronal context will pave the way for biomarker-driven therapeutic discovery.
This new model will allow us to perform a variety of different tests and comprehensive analysis using the same skin substitute throughout experiments in order to better understand this interesting relationship between skin changes and ALS.
Conceivably, the application of our ALS-derived skin model may facilitate early diagnosis and help monitor disease progression. It will certainly increase our knowledge of ALS biology and will help accelerate transformational research. This proposed research will be instrumental in improving disease prediction outcomes and will therefore have direct implications not only in ALS but also in neurodegenerative diseases in general.