Huntington’s Disease
iPSC models for Huntington's Disease drug discovery
Huntington’s Disease (HD) is an autosomal dominant neurodegenerative disorder which has no cure. It is characterized by a profound loss of striatal neurons in the basal ganglia which drives a range of progressive motor, cognitive and psychiatric symptoms. Advanced in vitro HD models are a key tool for research and drug discovery, and central to these models is the production of functional striatal neurons.
Expansion of CAG repeats in the Huntingtin gene (HTT) produces a mutant version of the huntingtin protein whose presence becomes toxic to brain cells, leading to cell death and underlying the progressive pathology of Huntington’s Disease.
At Axol Bioscience, we have reprogrammed a human induced pluripotent stem cell (iPSC) line from an HD patient with > 120 CAG repeats. After reprogramming and generation of the master bank, the number of CAG repeats was 144 and CAG expansion analysis during 15 passages showed an increase of 1 CAG repeat every 5 passages. Further study suggested that this line has an atypical allele associated with hastening the onset and progression of the disease.
iPSC-derived striatal neurons for HD research
Axol has a well established process for manufacturing striatal neurons for Huntington’s Disease research. Derived from consenting donor cord blood and fibroblasts, our striatal neurons have been specifically developed for use in mono-, co- and tri-culture models of neurodegenerative disease and for drug discovery.
The majority of human striatal neurons are γ-amino butyric acid (GABAergic) projection medium spiny neurons (MSNs). These cells typically express dopamine and cAMP-regulated phosphoprotein (DARPP32). It is these cells that specifically degenerate in the early phase of Huntington’s disease (HD), causing progressive loss of the patient’s motor and cognitive functions.
Striatal neurons are provided as frozen neuronal stem cells along with specialist media and supplements and a protocol to drive maturation to the final assay ready endpoint. Axol can provide striatal neurons from unaffected (‘control’) donor lines and from a range of donors who had expanded CAG repeats.
Learn more about striatal neurons here.
Long-range Ht instability studies + CAG repeat sequencing
Axol has completed a series of client service projects to maintain long-range (100 day) iPSC-derived striatal neuron cultures for the purpose of genomic instability studies. We can additionally utilise FAN1. We have also developed a robust and meaningful CAG repeat sequencing methodology for both mid point and endpoint asssessment.
See us at the CHDI conference!
Axol will be attending and presenting new posters at the 2025 CHDI conference.
| Donor Condition | Lines Available |
| Huntington’s Disease | Female, 40-50, HTT: 18/39 CAG |
| Female, 51, HTT: 42/17 CAG | |
| Female, 7, HTT: 125/14 CAG | |
| Male, 16, HTT: 28/66 CAG | |
| Male, 64, HTT: 17/38 CAG (Asymptomatic Carrier) |
