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Could drugs that target EBV treat MS?

29 January 2025

  • Current evidence strongly suggests that infection with Epstein-Barr virus (EBV) is necessary for the development of multiple sclerosis (MS).
  • Four approved antiviral drugs were identified as potential candidates for “repurposing” in clinical trials to target EBV in MS.
  • These were selected by people with MS and scientific experts because they are safe, well-tolerated and show evidence for working against EBV.

The link between EBV and MS

EBV infection is common, affecting around 90 per cent of adults globally. However, it is almost universal in people with MS.

A landmark study in 2022 provided the strongest evidence yet that infection with EBV is necessary to develop MS. Among 10 million US military personnel monitored over many years, MS only developed in those who had been infected with EBV. Signs of nerve damage appeared several years prior to MS onset, but only after EBV infection.

In MS, the immune system mistakenly attacks the insulating layer of myelin that surrounds nerve cells in the brain, spinal cord and optic nerve.

There are several theories on the role of EBV in the development of MS. One theory suggests that the body’s immune attack against EBV also mistakenly targets the brain and spinal cord.

It is not clear yet whether EBV simply acts as an initial trigger for MS, or whether it continues to drive disease activity following the onset of MS.

However, a growing body of evidence suggests that chronic EBV infection of B cells, a type of immune cell, might be a driver of chronic symptoms in MS, such as fatigue.

Why trial antivirals for EBV in MS?

In Australia and globally, scientists are investigating various strategies to target EBV in MS. These include antiviral medications, vaccines, and cell therapies.

Antiviral drugs work by preventing viruses from making more copies of themselves (replicating). However, they don’t completely eliminate the virus from the body.

If EBV is driving ongoing disease activity in MS, the hope is that using antivirals to stop EBV replicating might help suppress MS activity.

Why repurpose drugs for MS?

The development of new drugs is an expensive process with long lead times.

An alternative strategy is to “repurpose” existing drugs. That is, to take drugs that are already approved for other uses and test them for effectiveness in a new condition.

This can bring new therapies to the clinic much more quickly, because much of the safety testing has already been done, and there is often a better understanding of the drug’s target effects and side effects.

Aspirin is one example of a drug that has been repurposed, where is can be used as a treatment for pain and inflammation, as well as cardiovascular disorders.

Despite EBV being such a common virus, there are currently no approved antiviral treatments for EBV infection in Australia.

However, antivirals used to treat other viruses are known to suppress EBV activity, both in the laboratory and in human clinical trials, offering hope.

How did the researchers select antivirals for the treatment of EBV in MS?

A new Australian study took a systematic approach to selecting approved drugs with the potential to treat EBV in MS for clinical trials in Australia.

A list of 11 approved drugs effective against EBV was developed from existing reviews of the medical literature, and detailed laboratory and clinical data on these drugs were compiled.

An expert scientific panel assessed each drug for potential effectiveness in MS and possible side effects. This panel included Australian EBV researchers, MS researchers, MS neurologists, MS clinical triallists, virologists, immunologists and international MS experts.

Information on potential side effects of the drugs, as well as how they are taken (tablets, infusion, frequency etc), was reviewed by people living with MS. This expert panel scored each drug by answering whether they would consider participating in clinical trials for three different purposes in MS: treating disease activity in very early MS, treating fatigue or treating MS progression.

Which antivirals were shortlisted?

The drugs were scored by both panels, with six of 11 drugs yielding the same highest score. A further review by the scientific panel shortlisted four drugs (famciclovir, tenofovir alafenamide, maribavir and spironolactone) that balanced effectiveness, safety and being well-tolerated for use in MS.

What’s next for people with MS?

Two Phase III clinical trials of antiviral drugs for EBV in MS, known as STOP-MS and FIRMS-EBV, are expected to commence recruitment in Australia in the first half of 2025.

These will help to answer whether antivirals are effective in suppressing EBV infection in people with MS, and whether they are effective in treating progression or fatigue in MS.

Funded by the Australian Federal Government’s Medical Research Future Fund (MRFF), and supported by MS Australia, these clinical trials are a significant step forward. Other international trials of antivirals in MS are already underway.

Stay tuned for more details on the Australian trials, which MS Australia will share on our website and social channels in the coming months.

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Could drugs that target EBV treat MS?