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

Eran Nizri, Michal Irony-Tur-Sinai, Nikolaos Grigoriadis, Oded Abramsky, Gabi Amitai, Talma Brenner*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

14 Scopus citations

Abstract

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 α-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.

Original languageEnglish
Pages (from-to)42-49
Number of pages8
JournalPharmacology
Volume79
Issue number1
DOIs
StatePublished - Jan 2007
Externally publishedYes

Keywords

  • Bifunctional molecules
  • Central nervous system inflammation
  • Drug development
  • Experimental autoimmune encephalomyelitis
  • Multiple sclerosis
  • Natural immunomodulating protein
  • α-Fetoprotein

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