The "6B" strategy: Build Back a Better Blood-Brain Barrier.

Area of Science:

• Neuroimmunology
• Vascular Biology
• Demyelinating Diseases

Background:

• Multiple sclerosis (MS) is characterized by leukocyte infiltration into the central nervous system (CNS), mediated by a compromised blood-brain barrier (BBB).
• This infiltration, alongside microglial activation, drives inflammatory demyelination and neurological deficits, including paralysis.
• Current MS therapies target the immune system, potentially leading to broad immunosuppression.

Purpose of the Study:

• To review the role of the blood-brain barrier (BBB) in MS pathogenesis.
• To present the BBB as a therapeutic target for MS.
• To introduce the "Building Back a Better Blood-Brain Barrier" (6B) strategy as a novel therapeutic approach.

Main Methods:

• Focused review of literature on BBB function in MS.
• Discussion of the role of Reelin in regulating leukocyte adhesion and CNS infiltration.
• Presentation of the anti-Reelin strategy as a therapeutic example.

Main Results:

• The BBB is compromised in MS, allowing leukocyte entry into the CNS.
• Reelin, a plasma protein, influences endothelial adhesion molecules, promoting inflammatory cell infiltration.
• The anti-Reelin strategy aims to restore BBB integrity and function.

Conclusions:

• Restoring BBB physiological function offers a potential therapeutic advantage over current immunosuppressive treatments for MS.
• The "6B" strategy, by targeting the BBB, may provide a more localized and less immunosuppressive approach to managing MS.
• The BBB represents a promising and accessible target for developing new MS therapies.