A-Z™ SMA Drug Discovery Platform

Spinal muscular atrophy (SMA) is a devastating genetic disease that affects the motor neurons in the spinal cord, resulting in progressive muscle weakness and atrophy. SMA is caused by mutations in the survival motor neuron 1 (SMN1) gene, which leads to reduced levels of SMN protein. Currently, there is no cure for SMA, but there are several therapies that aim to increase SMN protein levels. Creative Biolabs' SMA Drug Discovery Platform provides a comprehensive suite of in vitro, ex vivo, and in vivo assays for the development of new SMA therapies.

In Vitro Cell Models

Creative Biolabs' SMA Drug Discovery Platform includes a range of in vitro cell models that mimic the pathophysiology of SMA. These models can be used to study the effects of potential therapeutics on SMN protein expression, motor neuron survival, and muscle function. The most commonly used cell model for SMA research is the NSC34 motor neuron cell line. NSC34 cells express low levels of SMN protein and display many of the characteristics of SMA motor neurons, including axonal degeneration and reduced survival. Creative Biolabs offers a range of NSC34-based assays, including SMN protein quantification, cell viability assays, and neurite outgrowth assays.

In addition to NSC34 cells, Creative Biolabs offers other cell models for SMA research, including primary motor neurons and muscle cells. These cell models can be used to study the effects of therapeutics on different aspects of SMA pathology, such as muscle atrophy and motor neuron degeneration.

Creative Biolabs also offers in vitro assays using patient-derived induced pluripotent stem cells (iPSCs). iPSCs can be differentiated into motor neurons and muscle cells, providing a patient-specific model for studying SMA pathology and drug efficacy.

Fig.1 SMA iPSCs derived motor neurons assay.

Ex Vivo Assays

Creative Biolabs' SMA Drug Discovery Platform also includes ex vivo assays that use tissue samples from SMA patients or animal models. One of the most widely used ex vivo assays for SMA research is the spinal cord slice culture assay. This assay involves culturing thin slices of spinal cord tissue and measuring the survival of motor neurons and the expression of SMN protein. The spinal cord slice culture assay is a powerful tool for studying the effects of potential therapeutics on motor neuron survival in a tissue-specific context.

Fig.2 SMN spinal astrocytes assay.

In Vivo Assay

Once we have identified lead compounds using our in vitro and ex vivo assays, we move to in vivo assays using SMA mouse models. The most commonly used animal model for SMA research is the mouse model, which carries a deletion of the Smn1 gene and displays many of the characteristics of human SMA. Creative Biolabs offers a range of mouse models for SMA research, including severe, intermediate, and mild models.

Creative Biolabs' in vivo assays for SMA research include behavioral assays, such as grip strength and rotarod tests, as well as histological analysis of muscle and spinal cord tissue. These assays can be used to measure the effects of potential therapeutics on muscle function, motor neuron survival, and SMN protein expression in vivo.

Customized Assay Development

Creative Biolabs offers customized assay development to meet the specific needs of individual research projects. This ensures that the most appropriate assays are used to screen for compounds that are most relevant to the specific research question. With our expertise, customization, efficiency, and quality control, we are committed to providing high-quality service to our clients and advancing the field of SMA drug discovery.

Get in touch with us today to find out more about our SMA assay services.

Reference

1. Varderidou-Minasian, Suzy, et al. "Spinal Muscular Atrophy Patient iPSC-Derived Motor Neurons Display Altered Proteomes at Early Stages of Differentiation." ACS omega 6.51 (2021): 35375-35388.