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Best treatment for multiple sclerosis may be antivirals

A scanning electron micrograph of immune cells called microglial cells (round) ingesting specialised cells called oligodendrocytes (branched) that maintain the myelin sheath around nerves, which is thought to occur in multiple sclerosis
Microglial immune cells (round) ingesting specialised cells called oligodendrocytes (branched) that maintain the myelin sheaths around nerves. This process is thought to occur in multiple sclerosis
Science Photo Library

The best treatment for multiple sclerosis (MS) might be antivirals that target the Epstein-Barr virus. Pharmaceutical companies are now being called on to develop such drugs after researchers studied the immune responses of people with and without the condition.

“There aren’t good Epstein-Barr virus drugs currently available, but they can be developed,” says Michael Levy at Harvard Medical School. “That might be the most useful specific therapy for MS in the future.”

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MS is caused by an immune attack on myelin, a fatty sleeve that wraps around nerves. The loss of myelin reduces their ability to transmit signals and can cause a wide range of symptoms, including muscle weakness. Drugs that suppress the immune system can slow the progression of the condition.

There is strong evidence that the Epstein-Barr virus (EBV), which causes mononucleosis, or glandular fever, is also the cause of MS. “I think most MS researchers now would agree that EBV plays a major role in the development of the disease,” says team member Kjetil Bjornevik at the Harvard T.H. Chan School of Public Health.

But exactly how remains a mystery. Almost everyone is infected with EBV during their childhood or teen years. It mainly infects immune cells known as B-cells, where it can remain dormant for the rest of a person’s life. But in some cells, the virus can reactivate.

The big question is why only around 1 in 1000 people develop MS when nearly everyone gets EBV. This suggests there is something different about the immune response to EBV in people who go on to develop MS, says team member Natalia Drosu at Massachusetts General Hospital. “Our question for this study was: in people with MS, what parts of EBV does the immune system respond to? And do those responses look different from people who don’t have MS?”

The team focused on immune cells known as CD4 T-cells, which circulate in the body. Although these aren’t the cells that directly attack myelin, there are multiple lines of evidence suggesting they play a role in MS, says Drosu.

The team found that, in 30 people with MS, most of the CD4 T-cells targeting EBV were specifically targeting viral proteins produced when the virus is actively replicating, rather than the proteins associated with its dormant stage. What’s more, people with MS produced twice as many of these cells, on average, as 30 people without the condition.

The researchers then looked at T-cells in 60 people with MS before and after they began drug treatments that reduce their number of B-cells. They found these treatments reduced the T-cell response to EBV almost to the levels seen in people without MS.

In addition, the team found low levels of EBV in the saliva of these people before they were treated to reduce their number of B-cells, which shows that the virus was replicating in their bodies. After treatment, viral levels dropped below detectable levels in most people.

The thinking has been that B-cells help drive the harmful immune response in people with MS, says Levy, and this is why drugs that reduce B-cell levels are effective. But the results suggest these drugs also work by eliminating B-cells infected with EBV, he says, thereby reducing the immune response caused by active viral replication. “We’re thinking that depleting B-cells is also depleting the reservoir of the Epstein-Barr virus.”

If so, targeting EBV directly with antivirals might be just as effective as B-cell-depleting drugs, but without the undesirable side effects of treatments that weaken the immune system, such as an increased risk of infections. “I think a lot of patients would prefer a specific drug,” says Bjornevik. “If we can show that an antiviral had a similar effect as the most effective MS drugs, I think there will be a big market for that drug.”

Another approach already being trialled for treating MS is using modified immune cells called CAR T-cells. While existing drugs merely reduce B-cell levels, CAR T-cells can temporarily eliminate them altogether. Dozens of people with MS have gone into remission after CAR-T treatment, says Levy.

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But EBV might linger in some other cell types and reinfect B-cells as they slowly recover in the years after the CAR T-cell treatment, he says. “Then we would need the antivirals… so we just have to wait and see.” CAR T-cells can also have serious side effects, says Bjornevik, so antivirals could be safer as well.

There are also vaccines against EBV under development. “If people don’t get infected with EBV, their risk of MS would be virtually zero,” says Drosu. “So I think vaccines are [a] very promising strategy to eradicate MS.”

But 1000 people would have to be vaccinated to prevent just one case of MS, Levy points out, so it isn’t clear if EBV would be justified for preventing MS alone. However, EBV causes many other problems, including a number of cancers, and has also been linked to other autoimmune conditions, such as lupus and rheumatoid arthritis.  

Journal reference:

Science Translational Medicine DOI: 10.1126/scitranslmed.adz6566

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Queen’s powerful smell suppresses rivals in naked mole rat colonies

A pregnant naked mole rat queen (left) and worker (right) sniff each other
Felix Petermann, Max Delbrück Center

There’s one scent to rule them all – and we now know what it is. A series of experiments has shown that a single molecule released by the queen of naked mole rat colonies prevents all the other females in a colony from breeding.

“It’s a super-contraceptive, if you’re a mole rat,” says Gary Lewin at the Max Delbrück Center in Berlin.

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Naked mole rats (Heterocephalus glaber) have a social structure like that of bees and ants, with colonies made up of soldiers and workers, and a single queen ruling each colony. Only the queen can breed, but how she maintains her long reign – Lewin’s team’s oldest queen is 39 – hasn’t been clear.

“The theory was that the queen is larger and more aggressive than the other animals, exerting her dominance through pushing and shoving,” says Lewin. “But we never found that very satisfying as an explanation.”

So team member Mohammed Khallaf, also at the Max Delbrück Center, proposed identifying the mole rat bouquet – the molecules in the air around them that create their scent. Comparing the scents of hundreds of animals revealed that only the queens produce a molecule called isopropyl myristate.

“It’s made in the reproductive organs, basically the vagina of the reproductive female,” says Lewin.

When the team sprayed isopropyl myristate daily into cages containing male and female pairs, none of the females became pregnant. Without it, almost all the females became pregnant.

Next, the team removed a queen from a colony and applied isopropyl myristate daily. There were no fights for succession and no females started breeding during the three months this was done. “We produced peacefulness,” says Lewin. “That’s probably the most dramatic experiment.”

When the team stopped applying isopropyl myristate, the high-ranking females started fighting within a week. After around three weeks one became pregnant: the new queen.

The team also showed that exposure to isopropyl myristate changes the levels of the hormones progesterone and prolactin. But they haven’t found out exactly how the molecule is detected and leads to these changes – that’s the next project, says Lewin.

The evidence for isopropyl myristate influencing reproduction is compelling, says Markus Zöttl at Linnaeus University in Sweden. “I think it’s an impressive and important study. And convincing.”

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Chris Faulkes at Queen Mary University of London is also convinced. “But the paper raises many questions, like any interesting research,” says Faulkes. These include how animals detect it, and how behavioural interactions and queen dominance interact with the scent, he says.

There is something special about isopropyl myristate, says Lewin. Isopropyl myristate is volatile, meaning it can evaporate into the air, but it’s not highly volatile, so any traces left by the queen take time to evaporate and the scent persists for at least a day.

It’s known that a queen will patrol every part of her colony, which in the wild might extend underground for 3 kilometres. “We think the reason she does that is to deposit this molecule around the colony,” says Lewin. “To make sure that every member of her colony is exposed to her scent.”

Other experiments by the team suggest the animals can consciously detect the smell. For instance, highly ranked females with a chance of becoming queen try to avoid places where isopropyl myristate is present, whereas lower-ranked animals aren’t bothered.

The team also tested a number of other species of mole rat. They didn’t find isopropyl myristate in any solitary species but they did find it in a few species whose social structure is more like that of naked mole rats. “But I would be cautious about assuming that the same pathway has a comparable function across social mole rats without direct experimental evidence,” says Zöttl.

Isopropyl myristate is also widely used in cosmetics. It is described as odourless but Lewin says some women at his lab thought they could smell something when exposed to it. A 2008 study also reported that it is released from the nipples or areolas of women during pregnancy and after childbirth.

Journal Reference:

Nature DOI: 10.1038/s41586-026-10772-5

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Global warming already causing crop losses of over $20 billion a year

The economies of countries where many people work in farming will be hit the hardest
Imago/Alamy

Global warming-fuelled heat and drought is already hitting yields of maize, wheat and soybeans to the tune of $20 billion a year, a study has estimated. This could rise eightfold, to more than $160 billion by 2100, unless we slash emissions.

While the financial losses will be greatest for big producers such as the US, the impacts will be felt most in the lowest-income countries, where the majority of the population works in farming, says Yi Ling Hwong at the International Institute for Applied Systems Analysis (IIASA) in Austria. “If you look at the least-developed countries in Africa, the impact is much bigger.” This could lead to social unrest and increased migration, she warns.

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There is great uncertainty about these kinds of projections, not least because so much depends on how farmers respond and adapt to a continually changing climate, for instance, by switching to different crops or adopting irrigation where it is possible. In fact, the whole point of this study is to raise awareness and encourage adaptation, to help ensure these projections turn out to be overestimates, says team member Kai Kornhuber, also at IIASA. “This is the entire mission of climate scientists: we make these cases for people to react, so our projections turn out to be wrong.”

The researchers started by gathering data on the yields per country of maize, wheat and soya from the UN Food and Agriculture Organization (FAO). Next, they took past climate data and calculated the drought level, using a standard approach that estimates soil moisture levels from rainfall and evaporation levels.

Past heat extremes and drought levels were then compared with the yields from 1974 to 2004 to estimate the impact of heat and drought. They then used these statistical correlations to estimate crop losses from 2007 to 2019. Their results suggest that increases in heat extremes and drought have caused a 3.5 per cent decline in yields relative to the 1974 to 2004 baseline. “Three per cent or so might not sound like much, but this is a major impact [on] the global food market, which regionally can trigger a severe crisis,” says Kornhuber.

The researchers then calculated the economic losses, based on FAO data showing how much farmers would have been paid for their produce at the time. Finally, they used the same approach to project future losses in several different emissions scenarios, assuming that some adaptation takes place.

In a high-emissions scenario, known as SSP3-7.0, global yields will fall by around 35 per cent by 2100, with annual losses rising to more than $161 billion. “The production losses caused by heat and drought are around 855 million tonnes a year,” says Hwong, who presented the results at a meeting of the European Geosciences Union in Vienna in May. “I think that is equivalent to what around 2 billion people consume over a year.”

This could be an underestimate of the full impact of climate change for a number of reasons: it’s just three crops, and it doesn’t include flood, storm or rain damage, or the possibility that shortages could lead to big price increases, as is already happening with some other crops such as coffee and cacao.

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Jonas Jägermeyr at Columbia University in New York says the study’s reliance on the statistical relationships between yield losses and extreme heat and drought could result in it overestimating the impacts by 2100. “Statistical yield models are great for explaining what’s happening now, and in the near past [or] future, but they are inherently unreliable when pushed into vastly different environmental regimes, such as high-emission climate scenarios by the end of the century.” Computer models of how plants are affected by rising CO2 and temperatures are better for projecting what will happen by the end of the century, he says.

Karine Chenu at the University of Queensland, Australia, makes the same point. “Although models are not perfect, they are better suited for this type of extrapolation.” However, her team recently released a study, which hasn’t been peer-reviewed, showing that two widely used models for wheat make large errors and are especially poor at forecasting the combined effects of extreme heat and drought.

But Kornhuber has defended his team’s use of statistical methods. “The models are remarkable tools, but some of the validation papers have suggested that they might not be super responsive to extremes,” he says. “In our project, extremes were the main focus, so we decided to establish these relationships directly through statistics.”

Reference:

EGU General Assembly 2026 DOI: 10.5194/egusphere-egu26-8148