ACTRIMS 2022 | Potential of evobrutinib to target progressive MS

CNS compartmentalized inflammation consists of the accumulation of immune cells in discrete aggregates that are found in the meningeal space and also in areas within the parenchymal tissue in which they accumulate. And they are thought to be associated with the pathology that one sees in chronic stages of the disease.

We have developed this novel model in which we have animals and we induce the classic EAE model and these animals develop a progressive disease course late in the disease. And the animals have many features that resemble the pathology that is seen in progressive MS. In those animals we see this compartmentalized neuroinflammation, which consists of aggregates of different immune cells. Importantly, we see B-cells in there, we see myeloid cells in there and because we see that these immune elements are present, we wanted to interrogate if this model was one that will allow us to test the efficacy of novel treatments that are currently under study for progressive MS.

One of those treatments is based on the inhibition of BTK, which is an important molecule in the activation of both B-cells and myeloid cells. And the compound that we use is evobrutinib in which we see that application of this compound to the animals that have the disease results in significant improvement of clinical disease when we give it either in a prophylactic or in a therapeutic regimen. With this study, we wanted to see if that compartmentalized neuroinflammation could be targeted. And our findings show that indeed evobrutinib plays an important role in targeting that, and it is reflected in the clinical improvement of the animals.

So we believe that these studies show that BTK inhibition is a pathway or is a strategy that can be used to target the disease in these stages. Now we need to study down the line how BTK is affecting the immune cells that are part of that compartmentalized neuroinflammation, which at the moment we don’t know yet.