Disease Models

Overview

Disease models play a crucial role in understanding and studying complex disorders like Amyotrophic Lateral Sclerosis (ALS). These models, often developed in laboratory settings, aim to mimic key aspects of the disease to investigate its mechanisms, test potential therapies, and deepen our understanding of pathological processes.

• Mouse Models: The initial laboratory model for ALS, centered on a known genetic cause, involved mice carrying the human gene for mutant SOD1. This mouse model remains the most extensively employed for studying the disease. Rodent models, particularly mice, play a crucial role in testing potential therapies due to their more extensive and intricate nervous systems compared to other animal models. Recently, various rodent models based on familial ALS genes, including TDP43, FUS, and C9ORF72, have been established. There are ongoing developments of mouse models integrating the newly discovered NEK1 gene. All of these models are anticipated to facilitate rapid advancements in uncovering novel approaches to ALS treatment.
• Zebrafish Models: Zebrafish share similar developmental and anatomical features with humans. Researchers can introduce mutated ALS-associated genes into zebrafish to study the effects on motor neuron development and function.
• Drosophila Models (Fruit Flies): Fruit fly models are used for their genetic simplicity and rapid reproduction. When specific ALS-associated genes are incorporated into the genetic makeup of fruit flies, discernible effects emerge, including alterations in fly locomotion and the development of an eye phenotype known as "rough eye," a characteristic feature associated with neurodegeneration.
• Cell Models: Cell lines, often derived from human or mouse cells, are used to study specific aspects of ALS pathology. These models are valuable for high-throughput screening of potential drug candidates.
• Induced Pluripotent Stem Cells (iPSCs): iPSCs are generated by reprogramming adult cells into an embryonic stem cell-like state. Patient-derived iPSCs allow researchers to study ALS using human cells, providing a personalized approach to understanding disease mechanisms and testing potential therapies.