Drug Screening Service for Amyotrophic Lateral Sclerosis

Amyotrophic lateral sclerosis (ALS) is a fatal and untreatable neurodegenerative disease characterized by the degeneration of motor neurons. Many studies have been performed to reveal the genetics and neuropathology of ALS and major advances are acquired, involving the related genes and the models based on advances in understanding the genetics of ALS. As an invertebrate model of ALS, Caenorhabditis elegans is characterized by a fast-growing, transparent body that is amenable to molecular genetic analysis. In contrast to mammalian models, the nematode model is simpler and can contribute to ALS studying as a complementary model. Here we have established the simple organisms, C. elegans, as important models for effectively and inexpensively screening potential ALS drugs and elucidating pathways of drug action.

C. elegans as a model organism for ALS

As a progressive neurodegenerative disease, ALS primarily affects the motor system and presents with progressive muscle weakness. The disease manifests clinically in adulthood and is characterized by the selective degeneration of motor neurons (including lower and upper motoneurons in the spinal cord and cerebral cortex). ALS is a familial disease in ∼10% of patients, whereas approximately 90% developing sporadic ALS (SALS). At present, there are approximately 20 genes associated with ALS, including SOD1, TARDBP, FUS and C9orf72, mutations associated with the most common causes of typical ALS. The major advances in understanding the genetic basis of ALS have made contributions to the construction of different models of this disease. As a model organism, C. elegans has emerged as a powerful tool for large-scale genetic and chemical screens due to a range of advantages. Especially, the characteristics include neurons with most of the known neurotransmitters in the mammalian nervous system, well-characterized synaptic interconnections, visualized neurons with fluorescently labeled in vivo making the nematode an excellent model to study ALS and other neurological diseases. The first C. elegans ALS model is the SOD1 model, which is constructed by introducing human wildtype and ALS-related mutant forms of SOD1 under the control of a muscle promoter. With the depth of research, several other C. elegans ALS models have emerged, such as TDP-43 and FUS/TLS models.

Service offerings

On our platform, we have developed a drug screening system using the dnc-1 KD model together with Multi-Worm Tracker (MWT) to understand the pathological mechanisms of SALS and develop potential therapeutic compounds.

C. elegans model of ALS- dnc-1 KD model

We employ a C. elegans model of ALS, dnc-1 KD model, in which the expression of dnc-1(homology with human dynactin-1) is knocked down (KD) specifically in motor neurons. Similar to the observation of ALS patients, the model shows progressive motor defects together with axonal and neuronal degeneration, along with other pathologies of SALS motor neurons.

Multi-Worm Tracker (MWT)

To develop candidate neuroprotective compounds, the MWT is applied to record the motor function of the dnc-1 KD animals using a high-resolution camera. The MWT system is automated, unbiased, highly efficient, and quantitative. The effectiveness of the adapted system was validated by detecting drug-induced motor defects in previous studies. On our platform, the modified system is adopted to record a larger field of view, which enables clients to effectively analyze a larger quantity of C. elegans at once.

Workflow of ASLS compounds screening

Workflow of ASLS compounds screening

With the advanced drug screening system and years of experienced technicians, Creative Biogene guarantees our clients the most reliable research services with comprehensive data analysis, faster turnaround time and most competitive prices. Please do not hesitate to contact us for more information. We are looking forward to cooperating with you!

Reference

  1. Ikenaka, K., et al. (2019). "A behavior-based drug screening system using a Caenorhabditis elegans model of motor neuron disease." Scientific reports, 9(1), 10104.

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