Phenotypes typically become evident from 10 weeks of age, making this a reliable time point for assessing therapeutic interventions (Zhang et al., 2021). We recommend getting in touch with our scientific team to discuss the specifics of your study, including the most appropriate age to start, dosing schedules, and recommended readouts, as these may depend on your therapeutic treatment strategy as well as your therapeutic target’s mechanism of action (MoA), among others. Contact us now. 

Yes, the Kabuki Syndrome phenotype in this model has been shown to respond to postnatal treatment with agents that favor chromatin opening, such as HDAC inhibitors or the endogenous HDAC inhibitor-like ketone body β-hydroxybutyrate, highlighting its value for early-stage epigenetic drug development (Bjornsson et al., 2014). 

Lysine-specific histone demethylase 1A (LSD1) removes H3K4 methyl marks introduced by KMT2D (Shi et al., 2004) and has therefore been hypothesized to mitigate the molecular and phenotypic impairments resulting from KMT2D loss of function (Cao et al., 2018). Previous research has demonstrated that treatment with an LSD1 inhibitor rescued defects in adult neurogenesis, restored proper gene expression, and rectified the genome-wide deficiency of specific histone methylation (Zhang et al., 2021).  

Treatment with an LSD1 inhibitor led to normalization of memory and visuospatial learning deficits in Kmt2d+/βGeo mice, demonstrating the model’s utility in evaluating epigenetic therapies (Zhang et al., 2021). 

Currently, vafidemstat, a clinical-stage LSD1 inhibitor developed by Oryzon Genomics, a biopharmaceutical company focused on the development of epigenetic-based drugs for CNS diseases and oncology, is being tested in the Kmt2d mouse model by InnoSer under a collaboration established between Kabuki Syndrome Foundation and Oryzon Genomics.