Novel approaches to treatment of autoimmune neuroinflammation and lessons for drug development.

Drug development, and especially that intended for central nervous system (CNS) disorders, still poses a challenge. We investigated both the use of bifunctional compounds designed for multiple targeting and enhanced CNS permeability, and of recombinant alpha-fetoprotein (AFP), a natural pregnancy-associated immunomodulating protein for the treatment of CNS inflammation. Bifunctional compounds showed a novel pharmacokinetic profile due to the conjugation, yet retained, and even improved pharmacodynamics. AFP was well tolerated and decreased various aspects of neuroinflammation, including disease severity, axonal loss and damage, T-cell reactivity, and antigen presentation. Our results show that both strategies may serve as future drug modalities. Copyright (c) 2007 S. Karger AG, Basel.