Rasmussen Encephalitis
Rasmussen encephalitis (RE) is a rare, chronic inflammatory disease that primarily affects children and is characterized by progressive unilateral inflammation of the cerebral cortex. At our company, we are committed to advancing drug and therapy development services to tackle the complexities of RE.
Overview of Rasmussen Encephalitis
Rasmussen Encephalitis, also known as Rasmussen syndrome, is a debilitating neurological disorder with an estimated incidence of 1 in 1 million individuals. It typically begins in childhood and progresses over months or years, resulting in significant functional impairment. Research suggests that the immune response in RE is characterized by the infiltration of activated T cells and microglia, as well as the production of pro-inflammatory cytokines, such as interleukin-1β (IL-1β) and tumor necrosis factor-alpha (TNF-α). These immune cells and molecules contribute to the chronic inflammation and neuronal damage observed in RE cases.
Fig.1 Pathogenetic model of Rasmussen encephalitis. (Orsini A., et al., 2020)
Therapy Discovery and Development for Rasmussen Encephalitis
The development of targeted drugs and therapies is paramount in managing RE. Various therapeutic modalities have been explored, each with its own mechanisms of action and potential benefits.
| Drug | Target | Mechanism of action | Time To Market |
|---|---|---|---|
| Azathioprine | DNA | Inhibitor of purine synthesis, trough the generation of a purine analogue (6-mercaptopurine). Reduces clonal proliferation of lymphocytes. | 1968 |
| Tacrolimus | CaN | Calcineurin inhibitor. Reduces the production of IL-2, crucial for the proliferation and activation of T cells | 1994 |
| Mycophenolate mofetil | IMPDH | Inhibitor of purine synthesis, trough inhibition of inosine monophosphate dehydrogenase. Reduces proliferation of lymphocytes and their recruitment. Induces apoptosis in activated T cells. | 1995 |
| Rituximab | CD20 | Chimeric anti-CD20 monoclonal antibody. Targets B cells, inhibiting their proliferation, and reduces antibody production. | 1997 |
| Thalidomide | TNF | Indirect inhibition of NF-κ β. Inhibition of innate and adaptive immune response through multiple mechanisms. | 1998 |
| Adalimumab | TNFα | Humanized anti-TNFα monoclonal antibody. | 2002 |
| Natalizumab | CD49d | Humanized anti-alpha 4 integrin monoclonal antibody. Reduces the ability of T cells to cross the BBR | 2004 |
Our Services
At our company, we are at the forefront of advancing diagnostics and therapy development for RE, aiming to provide innovative solutions to this challenging disease. If you would like to learn more about our services, please click on the following link.
Developing reliable animal models and in vitro models is crucial for understanding the disease mechanisms and evaluating potential therapies. At our company, we specialize in the development of validated animal models that mimic the pathogenesis and symptoms of RE. These models allow us to assess the efficacy of novel drugs and therapies, providing valuable insights for clinical translation.
Humanized Animal Models
Central nervous system (CNS)-targeted inflammation, characterized by increased T cell infiltration, is a consistent immunopathology associated with RE. To replicate this immune response in our mouse model, we employ the use of human peripheral blood mononuclear cells (PBMCs) obtained from RE patients.
We offer comprehensive cell-based model development services. Our experts employ primary human brain cells, such as neurons and glial cells, derived from RE patients or healthy controls, to establish in vitro models that closely mimic the disease's characteristics.
Through precise differentiation protocols, our experts guide the development of brain organoids that exhibit a diverse range of cell types, including neurons, astrocytes, and microglia. These organoids accurately recapitulate the cellular architecture of the brain.
Our company offers comprehensive preclinical research services focused on RE. In addition to the extensive array of services and models mentioned earlier, our proficiency extends to tailoring personalized solutions and creating disease models that precisely cater to your specific requirements. We take pride in our ability to adapt and customize our offerings to meet your unique needs. If our comprehensive range of services has captured your attention, we sincerely welcome you to reach out to us without any hesitation.
Reference
- Orsini A., et al. "Rasmussen's encephalitis: from immune pathogenesis towards targeted-therapy." Seizure 81 (2020): 76-83.