Kleefstra Syndrome
Kleefstra syndrome results from a mutation or deletion in the EHMT1 gene and falls under the category of rare genetic disorders. Protheragen claims to have a skilled group of researchers and scientists with deep knowledge pertaining to Kleefstra syndrome. They are determined to be at the forefront of developing novel therapies for Kleefstra syndrome, seeking to fill gaps in therapeutic options and push forward the field of precision medicine.
Introduction to Kleefstra Syndrome
Kleefstra syndrome, which was referred to as 9q34.3 deletion syndrome in the past, is one of the rarest neurodevelopmental disorders resulting due to haploinsufficiency of the EHMT1 gene. The syndrome features include autism spectrum disorder (ASD)-like behaviors, intellectual disability, significantly impaired communication, weakened muscle tone, epilepsy, distinct sleep disorders, and unique craniofacial changes.
Fig.1 Clinical features of Kleefstra syndrome. (Lee T N, et al., 2023)
Pathogenesis of Kleefstra Syndrome
Due to deletions at 9q34.3 or inactivating mutations, Kleefstra syndrome is best characterized by haploinsufficiency of the EHMT1 gene. EHMT1 is responsible for encoding a histone methyltransferase that does a critical epigenetic mark of dimethylating histone H3 at lysine 9 (H3K9me2) on histones on genes. EHMT1 loss of function leads to rampant transcriptional dysregulation across the board especially in genes associated with neurons which hinders synaptic plasticity, GABAergic signaling, and cortical development.
Fig.2 Maintenance of DNA methylation: Glp and G9a are known to target H3K9 for mono and di-methylation. (Adam M A, Isles A R., 2017)
Therapeutic Development for Kleefstra Syndrome
| Drug Names | Mechanism of Action | Targets | Research Phase |
| Olanzapine | Olanzapine is an atypical antipsychotic that works by antagonizing dopamine D2 receptors and serotonin 5-HT2A receptors in the brain, helping to balance neurotransmitters. | Dopamine D2 receptors, serotonin 5-HT2A receptors | Approved |
| Aripiprazole | Aripiprazole is a partial agonist at dopamine D2 and serotonin 5-HT1A receptors, and antagonist at serotonin 5-HT2A receptors, stabilizing mood and behavior. | Dopamine D2 receptors, serotonin 5-HT1A and 5-HT2A receptors | Approved |
| Levetiracetam | Levetiracetam is an anticonvulsant that modulates synaptic neurotransmitter release by binding to the synaptic vesicle protein SV2A, reducing neuronal excitability. | Synaptic vesicle protein SV2A | 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
Protheragen specializes in providing cutting-edge diagnostic and therapeutic development services for rare neurodevelopmental disorders, including Kleefstra syndrome. We focus on creating advanced disease models to better understand Kleefstra syndrome pathogenesis, and we utilize innovative blood-brain barrier (BBB) models to enhance the delivery and efficacy of therapeutic compounds.
Therapeutic Development Services
By Mechanism of Action
Disease Model Development Services
In Vitro Model Development
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Ehmt1+/- Mice: These mice exhibit core symptoms of Kleefstra syndrome, including intellectual disability, craniofacial malformations, and autism-like behaviors, and are valuable for studying the underlying mechanisms and treatments for the disorder.
Focusing on preclinical research, Protheragen offers comprehensive pharmacodynamic (PD), pharmacokinetic (PK), and toxicology study services to support the development and regulatory approval of potential therapies. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
References
- Lee T N, Rechetello H E L, Lima J B D A, et al. Multiple copy number variation in a patient with Kleefstra syndrome[J]. Revista Paulista de Pediatria, 2023, 42: e2022230.
- Adam M A, Isles A R. EHMT1/GLP; biochemical function and association with brain disorders[J]. Epigenomes, 2017, 1(3): 15.