Drosophila: An Emerging New Approach Method (NAM) for Studying Amyotrophic Lateral Sclerosis (ALS).

Drosophila melanogaster (D. melanogaster), or fruit flies, are a commonly used model organism in the study of neurodegenerative diseases (NDs). Their short lifespan, low cost, genetic tractability, and conserved signaling and developmental pathways make them ideal for studying NDs and associated biochemical pathways. Further, flies offer the advantage of high-throughput exploratory drug and genetic screening without stringent ethical constraints. Therefore, D. melanogaster serves as an ideal organism for preliminary drug screening before transitioning to toxicity and efficacy studies in vertebrate models. Following the recent plan by the United States FDA (US FDA) and the National Institutes of Health (NIH) to progressively phase out preclinical drug testing in vertebrate animals and introduce New Approach Methodologies (NAMs), D. melanogaster has the potential to become part of the conventional drug testing pipeline in the future. This literature review focuses on the use of D. melanogaster models as a powerful, low-cost model organism to study superoxide dismutase 1 (SOD1)- and TAR DNA-binding protein 43 (TDP-43)-linked Amyotrophic Lateral Sclerosis (ALS), as well as previous efforts to screen drugs in SOD1- and TDP-43-expressing Drosophila models.