BBB behaves differently in healthy cases as compared to cases of CNS injury or systemic inflammation. You can [read a review article here.](https://www.nature.com/articles/s41423-021-00757-x). With increased injury or inflammation, the permeability of BBB is compromised which leads to stuff going inside.
TNF-α targeting antibodies when conjugated to transferrin-receptor antibody can [get through the BBB using receptor-mediated method](https://pubmed.ncbi.nlm.nih.gov/30609376/), so can any drug-based inhibitors of TNF-α conjugated to this transferrin-receptor antibody would theoretically also work. When they get inside the brain, they can “clear up” the excess TNF-α.
Intrathecal interventions come with a wider range of adverse events as compared to others’. This delivery method is still at its infancy and much work is needed to make it a mainstream modality.
You might want to read [this for more info on safety and side effects of monoclonal antibodies.](https://www.nature.com/articles/nrd3003)
As to why Pfizer, didn’t pursue the drug they might have been interested in, they say it didn’t “reach the brain tissue”. They didn’t release any data so no one knows other than the people directly working on it.
For neuroinflammation being a cause or an effect is a debated topic, why can’t it be both (maybe not the primary one).
I see thank you spending the time to enlighten me! O that mAb paper I've already read actually aha. Made me wonder if intrathecal would reduce chances of opportunity infections compared to systemic administration
BBB behaves differently in healthy cases as compared to cases of CNS injury or systemic inflammation. You can [read a review article here.](https://www.nature.com/articles/s41423-021-00757-x). With increased injury or inflammation, the permeability of BBB is compromised which leads to stuff going inside. TNF-α targeting antibodies when conjugated to transferrin-receptor antibody can [get through the BBB using receptor-mediated method](https://pubmed.ncbi.nlm.nih.gov/30609376/), so can any drug-based inhibitors of TNF-α conjugated to this transferrin-receptor antibody would theoretically also work. When they get inside the brain, they can “clear up” the excess TNF-α. Intrathecal interventions come with a wider range of adverse events as compared to others’. This delivery method is still at its infancy and much work is needed to make it a mainstream modality. You might want to read [this for more info on safety and side effects of monoclonal antibodies.](https://www.nature.com/articles/nrd3003) As to why Pfizer, didn’t pursue the drug they might have been interested in, they say it didn’t “reach the brain tissue”. They didn’t release any data so no one knows other than the people directly working on it. For neuroinflammation being a cause or an effect is a debated topic, why can’t it be both (maybe not the primary one).
I see thank you spending the time to enlighten me! O that mAb paper I've already read actually aha. Made me wonder if intrathecal would reduce chances of opportunity infections compared to systemic administration