the central nervous system (CNS) –the brain and spinal cord.
MS is a chronic neurodegenerative disease in which a person’s immune system causes damage to the brain and spinal cord.1,2 It results primarily from damage to the myelin sheath: a protective, insulating layer surrounding the long, thread-like part of nerve cells called the axon. Axons transmit nerve impulses in the brain, and the myelin sheath enhances conduction.
Damage to the myelin sheath is called “demyelination”. MS can also cause axons to be cut off from the rest of the nerve, which alters conduction in that part of the brain.3,4 These degenerative processes can start early in MS, before symptoms are observed.5
Immune cells that cross the blood-brain barrier trigger inflammation and destroy brain tissue
White blood cells called B-cells and T-cells contribute to MS, both independently and by interacting with each other.6,7,8,9,10,11 Antibody-producing B-cells, T-cells, and other immune cells can cross the blood–brain barrier and attack tissues in the brain and spinal cord.
B-cells also release substances called cytokines that trigger inflammation, both within the CNS and outside it. Scientists believe this inflammation contributes to MS.12
In more advanced MS, activated B-cells and other immune cells can form clusters in the lining of the brain. This can contribute to disease progression.13
Immune activity in the CNS can be seen as lesions in the brain. Damaged axons in these lesions can be re-myelinated, become inactive without being remyelinated, or continue to degenerate (“smolder”).14
Immune cells in the brain respond to the injury, causing further damage
When neural tissues are destroyed, they produce debris that attracts the attention of immune cells that reside in the CNS, including microglia.15
Microglia can be beneficial: they patrol the CNS for plaques, damaged neurons, and pathogens that need to be cleaned out. In MS, what starts out as a protective function becomes a destructive one: the debris from demyelination causes microglia to go into overdrive.16 They trigger inflammation, contribute to myelin destruction, make it harder to create new myelin, and damage axons.17,18
Demyelination (green) leaves debris in its wake. Microglia (pink)–immune cells that patrol the central nervous system–respond
Most current treatments target cells outside the brain
The blood–brain barrier protects the CNS and is extremely selective about what molecules may pass. Current therapies can limit unwanted T-cells and B-cells from entering the brain. Most MS treatments, for example antibody therapies, are designed to target cells outside the CNS, which can affect some activity inside the brain.19
However, as we understand more about MS and its processes inside the brain, we are learning about specific targets in the brain that have previously been inaccessible.
Scientists are investigating therapeutic molecules that could cross the blood–brain barrier
Creating an effective treatment that can cross the blood–brain barrier to act directly on immune cells in the CNS is a long-standing challenge in drug development. The therapeutic molecule must have certain chemical properties that allow it to evade the protective processes that exclude small molecules from entering the brain.
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