Developing next-generation in vitro phenotypic assays for Huntington’s disease by combining a precision reprogrammed hiPSC-derived disease model with high-density microelectrode arrays

Huntington’s disease (HD) is a fatal neurodegenerative disorder caused by the expansion of the CAG trinucleotide repeat in the huntingtin (HTT) gene leading to the expression of a mutant protein (mHTT), which affects neuronal health and function. There is currently no effective cure or treatment to slow down or stop the disease’s progression. One reason for this is the lack of accurate and easy-to use HD models that recapitulate the phenotypes and pathology seen in patients. Additionally, more advanced methods are required to record and analyze functional properties of cultured neurons over the entire maturation period, in order to gain insights into the underlying mechanisms of neurodegenerative diseases.

In this app note you will learn:

• How Charles River Laboratories utilised the MaxTwo high-density microelectrode array from MaxWell Biosystems to functionally characterise the ioGluamatergic Neurons HTT50CAG/WT Huntington's disease model from bit.bio.
• How ioGlutamatergic Neurons HTT50CAG/WT and ioGlutamatergic Neurons form a genetically matched isogenic system that allows scientists to attribute experimental outcomes directly to the 50 CAG repeat expansion known to cause Huntington's disease.
• How using the MaxTwo system, Charles River generated phenotypic data showing bit.bio's Huntington's disease model has delayed neuronal network formation, decreased axonal branching and decreased spontaneous activity compared to the isogenic control.