MS reversed by transplanted immune cells that fight Epstein-Barr virus

In a small trial, immune cells that fight the Epstein-Barr virus have stopped the progression of multiple sclerosis, an autoimmune condition that can lead to symptoms, such as difficulty walking, that worsen over time

Transplants of immune cells that target the Epstein-Barr virus have shown promise for treating multiple sclerosis in an early stage trial. Brain scans suggest the progression of the condition was reversed in some participants, but this needs to be confirmed by larger trials.

Multiple sclerosis (MS) is caused by someone’s own immune system attacking the myelin coating that helps nerve cells conduct signals, causing a range of symptoms from fatigue to difficulty walking. In most cases, people have relapses, suddenly getting worse but then gradually improving again.

In around 1 in 10 people with MS, symptoms get progressively worse with no relapses. While some treatments can slow the course of relapsing MS, there are few treatments for progressive MS.

In an initial trial, US firm Atara Biotherapeutics gave 24 people with progressive MS injections of T-cells that seek out and destroy cells infected with the Epstein-Barr virus, the cause of glandular fever or mono. The cells are extracted from donors who had previously had an infection of Epstein-Barr virus, and are immunologically matched to avoid rejection.

In a presentation on 22 March, Atara said that 20 of the people who received the injections saw their condition either stabilise or improve. The results were also previously presented at a conference.

The phase I trial didn’t include a control group to rule out the placebo effect. But AJ Joshi, Atara’s chief medical officer, says that in addition to the effect on symptoms, MRI brain scans using a technique called Magnetisation Transfer Ratio (MTR) suggest that there was remyelination of nerve cells – that is, the myelin around them regrew to some extent.

Normally, MTR measures decline in those with progressive MS, but MTR measures increased in those whose symptoms stabilised or improved, says Joshi.

“Those who improved had a larger increase [in MTR measures] than those who did not,” says Joshi. “You can see the sign of remyelination happening very early in parallel with that clinical improvement.”

The company is now enrolling another 80 people in a phase II trial, the next step in the process of drug development in which a wider group receives treatment.

“It’s encouraging that they’ve seen improvements in MTR,” says Clare Walton at the Multiple Sclerosis Society UK. “But we’ve seen treatments look promising at phase I or even at phase II, but then when you do the large randomized trials they don’t show any outcome.”

There is, however, a lot of excitement about treatments based on tackling the Epstein-Barr virus, says Walton, because recent studies have greatly strengthened the case that the virus is a cause of MS.

In January, a study of 10 million military personnel in the US reported that infection with the virus preceded almost every case of MS. Another study, also published in January, showed that one of the proteins produced by the Epstein-Barr virus is very similar to a human protein produced in the central nervous system, and that at least a fifth of people with MS have antibodies that bind to both proteins.

In other words, in some people the immune response to this viral protein may mistakenly target this human protein as well. Since the virus hides away in people’s bodies after the initial infection and sometimes reactivates, this immune response can be continually stimulated.

If this is the case, tackling the virus should help treat all forms of MS. Atara chose to focus on progressive MS because there are few existing treatments, says Joshi.

“When you have that unmet need, you typically have a chance to progress much more rapidly through the regulatory pathways,” he says.

Joshi says there is also evidence that the Epstein-Barr virus is involved in other autoimmune conditions, such as lupus and rheumatoid arthritis, and that Atara plans to see whether its treatment helps these conditions.

MS reversed by transplanted immune cells that fight Epstein-Barr virus

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