Targeted gene delivery as a novel therapeutic strategy to control inflammation in the CNS

The central nervous system (CNS) is protected by immune cells. The activity of these immune cells needs to be tightly regulated to maintain tissue homeostasis. This is the responsibility of tissue resident regulatory T cells (Tregs), which “turn off” activated immune cells. In neurodegenerative conditions, Treg numbers are insufficient to control the triggered immune response, leading to uncontrolled and chronic inflammation. However, the number of Tregs can be increased by exposure to IL-2. Hence, we hypothesize that boosting levels of IL-2 in the CNS will be beneficial to treat disease. Unfortunately, IL-2 is blocked from entering the CNS by the blood brain barrier (BBB). To overcome this, we plan to use a novel adeno-associated virus (AAV)-based vector, which can cross the BBB, to deliver the gene encoding IL-2 allowing local production and secretion from transduced cells. We will test this system in a model of multiple sclerosis.