b'Medicine & ResearchRX UpdateBBTTKKIInnhhiibbiittoorrss::AABBeetttteerrWWaayyttooFFiigghhttMMSS??By Ellen Whipple, Pharm.D. and Brittany Brooks, BS Chemistry, Pharm.D. Candidate 2022 A new avenue of treatment for MS is beingGVHD. While it works well and has had researched. What is this potential treatment?signicant progress in affecting BTK, it also How does it work? The drugs being studiedaffects other kinases and B cell malignancies, are BTK inhibitors. Lets examine what BTKleading to off-target activity and a signicant is, so we can understand how these drugsside-effect prole. This has led the pharmaceutical that inhibit it might be helpful in MS.researchers to look for alternatives with ibrutinibs Brutons tyrosine kinase, or BTK, is anefficacy but more specic targeting. enzyme that plays an important role in theThere are two types of BTKis: irreversible immune response. It transmits signals thatinhibitors and reversible inhibitors. Irreversible are critical for the activation of B cells. BTKinhibitors have a higher rate of inhibitory also plays a part in signaling in myeloid cells,potency and selectivity compared to reversible including macrophages and microglial cells.inhibitors. For research in the treatment of This signaling leads to the secretion ofMS, irreversible inhibitors have recently been proinammatory cytokines. Inhibiting BTKat the forefront because of their potential could block the activation of cell-signalingadvantages over the biologic disease-modifying pathways related to the development oftherapy options.autoimmune diseases, such as MS.These inhibitors can selectively target B-cells, BTK inhibitors, the treatments being studied,wiping out those that harm the immune systems are designed to selectively block this enzymeof people with MS while leaving normal B-cells that is important for the activation of B cellsalone. This shows an advantage over the disease- and microglia. B cells and cells of the myeloidmodifyingtherapiessuchasocrelizumab lineage are important drivers in the developmentand rituximab, as they wipe out all the B-cells, of multiple sclerosis, thus BTKi could provideleaving a greater chance of infection. Currently, therapeutic benet for MS. therearestudiesbeingconductedusing These drugs have been previously used inBTKis to aid in the treatment of relapsing-other areas of disease such as graft versus hostremitting MS, primary progressive MS, and disease, lymphomas, and leukemia. One ofsecondary progressive MS.the rst BTKis to be approved was ibrutinib.One of the newest drugs, evobrutinib, is This rst-generation drug was approved inthe rst covalent and irreversible BTKi to be 2013 for lymphocytic leukemias and chronicevaluated for the treatment of MS. Compared msfocusmagazine.org 56'