Spinal Muscular Atrophy Drug Discovery Service

Creative Biolabs provides a comprehensive one-stop in vivo and in vitro service for the research of any neurological type of disease. Our team of experienced scientists and technicians will select the optimal solution according to your project to ensure that we promote your project research progress with maximum efficiency.

Overview

Spinal muscular atrophy (SMA) is a severe childhood monogenic disease caused by loss or dysfunction of the gene encoding survival motor neuron 1 (SMN1). SMN protein expression was negatively correlated with SMA disease severity. Pathological symptoms vary greatly. SMA is the most common genetic cause of infant death.

Fig.1 SMA timeline. (Kolb, 2015)

Creative Biolabs' Molecular Mechanisms Studies of SMA

The pathophysiology underlying SMA is a progressive degeneration of motor neurons caused by biallelic loss-of-function mutations in the SMN1 gene on the long arm of chromosome 5. SMN comes in two forms; SMN1 is the main gene responsible for the functional production of SMN protein. SMN2 preferentially excludes exon 7 during splicing, therefore, SMN2 produces only a small number of functional SMN proteins compared to SMN1.

Creative Biolabs' Animal Models of SMA

Mouse models not only allow the dissection of mammalian biological processes and assessment of gene and protein function but also serve as a useful preclinical tool for testing potential therapies. Additional animal models of SMA are also beginning to play an important role in SMA research, including Drosophila and zebrafish, and recent developments suggest that large animal models (e.g., pigs) may be forthcoming.

• SMN2 transgenic Mice

Mice carrying one or two copies of SMN2 (Smn^–/–; SMN2^+/+) are indistinguishable from controls at birth but die before postnatal day 7 (P7), and so are often referred to as the "severe" model. Mice with four or more copies of SMN2 show complete rescue and a normal lifespan, indicating that enhancing SMN2 expression is a potential therapeutic strategy.

• Modifications to the Severe SMN2 Mouse

The introduction of a second transgene, containing human SMNDΔ7 cDNA, into the severe model extends the lifespan from 6 to 13 days. Many other transgenes (A2G, A111G) containing SMN1 point mutations have also been introduced into severe models, resulting in increased longevity.

Fig.2 Genetics and therapeutic developments of SMA. (Parente, 2018)

Creative Biolabs' One-stop Shop Services for SMA Preclinical Drug Discovery

• In Vitro Services
• In Vivo Services
• Ex Vivo Services
• Discovery Services
• Development Services

Creative Biolabs' goal is to commercialize its proprietary technology and engage with one or more corporate partners in the biopharmaceutical industry. With our expertise and extensive experience in the field of neurology, we can help you answer key questions during your project. If you are interested in our services for SMA research, please feel free to contact us for more.

References

1. Kolb S, J.; Kissel, J.T. Spinal muscular atrophy. Neurologic clinics. 2015, 33(4): 831-846.
2. Parente, V.; Corti, S. Advances in spinal muscular atrophy therapeutics. Therapeutic advances in neurological disorders. 2018, 11: 1756285618754501.