Innate and Adaptive Immunity and BTK Inhibitors for Multiple Sclerosis


Barry A. Hendin, MD, discusses innate and adaptive immunity and BTK inhibitors in the treatment of multiple sclerosis (MS).

Ahmed Z. Obeidat, MD, PhD: Dr Hendin, I want get back to you and talk a little about the Bruton tyrosine kinase inhibitors [BTKIs], or BTK inhibitors. We’re going to discuss them further today, but talk about their role in microglia in MS [multiple sclerosis]. This is one of the aspects that we’d like to hear your input about.

Barry A. Hendin, MD: Sure. I’m delighted to talk about the BTKIs. BTKI is an enzymatic approach to the treatment of MS and has some unique features. We don’t have an approved BTKI therapy, but many of them are being investigated. The hope is that it will have some unique features that our current therapies don’t have. Our current therapies are specifically directed toward the adaptive, or acquired, immune system, whereas the BTKIs work both on the adaptive and innate immune systems. That’s one of its unique features.

Also, most of our therapies are dealing with our immune system from the outside in. That’s the immune system in the blood, lymph nodes, etc. The BTKI molecules are brain penetrant, which is to say they can get into the brain. Therefore, the hope is that if they can get into the brain, they can start to deal with some of the things we haven’t been able to get to successfully with our agents that aren’t brain penetrant.

What are those things we’re hoping for? We know that in addition to the acute inflammation that occurs in MS, there’s a smoldering inflammation that’s hard to get to. That smoldering inflammation may be part of what drives late progression. If you have a new set of therapies that act on the innate and adaptive immune systems, are brain penetrant, and can deal with the compartmentalized, hard-to-reach inflammation that other therapies haven’t been able to successfully get to, maybe you have a therapy that could be initiated early and reduce progression, or initiated late in order to deal with late progression in MS. Many of us are hopeful, but we’re also waiting for the data that will emerge over the next year to fully understand this class of enzymes.

Ahmed Z. Obeidat, MD, PhD: Thank you very much. We’re going to discuss BTK inhibitors a lot more in the future segments. One of the aspects you mentioned is that so many BTK inhibitors are in the pipeline. We call it a race of BTK inhibitors. There are several of them, which is great, and it looks like each of the molecules have some differences. They’re small differences, but they may translate into some clinically meaningful differences that we may see after these studies are complete.

Transcript Edited for Clarity

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