Huntington's Disease Models Service

Introduction to Huntington's Disease Models

Overview of Huntington's Disease

Fig.1 Progression of Huntington's disease over a patient's lifespan.¹

Huntington's disease (HD), an incurable hereditary progressive neurodegenerative disorder accompanied by symptoms, such as dementia, chorea, and depression, is caused by the loss of the GABAergic medium spiny neurons (MSNs) in the striatum. Degeneration of GABAergic MSNs causes an empty space in the brain, which is greatly increased in the HD patient brain. For individuals affected with HD, there is an expansion of the CAG repeat region within the huntingtin (HTT)-encoding genes, resulting in aggregates of polyglutamine. The clinical course of HD is progressive for many years, ultimately leading to severe brain atrophy and death. The disease is inherited in an autosomal dominant manner, and it occurs at a rate of 4-10 individuals per 100,000 population, mostly in 30-40-year-olds. However, therapeutic agents for the treatment of HD have not yet been developed.

Importance of In Vitro Models in HD

To study HD pathology, researchers have relied on animal models. Animal models have revealed many fundamental findings, however, animal models suffer from various drawbacks: (1) The use of animals for research has raised ethical concerns from animal rights groups; (2) There is a wide gap between animal and human physiology, so one must always extrapolate animal data to predict the human scenario. Animal models, for the aforementioned reasons, are increasingly falling out of favor. Therefore, researchers have developed more suitable in vitro systems to elucidate HD pathophysiology.

Services at Creative Biolabs

Devoted to in vitro CNS diseases modeling services for more than 10 years, Creative Biolabs has gradually optimized our platform with advanced equipment, emerging technology, and professional talent. We are now capable of offering a variety of in vitro CNS disease models and open the platform to customers around the world. Huntington's disease models service is one of the models we are good at.

If you are interested in ex vivo Huntington's disease models, or any other custom CNS diseases modeling services on the websites, please feel free to contact us for more information.

Our service involves:

• Cell Line Generation: The cell models generated can include patient-derived cells, genetically engineered cells, and iPSCs. By manipulating the HD mutation in these cell lines, we can create different disease severity models.
• Cellular Characterization: Post-generation of cell lines, we undertake a detailed evaluation of cellular properties including genotype-phenotype correlation, gene expression levels, apoptosis, cell viability, and functionality assays.
• Development of Neurodegenerative Models: Our scientists can develop neuronal and glial cells from HD patient-derived or genetically engineered cell lines. These models allow for a thorough evaluation of the disease mechanism, including misfolded proteins, mitochondrial dysfunction, and oxidative stress associated with HD.
• CRISPR/Cas9 Genome Editing: We utilize CRISPR/Cas9 genome editing techniques for precise modification of genes associated with HD.
• Proteomic and Genomic Analysis: Our service also includes proteomic and genomic analysis to identify HD hallmark proteins and genes, and study their role in disease progression.

By rendering this service and related services, we aim to accelerate research and drug discovery in neurodegenerative diseases, including but not limited to:

Published Data

Kim Le Cann, et al. compared two previously published protocols to obtain hiPS cell-derived striatal neurons from healthy donors and patients with Huntington's disease. Patch-clamp experiments, immunostaining, and RT-qPCR were performed to characterize neurons in culture. Although the neurons were mature enough to elicit action potentials, most neurons failed to express typical markers of the medium spiny neurons (MSN).

They used hiPS cell lines from non-HD donors as well as from patients with different juvenile-onset HD. The results of the immunostaining studies highlight that both protocols appear to generate only a few striatal MSNs. This demonstrated the current challenges in reproducing previously published data on differentiation protocols and generating hiPS cell-derived striatal MSN to mimic inherited neurodegenerative diseases in vitro.

Fig. 2 Immunostaining of hiPS cell-derived neurons of both differentiation protocols.²

Application of In Vitro Models in HD Research

Until now, many stem cell-based 2D in vitro HD models have been developed, but a limited number of relevant physiological models exist. For example, Zhang et al. used suspensions of self-aggregating HD-iPS cells to generate NSCs. Within this 3D system, the HD-NSCs differentiated into striatal neurons containing the same CAG expansion found in the HD patient from whom the iPS cell line was established. Such differentiated cells could serve as a human HD cell model to analyze its pathophysiology or for drug screening.

FAQs

Q: What types of assays can you perform using these Huntington's disease models?

A: We can conduct a variety of assays, including but not limited to, neurotoxicity assays, gene expression profiling, protein aggregation studies, and electrophysiological measurements. Additionally, we can perform high-throughput drug screening and evaluate cellular responses to therapeutic interventions, providing comprehensive data on potential treatments.

Q: Are there any ethical considerations or regulatory approvals required for using these models?

A: Since our models are derived from cell lines and not from animal or human subjects, they typically do not require the same level of ethical and regulatory approvals. However, if the models are derived from human iPSCs, appropriate consent and ethical approvals are obtained during the cell derivation process. We comply with all relevant guidelines and regulations to ensure ethical standards are met.

Q: Have the developed models been used in published research?

A: Yes, the models we have developed are often used in high-impact academic and pharmaceutical research and have been cited in numerous scientific publications. These show the reliability and validity of our models.

Q: What are the costs associated with developing and maintaining a Huntington's disease model?

A: The costs can vary based on the complexity of the model and the specific services required. We offer a range of options, from basic models to fully customized solutions. Maintenance costs depend on the type of culture and frequency of required assays. We provide detailed quotes after discussing your specific needs to ensure transparency and budget alignment.

Scientific Resources

Neuroimaging as a Tool for Modeling CNS Diseases

References

1. Ross, C. A. and Tabrizi, S. J. Huntington's disease: from molecular pathogenesis to clinical treatment. Lancet Neurol. 2011, 10(1): 83-98.
2. Le Cann, Kim, et al. "The difficulty to model Huntington's disease in vitro using striatal medium spiny neurons differentiated from human induced pluripotent stem cells." Scientific reports 11.1 (2021): 6934.

For Research Use Only. Not For Clinical Use.