In a study have been published in the journal Neurology researchers from Charité - Universitätsmedizin Berlin and the German Center for Neurodegenerative Diseases (DZNE) using a new treatment regimen have recorded significant progress in patients with Anti-NMDA receptor encephalitis. In addition to standard treatment, patients received bortezomib, a drug known as proteasome inhibitor that has proven successful in treating patients with plasmacytoma a haematological malignancy. Proteasomes play an important role in the degradation of proteins that regulate the cell cycle, thereby regulating cell growth. Given their high rates of protein synthesis, antibody-producing plasma cells display particularly high levels of metabolic activity. This renders them as sensitive to the effects of the drug as cancer cells, and results in their death.
Five severely affected patients with anti-NMDAR encephalitis with delayed treatment response or resistance to standard immunosuppressive and B-cell-depleting drugs (corticosteroids, IV immunoglobulins, plasma exchange, immunoadsorption, rituximab, cyclophosphamide) who required medical treatment and artificial ventilation on intensive care units were treated with 1–6 cycles of 1.3 mg/m2 bortezomib
Bortezomib treatment showed clinical improvement or disease remission, which was accompanied by a partial NMDAR antibody titer decline in 4 of 5 patients. With respect to disease severity, addition of bortezomib to the multimodal immunosuppressive treatment regimen was associated with an acceptable safety profile.
"'Bortezomib is capable of treating the causes of the disease by eliminating plasma cells. This makes it a valuable new treatment option in cases of anti-NMDA receptor encephalitis that have so far proven resistant to treatment," explains Franziska Scheibe, the study's first author. The results need to be confirmed by randomized trials as is the case with all the other treatment currently used in anti NMDA receptor encephalitis patients.