According to the National Multiple Sclerosis Society, a non-profit organisation in New York, 2.8 million people worldwide are now living with multiple sclerosis (MS). “The majority of people with this condition are diagnosed between the ages of 20 and 30, and women are more susceptible,” Dr M Netravathi, additional professor in Neurology at the National Institute of Mental Health and Neurosciences, Bengaluru, tells Happiest Health.
MS is a chronic and progressive neurological disease that affects the central nervous system (brain and spinal cord). It causes problems with vision, balance, and muscle coordination, along with symptoms like numbness, tingling, and fatigue.
Immune betrayal
When pathogens invade the body, our immune system typically unleashes specialised immune cells to counter the attack. However, in MS, immune cells mistakenly attack the protective covering of the nerves called myelin instead of foreign bodies such as bacteria and viruses, says Dr Netravathi.
“Due to this dysregulated immune response, [the] myelin sheath gets damaged, and the nerves cannot relay messages properly, so the body and brain have trouble communicating,” she explains.
The exact cause of this immune betrayal is still unknown, but active research has identified environmental factors, genetics, and infection-related agents that may contribute to MS.
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The rogue response
A recent Swedish study investigated how the Epstein-Barr virus (EBV), or human herpesvirus 4, plays a role in MS. EBV is a widespread and highly contagious virus, and almost everyone is infected by it at least once in their lifetime, after which the virus remains dormant in the body.
In the study, published in Science Advances, researchers from the Karolinska Institutet uncovered the mechanism of how an EBV infection triggers MS. “Our work focuses on the theory that the immune response to EBV – which would normally control virus infection in the memory B cell pool – instead mistakenly targets and damages the central nervous system through molecular mimicry,” Dr Olivia Thomas, the first author of the study, tells Happiest Health.
She explains that molecular mimicry is two structurally similar, but distinct antigens (immune markers) activating the same immune cell – T or B cells. While the immune system generates an immune response to fight infection, in some individuals, it goes rogue and damages the brain and spinal cord, leading to MS symptoms.
Mistaken identity
When the researchers analysed blood samples from 700 people with MS and an equal number of healthy people, they found the immune system made a mistake in identifying the correct target. In the MS samples, they saw that the antibodies that are supposed to bind to a protein produced by the EBV virus, wrongly latched to a structurally similar protein in the brain and spinal cord.
The dysregulated process caused nervous system damage, leading to severe MS symptoms. They also observed that the percentage of these antibodies was higher in people with MS than in healthy individuals.
“This also demonstrates the high variation [of symptoms] between patients, highlighting the need for personalised therapies. Current therapies are effective at reducing relapses in MS, but unfortunately, none can prevent disease progression,” Dr Thomas says in a statement.
A backpack therapy
Samir Mitragotri, a professor of bioengineering at the Wyss Institute at Harvard University, USA, says that the autoimmune nature of MS and the fact that it happens in the brain makes it hard to develop therapies that specifically access the affected region.
“Even if there was a therapeutic which can effectively reduce the disease severity, how do you get it in there? That is a significant challenge,” he says. However, he adds that developing therapies to reduce symptoms through the immune system (immunomodulation) can be a solid solution.
Prof Mitragotri and his team found a way – via the myeloid cells. “Whenever there is inflammation or infection in the body, myeloid cells are the first to respond. They infiltrate easily [at the site of inflammation] and become a part of the pathology,” says Prof Mitragotri. However, these cells can easily pass through the blood-brain barrier and penetrate deep into the tissue. Their study, published in Proceedings of the National Academy of Sciences discusses the strategy.
The team engineered the myeloid cells to carry a ‘backpack’ of anti-inflammatory molecules. This backpack can make the myeloid cells anti-inflammatory, which reduces the inflammation seen in MS. When the researchers added the backpacked myeloid cells into mice models with MS, there was a partial reversal of hind limb paralysis and improvement in motor functions.
From innovation to industry
Understanding what precisely causes MS can help in developing appropriate solutions. “If we can understand how the immune response to viral infections (like EBV) may target host proteins, we develop more targeted and personalised therapies,” says Dr Thomas.
Prof Mitragotri explains that the first stage in developing innovative therapies is to ensure their viability. “The interactions and collaborations with clinicians to understand the gap between where the solution is and what, is needed,” he says.
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