Huntington's Disease (HD) Humanized Model Development Service

Are you currently facing challenges in preclinical drug development for complex neurological disorders like Huntington's disease (HD), specifically in achieving high translational fidelity and validating allele-specific therapies? Our HD humanized models help you accelerate drug discovery and obtain highly predictive preclinical data through advanced genetic engineering and comprehensive phenotypic characterization.

HD is a devastating inherited neurodegenerative disorder caused by a CAG repeat expansion in the HTT gene, leading to a toxic mutant huntingtin protein. This protein drives progressive motor, cognitive, and psychiatric symptoms. Humanized mouse models are indispensable tools for HD research, providing a bridge between in vitro studies and clinical trials. These models incorporate human genetic material or disease-relevant genetic modifications into the mouse genome, offering enhanced translational fidelity compared to traditional animal models, as evidenced by their utility in evaluating allele-specific therapies and splicing modulators.

How Our Huntington's Disease Humanized Models Can Assist Your Project

Creative Biolabs' HD humanized models provide robust platforms for evaluating the efficacy, pharmacokinetics, and safety of your therapeutic candidates in a highly relevant biological context. Our models are specifically engineered to recapitulate key aspects of human HD pathophysiology, from genetic mutations to complex behavioral and neuropathological phenotypes. This allows for precise target validation and streamlined screening of novel compounds, including small molecules, biologics, and gene therapies. We deliver actionable insights that bridge the gap between preclinical research and clinical trials, enabling more confident progression to clinical development.

Discover How We Can Help - Request a Consultation

Workflow:

• Required Starting Materials: To initiate a project with CBL, clients typically need to provide:

1. Compound Specifications: Detailed information on the therapeutic agent, including its chemical structure, proposed formulation, dosage range, and preferred route of administration.
2. Research Objectives and Endpoints: Clearly defined scientific goals for the study, specifying desired outcomes such as improvements in motor function, cognitive performance, specific biochemical markers (e.g., mHTT levels), or neuropathological changes.
3. Existing Preclinical Data: Any available in vitro or preliminary in vivo data that supports the compound's mechanism of action or provides insights into its initial efficacy and safety profile.

• Final Deliverables: Upon completion of the service, clients receive:

1. Detailed Study Report: A comprehensive document encompassing the full experimental design, detailed methodologies, raw and analyzed data, statistical results, and scientific interpretation of findings.
2. Publication-Ready Data: High-resolution figures, graphs, and tables summarizing key results, suitable for presentations or scientific publications.
3. Expert Scientific Consultation: Opportunities for in-depth discussions with our lead scientists to review the study outcomes, discuss implications, and strategize next steps for your research program.

The typical timeframe for a preclinical efficacy study using our humanized HD mouse models ranges from 12 to 24 weeks, depending on factors such as the complexity of the study design, the duration of compound administration, and the breadth of phenotypic endpoints selected.

Why Choose Us?

CBL offers unparalleled expertise and innovation in HD humanized mouse models, making us the premier partner for your preclinical research. Our twenty years of specialized experience translate into rigorously validated models and precise, actionable data. We are at the forefront of genetic engineering, consistently integrating new technologies to create models that faithfully replicate human disease, ensuring superior translational predictability.

Experience the CBL Advantage - Get a Quote Today

Huntington's Disease Humanized Models

Our comprehensive suite of models encompasses various approaches to best suit diverse research needs:

• Fragment Models (e.g., R6/2, N-171): These transgenic models express a truncated N-terminal portion of the human mutant HTT protein. They exhibit a rapid, aggressive disease phenotype with early onset of motor and cognitive deficits, along with prominent neuronal intranuclear inclusions. While not fully recapitulating the slow progression of human HD, their accelerated pathology makes them ideal for rapid screening of compounds and investigating early pathogenic events. For instance, the R6/2 model (carrying 120-160 CAG repeats) shows early choreiform-like movements and premature death, allowing for quick assessment of therapeutic impact on overt symptoms.
• Full-Length Human HTT Transgenic Models (e.g., YAC, BACHD, Hu128/21): These models integrate the full-length human HTT gene with expanded CAG repeats into the mouse genome. They develop a more progressive, slower-onset phenotype that more closely mirrors the chronic nature of human HD. The YAC128 model, containing a yeast artificial chromosome with a 128 CAG repeat expansion, displays progressive motor impairment and neurodegeneration. The BACHD model, expressing full-length human human HTT with 97 CAG repeats, also exhibits progressive motor and cognitive deficits. Crucially, the recently developed Hu128/21 model stands out. Like YAC128, it derives mutant huntingtin from the YAC128 transgene and maintains similar levels of both wild-type and mutant huntingtin. Its 100% homology to human HTT makes it exceptionally valuable for evaluating therapeutic approaches, such as allele-specific antisense oligonucleotides (ASOs), which require precise targeting of human-specific sequences, as shown in recent preclinical studies. Furthermore, models with human introns are essential for studying the on-target effects of splicing modulators, as human splicing mechanisms can differ from those in mice.

What We Can Offer

At CBL, our HD Humanized Mouse Models service is designed to provide you with comprehensive, high-quality solutions tailored to your specific research needs. We are committed to accelerating your path to therapeutic discovery and development.

• Diverse Model Portfolio: Access to a broad range of rigorously validated humanized HD mouse models, including fragment, full-length, knock-in, and fully humanized lines, allowing for optimal model selection based on your research objectives.
• Customized Model Generation: Expertise in advanced genetic engineering techniques to develop bespoke HD mouse models with specific genetic modifications, ensuring the highest relevance for your unique therapeutic targets.
• Comprehensive Phenotypic Characterization: State-of-the-art capabilities for detailed behavioral, neuropathological, and biochemical assessments, providing a holistic understanding of disease progression and therapeutic efficacy.
• Allele-Specific Therapy Validation: Specialized platforms, such as our Hu128/21 model, for precise evaluation of allele-specific therapeutic strategies, crucial for developing highly targeted and safe treatments.
• Optimized Study Design and Execution: Collaborative development of tailored experimental protocols, ensuring scientific rigor, efficient resource utilization, and timely delivery of results.
• Expert Scientific Consultation: Direct access to our team of seasoned biology experts with over 20 years of experience in neurodegenerative disease research, offering invaluable guidance and interpretation throughout your project.
• Robust Quality Control: Adherence to stringent quality assurance protocols at every stage, from model breeding and maintenance to data collection and analysis, guaranteeing the reliability and reproducibility of your findings.

Related Services

To further support your comprehensive drug discovery and development efforts for neurodegenerative diseases, CBL offers several complementary services:

• Neurodegenerative Disease Biomarker Discovery: Leverage our expertise in identifying and validating novel biomarkers specific to HD progression and therapeutic response.
• AAV Vector Development and Production: High-quality adeno-associated virus (AAV) vector design and production for gene therapy applications, ensuring optimal gene delivery to the central nervous system.
• Custom Genetic Engineering Services: For unique research needs, our advanced genetic engineering capabilities allow for the creation of bespoke rodent models with specific genetic modifications.
• Behavioral Phenotyping Core: Access our state-of-the-art behavioral phenotyping facilities for comprehensive assessment of motor, cognitive, and psychiatric function in your preclinical models.

Creative Biolabs is your dedicated partner in the fight against Huntington's Disease. Our advanced humanized mouse models, coupled with our deep scientific expertise and commitment to precision, provide the foundational insights necessary to accelerate your therapeutic development. We are uniquely positioned to help you translate promising research into effective treatments, ultimately bringing hope to patients and families affected by HD.

Contact Our Team for More Information and to Discuss Your Project