Phase II data that rolled out from Merck KGaA with its Bruton's tyrosine kinase (BTK) inhibitor evobrutinib in relapsed multiple sclerosis (MS) put more eyeballs on the mechanism. It’s already well validated in oncology, but resistance has arisen there, and at least two firms – Beigene Ltd. and Nurix Therapeutics Inc. – are striving for solutions with degrader candidates.

Tumor necrosis factor (TNF) has been implicated in the pathogenesis of several neurological disorders, such as multiple sclerosis (MS). Its transmembrane form activates the type II tumor necrosis factor receptor (TNFR2), functioning via cell-to-cell contact. In contrast, its soluble form activates TNFR1; studies in animal models have evidenced TNFR1 to activate neurotoxic pathways, while TNFR2 activation pathways may have protective effects within the central nervous system due to activation of reparative mechanisms.

Researchers from the University of British Columbia presented data from a study that aimed to define the role of nuclear receptor subfamily 1 group H member 3 (NR1H3) in the pathophysiological mechanisms that drive increased risk, severity and progression in multiple sclerosis (MS).

Researchers from Georgetown University presented data from a study that aimed to assess the intrinsic mechanisms by which myeloid cells regulate their activation states during remyelination and to identify new therapeutic targets for multiple sclerosis (MS).

Previous research has suggested that neurons in multiple sclerosis (MS) exhibit metabolic exhaustion, believed to be caused by chronic hyperexcitability, which can lead to neurodegeneration. Researchers from Heidelberg University and affiliated organizations aimed to investigate the role of nodal Kv7 (outward rectifying) and perinodal oligodendroglial Kir4.1 (inward rectifying) channels as potential therapeutic targets for neuroprotection through balancing of neuronal excitability caused by inflammatory demyelination.

Current therapies for multiple sclerosis (MS) focus on targeting immunomodulatory mechanisms...

It was previously demonstrated that the CNS-penetrant compound bryostatin-1 (bryo-1) exerts an immunomodulatory effect on myeloid-lineage innate immune cells in the periphery through its actions on protein kinase C (PKC). In a new study, researchers from Johns Hopkins University aimed to assess the potential of bryo-1 for the treatment of progressive multiple sclerosis (MS) by investigating its effect on remyelination.