Understanding brain-immune interaction key to developing multiple sclerosis therapies

WEST PALM BEACH, Fla. — More than a century of scientific research has shed light on the neuroimmune interaction in multiple sclerosis, which will be key for the development of disease-specific therapies, according to Jack P. Antel, MD.

Antel, a professor in the department of neurology and neurosurgery at McGill University in Montreal, gave the Kenneth P. Johnson Memorial Lecture on the first day of ACTRIMS, during which he provided a historical overview of the scientific journey that drove the discovery of the multifaceted physiology behind MS. He also shared highlights from his talk in a Healio video exclusive interview.

Early concepts: Immune reactivity outside the brain can affect the brain

According to Antel, the genesis of neuroimmune interaction occurred in the late 19th century, when scientist Louis Pasteur attempted to find a cure for rabies. Pasteur injected affected individuals with material from the spinal cord containing active virus. When the virus was made inactive, it laid the groundwork for modern vaccines.

However, Antel noted, Pasteur recorded instances where patients sustained an inflammatory response within the central nervous system following vaccination. This physiological reaction became the basis for scientific consensus that external immune reactivity that affects the brain may cause injury or inflammation.

The medical community then asked whether this reaction was the underlying mechanism behind presence of the condition.

Initially, a model known as experimental autoimmune encephalomyelitis was developed, in which material from the brain, once injected into animal subjects, gave them a telltale immune reaction in the central nervous system.

Although lack of immune responses indicated that relapsing forms of the disease may be eliminated, it did not solve the issue of halting progressive forms of the disease.

“In the course of progressive disease, wiping out the systemic immune system does not ablate the disease,” Antel explained.

Emerging concepts: The role of cell properties within the brain

The driving forces behind the interaction between the immune system and the brain became the next question to tackle toward understanding more about the disease as well as to develop therapeutic solutions.

Researchers investigated cells within the brain, particularly glial cells, which mirror the immune system in producing necessary molecules to reduce injury and trigger immune response. Animal models have shown that these “dynamic” cells can induce injury in the brain.

Understanding these potential healing properties and attempting to modulate them to respond, Antel added, led to the first generation of therapeutics that modulate the central nervous system and positively alter the consequences of immune-brain interactions.

Development of these drugs consequently gave rise to thoughts of impacting the targets that are affected by MS disease course: cells that produce myelin, oligodendrocytes, along with axons and neurons.

Microglia and astrocytes are other types of cells that can manufacture molecules promoting remyelination, Antel said.

Future investigations

“In the context of MS, we have the exciting opportunity to look for what induces the response at the beginning, how the immune system talks to the brain; importantly how the brain talks back to the immune system,” Antel said.

Building on the scientific methods of the past 130 years, researchers can now expand their capacity to modulate immune response, devote time to developing therapies which modulate disease-specific targets and the compartment within the central nervous system itself.

Questions such as “Can we change the balance from injury to repair?” remain, but Antel asserted that further understanding of the networks within the body that interact with each other may answer whether researchers can translate that into more effective therapies.