Kabuki Syndrome
Because of the multitude of symptoms and severe health complications Kabuki syndrome has, it requires a multidisciplinary approach to manage it. Protheragen strives through advanced therapeutic development and disease modeling services to improve the treatment and understanding of Kabuki syndrome. We aim to offer comprehensive solutions spanning from therapeutic research of Kabuki syndrome through to its commercialization.
Introduction to Kabuki Syndrome
Kabuki syndrome was first identified in 1981 and it is marked by unique facial characteristics, an intellectual disability, and involvement of multiple organ systems. There is an estimated occurrence rate of 1 in 32,000 births which is caused by prominent mutations in two epigenetic regulators KMT2D and KDM6A.
Fig.1 Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome. (Zhang L, et al., 2021)
Pathogenesis of Kabuki Syndrome
Kabuki syndrome is primarily caused by heterozygous loss-of-function mutations in KMT2D (a histone methyltransferase) or KDM6A (a histone demethylase), which disrupt the balance of H3K4 methylation and H3K27 demethylation. This epigenetic dysregulation leads to widespread alterations in gene expression during development, particularly affecting WNT, NOTCH, and IGF-1 signaling pathways, resulting in the characteristic neurodevelopmental, craniofacial, and multisystem manifestations of the disorder.
Therapeutic Development for Kabuki Syndrome
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Somatropin | Somatropin is a synthetic growth hormone that stimulates growth, cell reproduction, and cell regeneration in humans. It mimics the effects of natural growth hormone. | Growth hormone receptors | Approved |
| Valproic Acid | Valproic acid is an anticonvulsant and mood-stabilizing drug that works by increasing the availability of gamma-aminobutyric acid (GABA), a neurotransmitter in the brain. It also has effects on ion channels and histone deacetylase inhibition. | GABA receptors, ion channels, histone deacetylases | Approved |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
To advance the effective management of Kabuki syndrome, Protheragen offers comprehensive diagnostic and therapeutic development services. With a focus on the diverse molecular mechanisms driving Kabuki syndrome, we are dedicated to developing innovative and targeted therapies that address the significant unmet medical needs. Our team excels in creating highly accurate disease models, enabling rigorous evaluation of the safety, efficacy, and mechanism of action of potential therapeutics.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
- Kmt2d Mutant Mouse Model: This model, constructed by heterozygous knockout of the Kmt2d gene through genetic engineering technology, is used to simulate human KMT2D haploinsufficiency and reproduce the key features of Kabuki syndrome.
- Other Models
At Protheragen, we are dedicated to supporting the development of innovative therapies through comprehensive preclinical research services. Our expertise spans pharmacodynamics (PD), pharmacokinetic (PK) and toxicology studies, ensuring a thorough evaluation of your therapeutic candidates. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Zhang L, Pilarowski G, Pich E M, et al. Inhibition of KDM1A activity restores adult neurogenesis and improves hippocampal memory in a mouse model of Kabuki syndrome[J]. Molecular Therapy Methods & Clinical Development, 2021, 20: 779-791.