Huntington's Disease (HD) Drug Discovery Service
Creative Biolabs is a premier contract provider of neuroscience research products and services in the United States. You can count on us for all one-stop shop solutions for your Huntington's disease (HD) research, we promise to deliver. We challenge ourselves to think out of the box and innovate.
Overview of HD
HD is an autosomal dominant neurodegenerative disorder caused by a CAG trinucleotide repeat expansion in the HD gene. Clinical features of HD include cognitive, mental, and motor impairments, as well as peripheral phenotypes including weight loss and muscle atrophy. The striatum is the primary area of neuronal degeneration in HD. HD occurs worldwide in all races and ethnic groups with a prevalence of 5-10 cases per 100,000, but with an incidence as high as 1-3%.
Fig.1 Mechanisms of neurodegeneration induced by protein misfolding in HD. (Finkbeiner, 2011)
Drug Discovery and Development for HD
The understanding of proven targets is still in its infancy, so traditional target-based drug discovery strategies are of limited use. More recently, phenotypic assays were used to find molecules able to reverse some of the pathogenic mechanisms of HD. The pathogenic mechanism itself has been used to identify new, effective and HD-specific small molecules for drug discovery.
1) mHTT Aggregation/Lowering Assay
In Vitro Services for HD Research at Creative Biolabs
- Cell Culture Models
- Cell Viability and Cytotoxicity Assay
- Neuronal Plasticity Assay
- Neuroinflammation Assay
- Neurochemistry Assay
In Vivo Services for HD Research at Creative Biolabs
- Mouse Models for HD
The findings from animal model studies have helped elucidate important pathways that are disrupted in HD and have provided important insights into the pathogenesis of this disease. The different HD models represent a wide range of complementary tools for dissecting the pathogenesis of this disease.
1) Providing insights into normal huntingtin function
Wild-type huntingtin is necessary for development, as homozygous knockout mice show embryonic lethality. Wild-type huntingtin can be protective in different cell types and it can act against the toxicity caused by mutant huntingtin.
2) Revealing potential pathogenic mechanisms of the HD mutation
3) Powerful resource for testing therapeutic strategies
The availability of many different HD mouse models provides a powerful tool for preclinical testing of therapeutic strategies.
- Behavioral Testing Services
Tests of motor function in animal models of HD are commonly used to quantify disease progression. In rodents, a more extensive battery of tests has been used to characterize mHTT-related motor dysfunction, including spontaneous activity measures, the rotarod test, the climbing test, the balance beam test, and footprint gait analysis. General locomotor activity is measured by monitoring spontaneous or home cage activity using photobeam arrays or video tracking analysis packages.
- In Vivo Sampling
- Tissue Sampling
Therapies for HD
As the toxic and neurodegenerative pathogenesis of HD begins with an abnormal HTT gene and gene transcript (mHTT), it makes sense that disease-modifying therapy would directly target the mutant gene or immediate gene transcripts to lower the level of mutant HTT. Studies in mouse models have shown that suppression of mHTT or inactivation of the HTT gene can reverse HD-like behavioral and neuropathological phenotypes.
- Therapies Targeted at Aberrant Downstream Pathways
In HD, abnormal postsynaptic activation of pro-death pathway signaling is present at the corticostriatal synapse. Several post-synaptic proteins are involved in this abnormal downstream signaling, including the extrasynaptic NMDA receptor (GluN2B), sigma 1 receptor (SIG1R), postsynaptic density protein 95 (PSD95), and phosphodiesterase 10A (PDE10A).
Creative Biolabs' experienced R&D team provides you with all the support you need during drug development for HD research that is in the pipeline, both including products and services. Our solutions range from study design consultancy to data generation and data interpretation. Contact us to discuss your next HD project.
Reference
- Finkbeiner, S. Huntington's disease. Cold Spring Harbor perspectives in biology. 2011, 3(6): a007476.
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