Abstract
Huntington’s disease ( is an autosomal dominant neurodegenerative condition caused by repeat expansions of CAG trinucleotides in the huntingtin gene. The development of animal models for HD in a range of species has provided insights into its pathogenesis and allowed the generation of potential therapies. However, these showed limited or no efficacy when tested in clinical trials. Thus, there is an unmet need for physiologically relevant human cellular platforms for in vitro drug screening
At Axol Bioscience Ltd, we utilise our expertise on reprogramming, CRISPR/Cas 9 genome editing, and disease relevant cell differentiations to generate hiPSCs derived in vitro models. We have reprogrammed 150 patient derived iPSC lines, from which 46 are derived from HD donors spanning 39 to 127 CAG trinucleotide repeats using the Sendai virus based CytoTune 2 0 kit. The hiPSC lines have been qualified based on a range of tests, including microbiology, growth profile, cell line identity, vector clearance, karyology, pluripotency assessment and differentiation potential to ensure they are of the highest standards We have also successfully differentiated 2 independent clones of HTT 120 CAG to microglial cells, cortical neurons and astrocytes highlighting the potential of these lines to become HD relevant cell types. This, together with the development of isogenic controls, constitutes a powerful platform for high content screenings and developing gene therapy.
