Exploring Model Systems in Amyotrophic Lateral Sclerosis Research
Amyotrophic Lateral Sclerosis (ALS), also known as Lou Gehrig's disease, is a devastating neurodegenerative disorder characterized by the progressive degeneration of human motor neurons in the brain and spinal cord. Despite significant advancements in understanding ALS pathology, the lack of effective treatments remains a significant challenge.
Fig. 1 ALS pathophysiology, genetic causes and risk factors.1
Creative Biolabs delves into the intricate world of ALS research, focusing on the indispensable role of in vitro and in vivo models in elucidating disease mechanisms, screening potential therapeutics, and advancing drug discovery efforts. We will explore the strengths and limitations of various model systems, shedding light on their contributions to ALS research and highlighting recent innovations and emerging trends.
As a partner, we offer the following related services to help accelerate the progress of your ALS program.
| Our Services | Descriptions |
| ALS In Vitro Assay | Creative Biolabs offers cutting-edge in vitro assay services specifically tailored for ALS research, providing invaluable insights into the underlying mechanisms of the disease and potential therapeutic strategies. |
| ALS Biomarker Assay | Creative Biolabs has established a professional biomarker testing team dedicated to providing our clients with specialized ALS biomarker testing to help screen potential ALS biomarkers or detect identified ALS biomarkers. |
| ALS Drug Discovery | Creative Biolabs provides one-stop solutions for ALS research that may lead to a better understanding of ALS, advance ALS research, and develop promising new therapies. We want to contribute to better health in the world by developing and offering user-friendly solutions and products. |
The Importance of Model Systems in ALS Research
ALS is a devastating neurological disorder characterized by the progressive degeneration of motor neurons, leading to muscle weakness, atrophy, and eventually death. Model systems serve as indispensable platforms for investigating the intricate mechanisms underlying ALS pathology.
- They allow researchers to dissect molecular pathways, study disease progression, and screen potential therapeutics in a controlled environment.
- These models provide valuable insights into the heterogeneity of ALS, which manifests clinically with varying degrees of motor neuron degeneration and extramotor involvement.
- By faithfully mimicking aspects of ALS pathology, model systems enable researchers to interrogate disease mechanisms across different biological scales, from individual cells to entire organisms.
Researchers rely heavily on model systems to simulate the disease condition in a controlled environment, paving the way for an understanding of the disease's pathogenesis and the progression, and potentially devising targeted treatments. Thus, model systems indubitably form the backbone of ALS research, providing insights into disease mechanisms and facilitating the testing of intervention strategies.
A number of cell models are important tools commonly used in ASL research. You can browse the table below to see a list of our recommended products.
| Cat. No | Product Name | Species | Cell Types |
| NCL-2101-ZP36 | iNeu™ Human Motor Neuron Progenitors- Amyotrophic Lateral Sclerosis (ALS) (C9ORF72 expansion) | Human | Motor Neuron |
| NCL-7P001 | iNeu™ Motor Neurons ALS TDP43 Q331K, Disease Model | Human | Motor Neuron |
| NCL-7P002 | iNeu™ Motor Neurons ALS TDP43 M337V, Disease Model | Human | Motor Neuron |
| NCL-7P004 | iNeu™ Motor Neurons ALS TDP43 Q331K Kit, Disease Model | Human | Motor Neuron |
| NCL-7P005 | iNeu™ Motor Neurons ALS TDP43 M337V Kit, Disease Model | Human | Motor Neuron |
| NCL2110P231 | FUS/TLS Stress Granules Assay Cell Line [Amyotrophic Lateral Sclerosis (ALS) Model] | Human | Stable Cell Line |
| NCL2110P236 | TDP-43 Stress Granules Assay Cell Line [Amyotrophic Lateral Sclerosis (ALS) Model] | Human | Stable Cell Line |
| NRZP-0323-ZP8 | iNeu™ Glutamatergic Neurons TDP-43 M337V/WT, ALS Model | Human | Glutamatergic Neuron |
| NRZP-0323-ZP10 | iNeu™ Glutamatergic Neurons MAPT P301S/WT, ALS Model | Human | Glutamatergic Neuron |
| NRZP-0323-ZP14 | iNeu™ Glutamatergic Neurons PRKN R275W/R275W, ALS Model | Human | Glutamatergic Neuron |
| NRZP-0323-ZP42 | iNeu™ Human iPSC, ALS SOD1 H44R, Fibroblast-derived | Human | iPSC |
| NRZP-0323-ZP45 | iNeu™ Human iPSC, ALS, PBMC-derived | Human | iPSC |
| NRZP-0323-ZP46 | iNeu™ Human iPSC, ALS C9orf72 HRE, PBMC-derived | Human | iPSC |
| NRZP-0323-ZP59 | iNeu™ Human iPSC, ALS TDP-43 N390D, PBMC-derived | Human | iPSC |
In Vitro Assays For ALS Models
In vitro neuronal models have been a gold standard in ALS research, offering a reductionist approach to studying the intricacies of cellular and molecular processes associated with motor neuron degeneration. The use of animal cells, including primary neuron cultures, stem-cell-derived neurons, and cell lines facilitate a detailed exploration into the course of motor neuron diseases.
| Models | Descriptions |
| Primary cultures | Primary cultures of motor neurons derived from rodent or human embryonic stem cells allow researchers to investigate the molecular underpinnings of neuronal dysfunction and death in ALS. These cultures can be subjected to various stressors, such as excitotoxicity or oxidative stress, to mimic pathological conditions observed in ALS patients. |
| iPSC-derived neurons | Advances in iPSC technology and reprogramming technology have enabled the generation of patient-specific motor neurons, providing a personalized platform for studying genetic forms of ALS and screening potential therapeutics. |
| Non-neuronal cells | In vitro models incorporating non-neuronal cells, such as astrocytes and microglia, have shed light on the role of glial dysfunction in ALS pathogenesis. Co-culture systems allow for the examination of cell-cell interactions and the propagation of pathological processes within the central nervous system microenvironment. High-throughput screening platforms utilizing automated microscopy and image analysis have facilitated the discovery of novel drug candidates targeting various aspects of ALS pathology, including protein aggregation, mitochondrial dysfunction, and neuroinflammation. |
By recapitulating essential aspects of the molecular pathology of ALS, these in vitro assays provide an invaluable platform for studying gene expression, protein aggregation, intracellular trafficking, cellular metabolism, and neuronal and non-neuronal cell interactions.
In Vivo Models for ALS
In vivo models remain indispensable tools for ALS research, offering the complexity of a living organism and the ability to assess disease progression in a physiological context. Several genetically-engineered models of ALS, typically harbouring mutations in genes known to cause human ALS, such as
- SOD1
- TDP-43
- FUS
- C9ORF72
| Models | Descriptions |
| Caenorhabditis elegans and Zebrafish | The anatomical transparency of C. elegans and Zebrafish enables visualization of neurons and monitoring of neuronal activity over time using co-expressed fluorescent proteins. |
| Drosophila melanogaster | Drosophila melanogaster is an easy-handling and cost-effective animal model with a short lifespan and complete genome sequencing. They are widely used for studying neurodegenerative diseases including ALS. |
| Rodents | Transgenic rodents are the most used animal models and provide important insights into pathogenesis. Rodent models have been widely used in ALS research since the first SOD1 (A4V and G93A) ALS mouse models were developed in 1994. Although rats are used much less than mice, they also have physiological characteristics like those in humans and the possibilities for genetic manipulation are historically more recent in rats than in mice. |
| Canine models | Considering the clinical and molecular similarities between idiopathic CDM and SOD1-ALS, studies of canine idiopathic CDM may help better dissect the pathological mechanisms of ALS. |
| Swine models | The swine model has been widely used to study human disease pathology because of its anatomical, physiological, and biochemical similarities with humans, including high similarities in the genome and neuropsychiatric disease characteristics. Currently, several neurodegenerative diseases have been recapitulated in pigs, including ALS (TDP-43-related and SOD1-related). |
| Non-human primate models | Non-human primate models have anatomical, physiological, and biochemical characteristics relevant to humans, including high genomic similarity. However, similar as pig models, the non-human primate models of neurodegenerative diseases have limitations of high cost and ethical issues. |
These models recapitulate key features of ALS pathology, including protein aggregation, axonal degeneration, and gliosis, providing valuable insights into disease progression and potential therapeutic targets.
Moreover, advances in genome editing technologies, such as CRISPR-Cas9, have facilitated the generation of precise genetic modifications, allowing for the development of new ALS models with enhanced fidelity to human disease.
Future Directions for Model Development
The future of model development for ALS research holds promise, with the increasing sophistication of model systems.
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One promising approach is the development of organoid models derived from patient iPSCs, which recapitulate the cellular diversity and architecture of the human central nervous system.
- These three-dimensional cultures allow for the study of cell-cell interactions and disease propagation in a more physiologically relevant context.
- Furthermore, the integration of multi-omics technologies, such as transcriptomics, proteomics, and metabolomics, promises to provide a comprehensive understanding of ALS pathogenesis and identify novel therapeutic targets.
- Innovative approaches to in vivo modeling are emerging, such as the use of zebrafish and Drosophila, providing lower-cost, high-throughput platforms for disease modeling and drug screening. The continued refinement of animal models, including the generation of non-human primate models of ALS, holds promise for bridging the gap between preclinical research and clinical translation.
From in vitro assays to in vivo mouse models, each system offers unique insights into disease mechanisms and therapeutic targets. By harnessing the power of diverse model systems and embracing emerging technologies, researchers can accelerate progress towards a future where ALS is no longer a fatal diagnosis.
Creative Biolabs, with its roots grounded in a deep understanding of ALS and the molecular processes involved, leverages both in vitro and in vivo models. Our insightful approach equips us to forge solutions that unravel the disease's circuitry.
References
- Mead, Richard J., et al. "Amyotrophic lateral sclerosis: a neurodegenerative disorder poised for successful therapeutic translation." Nature Reviews Drug Discovery 22.3 (2023): 185-212.
- Zhu, Longhong, et al. "Pathological insights from amyotrophic lateral sclerosis animal models: comparisons, limitations, and challenges." Translational Neurodegeneration 12.1 (2023): 46.
