Immunology of cell and gene therapy approaches for neurologic diseases

Repair and replacement strategies using cell replacement or viral gene transfer for neurologic diseases are becoming increasingly efficacious with clinically meaningful benefits in several conditions. An increased understanding of disease processes opens up opportunities for genetic therapies and precision medicine methods aiming at disease modification or repair of lesioned neurologic structures. However, such therapeutic effects may be limited or rendered ineffective by immune responses against gene products or cells used for the intended treatments. When introducing therapeutic agents into the nervous system, a set of biologic responses are inevitably triggered, which may lead to host responses that limit the intended therapeutic goals. Factors of importance include the type of vector used and origin of cells, the mode of introduction, the degree of host immunization, and any prior exposure to the agents used. It is possible to apply specific treatments that interfere with many of these steps and factors in order to limit host immunization and to reduce or eliminate host effector reactions against the therapeutic agents. This includes immune-evading design measures of the advanced therapeutic medicinal products and various immunosuppressive processes. Limited duration of specific immune modulations may be possible under carefully monitored programs.