At Axol Bioscience, we’re utilizing over a decade of experience to help researchers looking to harness iPSC technology to build better human disease models. In this short article, we describe our work enhancing in vitro Huntington’s Disease models, including our recent activity at the CHDI Annual Huntington’s Disease Therapeutics Conference.
Human iPSCs could transform Huntington’s Disease drug discovery
Huntington’s disease (HD) is an autosomal dominant neurodegenerative condition caused by repeat expansions of CAG trinucleotides in the Huntingtin gene (HTT). The mutated HTT protein drives the death of striatal neurons in the basal ganglia, causing a range of progressive motor, cognitive and psychiatric symptoms that are ultimately fatal [1].
Although HD animal models have provided some insights into its pathogenesis, they are understood to have a limited ability to recapitulate human physiology[1][2]. To close this translational gap, researchers have been turning to human induced pluripotent stem cells (iPSCs) as the fuel for human-relevant testing platforms.
By taking cells from real people (for example, from blood samples) and reprogramming them into iPSCs, researchers can then generate disease-relevant endpoint cells to build human-relevant in vitro models. And because these cells retain their donor characteristics, you can incorporate HD patient-derived cells to better understand the disease, or test potential therapeutics, on cells that express the HTT mutation.
If you’d like to learn more about our Huntington’s Disease iPSC axoLinesTM, click here: Huntington’s Disease | Axol Bioscience
Supporting the Huntington’s Disease research community
As part of our ongoing commitment to collaboration, we recently attended the 19th Annual Huntington’s Disease Therapeutics Conference to discuss the value of iPSC technology for advanced in vitro Huntington’s Disease models.
At this CHDI conference, we presented two posters on our work building more human-relevant in vitro Huntington’s Disease models using iPSCs. These posters served as excellent discussion points for HD researchers in attendance, demonstrating the utility and relevance of our iPSC-based Huntington’s Disease models, as well as our axoServicesTM assay capabilities for researchers who want us to do the “heavy lifting” so they can focus on the science.
Poster 1: Characterization of striatal neurons derived from >140 CAG iPSCs for Huntington’s Disease modeling
Consistent, functional striatal neurons are the key to building useful in vitro HD models. In collaboration with Harness Therapeutics, we demonstrated the characterization of a patient-derived iPSC line (and differentiated axoCells striatal neurons) for use in in vitro HD models.
In this poster, we describe:
- Our work building a human iPSC-derived striatal neuron HD model utilizing a patient line with >120 CAG repeats
- The extensive characterization of this patient line, including genetic analysis (highlighting the somatic instability of the CAG repeats sequence), key marker expression and morphology
- Data on the functional characterization of this HD line comprising neurite outgrowth and electrophysiology assays
- Our outlook for future work, including further characterization and co-culture models
Click here to download the poster “Characterization of striatal neurons derived from >140 CAG iPSCs for Huntington’s Disease modeling”: Characterization of iPSC-derived striatal neurons for HD modeling (axolbio.com)
Poster 2: Creation of RUES2 Cell Lines Carrying Targeted Modifications at the HTT Gene
In collaboration with CHDI, we used CRISPR-Cas9 technology to generate stem cell lines with targeted HTT gene modifications for a powerful model to understand HD biology.
Key highlights of the poster are:
- The use of gene editing technology to produce stem cell lines carrying different CAG repeat lengths
- Data on the characterization of these cell lines including morphology, flow cytometry, karyology and Sanger sequencing
- Our outlook on using these lines to produce complex co-culture models comprising striatal neurons, astrocytes and cortical excitatory neurons
Click here to download the poster “Creation of RUES2 Cell Lines Carrying Targeted Modifications at the HTT Gene”: Poster: Creating RUES2 cell lines: targeted HTT gene modifications (axolbio.com)
