Rasmussen’s Encephalitis Drug Development

Treatments for RE include steroids, tacrolimus, azathioprine, and intravenous immunoglobulin (IVIg). Recently, treatments with monoclonal antibodies are being trialed. Equipped with extensive expertise and state-of-the-art technologies, Creative Biolabs offers a full range of optional solutions for developing a novel and effective therapy for RE.

What is RE?

RE is a rare chronic neurological disorder affecting one hemisphere of the brain. It is characterized by progressive neurological and cognitive deterioration, unilateral inflammation of the cerebral cortex, and drug-resistant epilepsy. This disease generally occurs in children under the age of 15. It also occurs in adolescents and adults. Although the underlying cause of RE remains unknown, increasing evidence suggests autoimmune or inflammatory processes contribute to the pathogenesis. Immunological studies reported cytotoxic T cells, mostly CD8-positive T cells play a major pathologic role in RE. The cytotoxic CD8+ cells attack neurons and astrocytes after recognizing unknown antigens, inducing apoptosis of those cells and leading to progressive cerebral tissue atrophy. Besides, auto-antibodies may also contribute to the pathogenesis. Patients suffering from RE have been revealed to express several auto-antibodies such as anti-NR2A autoantibodies, anti-GluR3 autoantibodies, and anti-α7-nAChR autoantibodies. Furthermore, microglial activation and release of inflammatory mediators are also the characteristics of RE progression. They are responsible for breaking blood-brain barrier, impairing extracellular environment, neurogenesis, glutamate release, and final epileptogenesis.

Histopathology of neurodegeneration and inflammation in RE. Fig.1 Histopathology of neurodegeneration and inflammation in RE. (Varadkar, 2014)

Treatment for RE

There is no cure for RE and current treatment is aimed at reducing its symptoms. Like in any other inflammatory diseases, steroids are used first to suppress the symptoms of RE, either in a high dosage for short treatment or in a lower dose for long-term treatment. IVIg is also considered as the first-line treatment for RE, effective both in the short term and in the long term. Besides, other treatments include plasmapheresis and tacrolimus.

Now, more and more attention has been paid to assessing the effectiveness of immunosuppressive or immunomodulatory treatments. For example, there is a humanized monoclonal antibody against the cell adhesion molecule α4-integrin, has been shown to reduce T-cell ability to pass across the blood-brain barrier and improve epilepsia partialis continua and focal seizures. There is a chimeric monoclonal antibody against the protein CD20 primarily on the surface of B-cells, has been shown to suppress antigen presentation and result in less T-cell activation, thereby relieving the symptoms of RE. In addition, drugs that target T and B cells, microglia, and excitotoxicity are also being investigated.

Our Capability

Leveraging advanced and well-established antibody development technologies such as phage display library construction and screening and hybridoma cell technique, we support one-stop monoclonal antibody development for RE treatment. Besides, we also support bispecific antibody development for RE treatment according to your special requirements. Most importantly, we can customize optimal cell therapy development solutions for RE treatment. For more details, please feel free to contact us to discuss your project. We are pleased to assist with the novel therapy development for RE.

Reference

  1. Varadkar, S.; et al. Rasmussen’s encephalitis: clinical features, pathobiology, and treatment advances. Lancet Neurol. 2014, 13(2): 195-205.

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