CDKL5 Deficiency Disorder (CDD)
CDKL5 deficiency disorder (CDD) is a rare developmental epileptic encephalopathy caused by mutations in the CDKL5 gene. It is one of the most common forms of inherited epilepsy. With our deep expertise in CDD research, we offer tailored solutions and support throughout the entire journey from CDD therapy development to successful commercialization.
Overview of CDKL5 Deficiency Disorder (CDD)
Studies have shown that CDKL5 Deficiency Disorder (CDD) occurs in approximately 1:40,000 to 1:60,000 live births. The disease-causing gene CDKL5, which stands for cyclin-dependent kinase-like 5, is located on the X chromosome. This gene provides instructions for making proteins that are essential for normal brain and neuron development. The CDKL5 protein acts as a kinase, an enzyme that regulates the activity of other proteins by adding oxygen and phosphate atoms at specific positions.
Research has shown that mutations in the CDKL5 gene result in the malfunctioning of the CDKL5 protein, which in turn disrupts normal brain development and function. The exact mechanisms by which CDKL5 mutations lead to the clinical symptoms of CDD are still not fully understood. However, studies have suggested that the CDKL5 protein may target specific proteins involved in neuronal signaling, synaptic plasticity, and gene expression.
Fig.1 Known CDKL5 targets and affected processes in neurons. (Maranga, Carina, et al., 2020)Diagnostics Development of CDD
Various genetic tests can be used to diagnose CDD which include sequencing the CDKL5 gene, testing for small deletions or duplications within the gene, screening with a panel of known epilepsy genes, using an intellectual disability gene panel, or performing a chromosomal microarray to check for larger deletions involving the CDKL5 gene. Another option is whole exome sequencing. In some cases, the testing may reveal variants in the CDKL5 gene that have not been previously associated with the disorder, known as "variants of uncertain significance." Further investigation, such as testing both parents for the variant, may be required in such cases
Therapeutics Development of CDD
- Drugs for CDD
Ganaxolone, a neurosteroid that acts as an allosteric modulator of GABA-A receptors, has shown a significant reduction in major motor seizure frequency compared to placebo in a phase III clinical trial.
Soticlestat, a selective cholesterol 24-hydroxylase (CH24H) inhibitor. This drug modulates the NMDA receptor and has shown a reduction in major motor seizures in individuals with CDD.
- Types of CDD Therapy Development
Pharmacological Interventions
The use of antiseizure medications (ASMs) remains a common approach to managing seizures in individuals with CDD. Medications such as clobazam, topiramate, steroids, valproic acid, and lamotrigine have shown some efficacy in reducing seizure frequency in CDD.
Cannabis Derivatives
The potential therapeutic benefits of cannabis derivatives, particularly cannabidiol (CBD), have also been investigated in individuals with CDD. A study reported a reduction in motor seizures with the use of Epidiolex, a CBD-based medication, in individuals with CDD.
Our Services
As a leading company in the field of biological research and CRO services, our company is committed to providing diagnostic development services to develop rapid point-of-care diagnostic tests for CDD and achieve the goal of accurate diagnosis. We provide state-of-the-art omics analysis services that utilize advanced technologies to identify genetic abnormalities associated with CDD.
Platforms of CDD Therapy Development
We understand the importance of reliable animal models in the study of CDKL5 deficiency disorder. We offer a comprehensive range of animal models for CDD research. Our animal models have demonstrated key neuropathological features of CDD, providing valuable tools for studying the underlying mechanisms and potential therapeutics for this disorder.
Animal Models of CDD
- CDKL5 mutant zebrafish models
- CDKL5 mutant mouse models
With complete animal species resources, we can meet your diversified preclinical research including drug safety evaluation and pharmacokinetic analysis. If you are interested in our services, please feel free to contact us for more details and quotation information of related services.
Reference
- Van Bergen, Nicole J., et al. "CDKL5 deficiency disorder: molecular insights and mechanisms of pathogenicity to fast-track therapeutic development." Biochemical Society Transactions 50.4 (2022): 1207-1224.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.