Huntington’s Disease Studies
Huntington's disease (HD) is an autosomal neurodegenerative disorder characterized by motor, behavioral, cognitive and metabolic dysfunction caused by the expansion of a CAG trinucleotide repeat region in the huntingtin gene (HTT). Recently, a new antisense oligo therapy was reported to show efficacy in reducing levels of mutant huntingtin protein in early-stage patients.
We have created a schematic showing our end-to-end drug discovery capabilities for Huntington’s disease. View Schematic
Charles River has a long-standing track record of partnership with CHDI to develop new targets and assays as well as provide lead compound efficacy screening services. We offer studies for in vitro assays to quantify huntingtin (HTT) protein as well as fully customizable studies using two comprehensively validated mouse models.
Our team has developed an assay to detect mouse and human forms of wild type and mutant Huntingtin protein using an MSD assay platform and this work has been published recently.
In addition to the in vitro assays, Charles River has validated the following mouse models of Huntington’s disease:
- The transgenic R6/2 mouse model that contains about 120 CAG repeats to mimic the trinucleotide repeats seen in Huntington’s disease.
- The Q175 knock-in mouse model where exon1 of the mouse huntingtin gene is replaced with exon 1 of the human huntingtin gene that includes about 190 CAG repeats.
The mouse models have been validated using various biochemical markers, behavioral endpoints, gait changes and cognitive testing. Some of the tools that have been used to validate the Huntington’s disease mouse model include magnetic resonance imaging (MRI), magnetic resonance spectroscopy (MRS), cognitive testing using touchscreen methods, movement changes using fine motor kinematic analysis and electrophysiology assays. In addition, biochemical methods such as histology, immunohistochemistry and qPCR are included to detect biochemical endpoints.