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Cell therapy targeting Epstein-Barr virus tested in progressive MS

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Summary

The Epstein-Barr virus (EBV) is a very common virus infecting 90-95% of the general population.  Research suggests that infection with EBV has a role in the development and subsequent progression of MS.  If this is the case, then treatments which target EBV might be able to prevent MS from getting worse.

In the first study of its kind, Australian researchers tested the feasibility and safety of a new cell-based therapy which targets EBV in ten people with secondary and primary progressive MS.  Blood from each person was treated in the lab to recognise and kill EBV-infected cells.  The blood was then given back to participants in four infusions over an eight week period.  Participants were monitored for 27 weeks with a range of tests including changes in EDSS, fatigue, quality of life and thinking and memory skills.

The treatment was well tolerated with no serious side effects.

Seven of the ten participants had improved symptoms starting 2 to 14 weeks after the first infusion.  Three of these had an improvement in level of disability.  Improvement occurred in people with both primary and secondary progressive MS.

Fatigue improved significantly for the whole group over the 27 week period, particularly for five of the seven participants who showed improvements. 

Participants whose T cells showed a stronger ability to attack EBV-infected cells were more likely to improve with the treatment than those whose T cells showed a weaker response.

The results confirm the feasibility and safety of the new treatment.  The improvements seen in this small study are encouraging but will need to be confirmed in larger studies which compare the cell-based therapy with a dummy, or control, group.  The biotechnology company which collaborated in this study is drawing up plans for further studies.


Background

The Epstein-Barr virus (EBV) is a very common virus infecting 90-95% of the general population.  Most people won’t know they have been infected as symptoms are generally very mild, although in some teenagers it causes glandular fever (mononucleosis).  EBV infects a subset of white blood cells in the immune system called B cells. The infected cells are usually kept under control by another type of white blood cell called killer T cells which kill virus-infected cells.

Research suggests that infection with EBV has a role in the development of MS.  Many people are infected with EBV but only a few go on to develop MS, so other factors are thought to be involved including a genetic susceptibility, lifestyle (smoking, diet, obesity) and environment (sun exposure, pollution).  These factors may combine in ways we don’t fully understand to weaken T cell control of EBV-infected cells.  This could lead to a build-up of EBV-infected B cells in the brain and spinal cord and trigger the abnormal immune attack which causes damage to the myelin coating of nerve cells. 

If this theory is correct, then treatments which target EBV should be able to kill the infected cells and prevent MS from getting worse.  Researchers in Australia have begun to test this using a cell-based treatment which targets the EBV-infected B cells.  The main aim of the study was to test the technology for growing T cells primed to kill EBV-infected cells and to evaluate safety and tolerability of the therapy. 

How this study was carried out

Australian researchers recruited five people with secondary and five with primary progressive MS.  Participants had been diagnosed with MS for between 3 to 25 years and all had experienced disability progression for at least 2 years, with EDSS scores of 5.0 to 8.0.

Blood was taken from each person and treated in the laboratory to stimulate the formation of T cells primed to kill EBV-infected B cells.  The stimulated T cells were then given back to participants in four infusions, two weeks apart, with the dose increasing each time.  Each participant was monitored for 27 weeks with a range of tests including changes in EDSS, fatigue, quality of life and thinking and memory skills.

What was found

First and foremost, the treatment was well tolerated with no serious side effects.  One person experienced a temporary alteration in their sense of taste, thought to be due to one of the chemicals used in the preparation of the cells.

Seven of the ten participants either reported or showed measureable improvements in symptoms starting 2 to 14 weeks after the first infusion, accompanied by a reduction in EDSS score in 3 participants.  Improvement occurred in people with primary as well as secondary progressive MS.

Fatigue improved significantly for the whole group over the 27 week period, particularly for five of the seven participants who showed improvements. 

Thinking and memory skills were unchanged over the period of the study.

The researchers found participants whose T cells showed a stronger ability to attack EBV-infected cells were more likely to improve with the treatment than those whose T cells showed a weaker response.

What does it mean?

The results showed that the technology was capable of growing T cells primed to kill EBV-infected cells and that the therapy was safe and well-tolerated. 

This was a very small trial and participants were followed for just 27 weeks, so it’s too early to draw firm conclusions from the results.  The improvements seen in this study are encouraging but will need to be confirmed in larger studies which compare the cell-based therapy with a dummy, or control, group.  The biotechnology company which collaborated in this study plans to carry out a randomised controlled trial of this treatment and is also testing an ‘off-the-shelf’ version, which uses immune cells from donors, in progressive and relapsing MS.

Pender MP, et al.
Epstein-Barr virus-specific T cell therapy for progressive multiple sclerosis.
Journal of Clinical Investigation Insight 2018;3(22). Pii: 124714
Abstract 
Full study 

More about developing new treatments for MS

On average it takes 10-15 years for a new treatment to get from the test-tube into the medicine cabinet. Only a few of the new treatments tested in the laboratory make it through the drug development process.

A new drug that shows potential will be put through a battery of laboratory and animal tests before being given a clinical trials authorisation that allows it to be tested in humans.

Phase I:
The first step in testing a new drug is to determine the safety of single doses in a small number of healthy volunteers.

Phase II
If the treatment proves to be safe, studies begin to determine the effectiveness of the drug in people with the condition to be treated.

Phase III
If a drug shows effectiveness, a larger study is conducted in hundreds of people.

Licensing
Data from all of these three phases is presented to the regulatory authorities.

NHS appraisal
Once a new medicine has been licensed, drugs may need to be appraised by NICE for England and Wales and SMC for Scotland.

Read more about the drug development process.

Read more about drugs in development

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Work

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