ARTICLE | Targets & Mechanisms

Seeking cysteines

Scripps team reveals Tecfidera's targets and how to drug them

October 6, 2016 7:00 AM UTC

In settling the question of how Biogen Inc.'s Tecfidera dimethyl fumarate (DMF) acts in multiple sclerosis, a Scripps team has identified PKCθ as a key driver, sitting atop an NF-κB pathway to immunosuppression. The results not only suggest inhibiting PKCθ directly could yield a treatment option that is safer than Tecfidera, they also reveal a new way to target the kinase without hitting the other PKC isoforms, solving a selectivity problem that has confounded drug developers, with ramifications well beyond MS.

Biogen originally developed Tecfidera as a neuroprotectant; the drug was thought to work via activation of the NFE2L2 antioxidant pathway. But Tecfidera has since come to be primarily regarded as an immunosuppressant, based on its ability to squash immune flare-ups and its poor blood-brain barrier penetration, which argues against a CNS site of action. However, how the drug suppresses immune responses is unclear. ...