Dravet Syndrome (DS)
Through in-depth research into the pathogenesis and therapeutics of Dravet syndrome (DS), our company provides cutting-edge preclinical research services with the goal of paving the way for personalized medicine and accelerating the translation of your research findings into clinical applications.
Introduction to Dravet Syndrome (DS)
Dravet Syndrome (DS) is a rare disease with an estimated incidence of 1:15,700. It is an early-onset encephalopathy that accounts for 1.4% of pediatric epilepsy cases. This debilitating condition typically presents itself around the first year of life with repeated seizures, both febrile and afebrile, leading to developmental delays and severe intellectual disabilities later in life.
Pathogenesis of DS
SCN1A, located on chromosome 2q24.3, encodes the α-subunit of a voltage-gated ion channel, NaV1.1, and mutations in this gene account for over 80% of DS cases. These mutations, including truncating and missense mutations, typically result in loss of function (LOF), leading to haploinsufficiency. Studies have shown that LOF-causing mutations are primarily associated with the pore region of NaV1.1, contributing to the pathogenesis of DS.
Furthermore, other genes such as SCN1B, GABRG2, GABRA1, STXBP1, HCN1, CHD2, and PCDH19 have been implicated in similar encephalopathies, albeit with atypical presentations, categorized as borderline DS.
Fig.1 Scn8a is a genetic modifier of Scn1a-linked DS. (Isom, Lori L., et al. 2021)Therapeutics Development of DS
- Targets of DS Therapy Development
The primary target of DS therapy development is SCN1A, whose mutations underlie most DS cases. Moreover, research efforts have identified other potential targets such as sodium channel β subunits (SCN1B) and sodium channel Nav1.6 (SCN8A) as modifiers of DS phenotypes, offering additional avenues for therapeutic intervention. - Types of DS Therapy Development
The field of DS therapy development encompasses a range of genetic and non-genetic approaches that target different aspects of the disorder.
- Viral gene therapy using adeno-associated viruses (AAVs) has shown promise in delivering therapeutic genes to the central nervous system, including approaches like AAV9-mediated expression of sodium channel β1 subunits.
- Non-viral genetic therapies, such as antisense oligonucleotides (ASOs) and RNA-based technologies, offer targeted strategies for modulating gene expression and protein levels.
Our Services
Our company focuses on leveraging innovative genetic technologies, including viral vectors and gene editing tools, to target the root causes of DS and provide preclinical research services. Our experienced team is well-versed in developing various therapeutic modalities including small molecule drug, cell therapy , gene therapy, therapeutic antibody, therapeutic peptide, and therapeutic protein specifically for DS.
DS Animal Model Services
Our company utilizes advanced animal models of DS to better understand the disease and test potential therapies. We offer Scn1a−/− mouse models and Scn1a+/− mouse models, which accurately replicate key features of DS, including spontaneous seizures, cognitive deficits, and premature mortality. We also provide a full range of animal species to support your pharmacokinetics study and drug safety evaluation.
Our company is committed to advancing the field of DS therapy through comprehensive research, state-of-the-art technology, and a multidisciplinary approach. If you are interested in our services or require further information, please contact us, and our team will be happy to assist you.
Reference
- Isom, Lori L., et al. "Dravet syndrome: novel approaches for the most common genetic epilepsy." Neurotherapeutics 18.3 (2021): 1524-1534.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.