Drug Screening Service for Huntington's Disease
Huntington's disease (HD), also known as Huntington's chorea, is an autosomal dominant, inherited neurodegenerative disorder characterized by progressive motor deficits, dementia, emotional disturbance and even neuronal death. The disease is caused by the expansion of a polyglutamine (polyQ) tract in the human huntingtin protein (Htt). However, the molecular mechanisms of Htt proteotoxicity are still unknown, and the muscle phenotypes have not been well studied. Here, we provide the therapeutic compound identification service for HD using C. elegans, hoping to quickly identify interventions for HD and decode the underlying mechanism of drug action.
Caenorhabditis elegans as a model organism for PD studies
Huntington's Disease (HD) was first described by George Huntington in 1872, characterized by dance-like spasmodic movements and typically manifest at around 40 years of age. At present, it is widely known that HD is an autosomal dominant, inherited neurodegenerative disease with distinct phenotypes, including impaired motor coordination associated with chorea and progressive deterioration of cognitive function. It occurs due to a mutation in the huntingtin gene with an abnormal CAG repeat, leading to a variable length N-terminal polyglutamine chain (poly-Q). The polyglutamine expansion destabilizes Htt leading to protein folding and aggregates formation, thereby triggering neurodegeneration (closely connected with age and polyQ tract length) and the disruption of energy metabolism in muscle cells. The investigation of potential HD therapeutic compounds takes more time and cost in mammalian models due to the prolonged time course of this disease. Therefore, a rapid and inexpensive alternative is urgently needed to assess the efficacy of numerous candidate compounds, such as the invertebrate models. As an invertebrate organism, C. elegans has provided an attractive model system due to its unique experimental advantages, its easy genetic manipulation, and high homology of genes and signaling pathways with mammals. Consequently, the nematode is an optimal alternative for screening potential compounds in the early stages of drug development for age-related diseases.
Service offerings
Generation of C. elegans HD models
The C. elegans HD model generation service includes plasmid constructs and transgenic animal generation, such as Htt-Q150 and Htt513. In addition, to evaluate the success of model construction, a series of assays are employed, including fluorescence microscopy, motility assays, lifespan assays, Western blot, and mRNA analysis.
Identification of potential therapeutic compounds for HD
- Compound concentration range for screening in C. elegans
We offer the C. elegans HD model to perform the food clearance assay, a systematic method for selecting optimal compound concentrations. The variation of C. elegans growth, survival or fecundity is positively correlated with the rate of E. coli suspension (food source) consumption. The assay is based on the short lifespan and capability of C. elegans growing in liquid culture of E. coli.
Schematic diagram of HD compounds screening strategy
We optimize assays for the rapid assessment of potential compounds' efficacy using C. elegans HD models.
CD BioSciences is a professional provider of C. elegans model services. We offer a systematic platform that enables rapidly and inexpensively screen potential HD drugs and elucidate pathways of drug action. If you have any projects requiring our service, don't hesitate to contact us. We guarantee our clients the most reliable research services to best match your research goals with more comprehensive data analysis and faster turnaround time.
Reference
- Voisine C., et.al. (2007). "Identification of potential therapeutic drugs for huntington's disease using Caenorhabditis elegans". PLoS One. 2(6): e504.
* For research use only.
