Amyotrophic Lateral Sclerosis (ALS) Model based In Vitro Assay Services

Amyotrophic Lateral Sclerosis (ALS) is the most common form of motor neuron disease, characterized by progressive degeneration of nerve cells in the nervous system. Creative Biolabs offers both standard and customized in vitro, in vivoand ex vivo services tailored for ALS research.

Available Models Available Assays

Available In Vitro Models

Fig. 1 Representative images detecting FUS cytoplasmic mislocalization. Fig.1 Detection of FUS cytoplasmic mislocalisation.¹

Cell models	Details
ALS Patient-Derived iPSCs	Primary cells from ALS patients are collected and converted into iPSCs, which can then be differentiated into end-point cells, including motor neurons. Due to their ability to rapidly proliferate while retaining the genetic and epigenetic markers associated with ALS, these cells are optimal for high-throughput screening of small molecule libraries or functional genomics-type approaches using high-content imaging or biomarker readouts.
In Vitro Co-Culture Models	iPSCs or NPCs from ALS patient-derived motor neurons and glial cells are used to build our brain-like environment for ALS patient-derived neural cells that better mimics in vivo conditions. Compared to the monoculture, the co-culture model provides additional critical insights for key parameters, such as neuroinflammation, neurodegeneration, etc.
Spinal Cord Cell Cultures	Primary cultures of embryonic rodent spinal cords can be utilized to examine motor neuron development, function, and degeneration in a controlled setting.
Organotypic Cultures	Organotypic cultures of spinal cord slices: This technique preserves the cellular content and the spatial organization of cells in the spinal cord by maintaining tissue slices in culture. As a result, this model can provide data comparable to in vivo investigations, while avoiding the extended timelines associated with typical in vivo experimentation. Neuromuscular Organoids (NMOs): NMOs self-organizes into distinct spinal nerve and skeletal muscle regions and maintains them as 3D structures for months. This organoid is the latest technology in ALS in vitro research, providing the richest and most accurate readouts.
Motor Neuron Cell Line	NCS-34: This cell line is a motor neuron-like hybrid of mouse spinal cord and neuroblastoma, expressing the characteristics of motor neurons. In ALS research, it is a popular choice for experimentation involving excitotoxicity, oxidative stress, or the addition of ALS-associated mutant proteins. SH-SY5Y: SH-SY5Y cells are derived from human neuroblastoma, they can be used to study the pathogenesis of ALS. SH-SY5Y cells support high-throughput screening assays when exposed to ALS-associated stressors. It is an efficient tool to screen large libraries of compounds for their potential neuroprotective effects with a human-derived cell line background. FUS/TLS Cell Line: The FUS/TLS Cell Line allows for analytical assessment of the endogenous formation of stress granules in living cells. This model can also be used to monitor FUS/TLS protein distribution in living cells, study protein localization patterns, and quantify intracellular aggregation. TDP-43 Cell Line: This cell line is composed of the U2OS cell line modified to stably express fluorescently tagged TDP-43. TDP-43 plays a critical role in ALS pathology because it delocalizes to, and aggregates in, the cytoplasm under disease conditions. These characteristics make this cell line the ideal choice for high-content screening. Cell engineering and customization: We also offer services for generating new disease models tailored to your unique research goals.

Available Assays

Utilizing our expertise and the models described above, we have developed a series of assays for use in ALS research. Through rigorous internal testing, we assure high quality quantitative and qualitative data, allowing for precise assessment of therapeutic interventions.

Protein Aggregation and Delocalize.

ALS-associated Protein Aggregation Assay: Determines the presence of aggregated proteins and qualify/quantify the amount of aggregation, including mutant SOD1, TDP-43, FUS, and C9orf72.

A hallmark of ALS is dysregulation of nucleocytoplasmic transport. We offer several readouts for measuring localization, including blotting, live-cell imaging, confocal microscopy and more. Using our decades of expertise, we can work with you to select the relevant targets and readouts for your project.

Stress Granule Formation Assay	C9orf72 RNA Foci Formation Assay
C9orf72 Di-peptide Aggregation Assay	Nucleo-cytoplasmic Transport Assay
TDP-43, FUS, SOD1 Localization & Aggregation Assay	ALS High-Throughput Phenotypic Screening Assay
ALS Therapeutic Target Characterization	Nucleo-cytoplasmic Transport Assay

Motor Neuron Health and Viability

Cell Viability Assay: Creative Biolabs offers a range of cell viability assays based on reduced neuronal activity, metabolic activity, cellular ATP production, and/or live-cell imaging to support your projects.

Neurite Length and Branching: This assay measures motor neuron projection length and complexity under conditions of interest, which is indicative of neuronal development and function.

Neuronal Excitability and Electrophysiology

Electrophysiological Recordings: Our electrophysiology platform provides valuable insight into neuronal health and activity by monitoring the potential and current across the membrane of a neuron. This assay can help evaluate neuronal health and function under disease conditions or following treatment with a compound of interest.

Microelectrode Array (MEA) Assay: Microelectrode arrays (MEAs) are ideal for assessing neuronal health and activity across a population of neurons. MEA allows simultaneously measures multiple parameters, including mean firing rate, spike rate, burst duration, synchronicity, and more. Compared to traditional electrophysiology methods like voltage clamp recording, MEA provides insight into the relationships between neurons under disease or treatment conditions by monitoring many cells at once.

Through our high-quality assays and expert consulting, we at Creative Biolabs are committed to supporting researchers in unraveling the complexities of ALS pathology, enhancing the drug discovery, and facilitating effective treatments for ALS.

For consultations and inquiries, please feel free to contact us for more information.

Reference

Oyston, Lisa J., et al. "Rapid in vitro quantification of TDP-43 and FUS mislocalisation for screening of gene variants implicated in frontotemporal dementia and amyotrophic lateral sclerosis." Scientific Reports 11.1 (2021): 14881. Distributed under Open Access license CC BY 4.0, without modification.

For Research Use Only. Not For Clinical Use.

Related Section

SG Formation Assay

C9orf72 RNA Foci Formation Assay

C9orf72 Di-peptide Aggregation Assay

Nucleo-cytoplasmic Transport Assay

TDP-43, FUS, SOD1 Localization & Aggregation Assay

ALS High-Throughput Phenotypic Screening Assay

ALS Therapeutic Target Characterization