Bruton's Tyrosine Kinase Inhibition in Multiple Sclerosis.
Raphael SchneiderJiwon OhPublished in: Current neurology and neuroscience reports (2022)
There is evidence that some BTKIs cross the blood-brain barrier and may be superior to currently available DMTs at dampening the chronic neuroinflammatory processes compartmentalized within the CNS that contribute to progressive worsening in people withMS (pwMS). Recently, evobrutinib and tolebrutinib have shown efficacy in phase II clinical trials, and there are numerous ongoing phase III clinical trials of various BTKIs in relapsing and progressive forms of MS. Results from these clinical trials will be essential to understand the efficacy and safety of BTKIs across the spectrum of MS and keydifferences between specific BTKIs when treating pwMS. Inhibition of BTK has emerged as an attractive strategy to target cells of the adaptive and innate immune system outside and within the CNS. BTKIs carry great therapeutic potential across the MS spectrum, where key pathobiology aspects seem confined to the CNS compartment.
Keyphrases
- multiple sclerosis
- clinical trial
- phase ii
- tyrosine kinase
- phase iii
- open label
- epidermal growth factor receptor
- blood brain barrier
- white matter
- double blind
- induced apoptosis
- immune response
- placebo controlled
- study protocol
- cell cycle arrest
- mass spectrometry
- ms ms
- randomized controlled trial
- rheumatoid arthritis
- cell death
- endoplasmic reticulum stress
- oxidative stress
- signaling pathway