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LONDON -- A drug trial intended to validate a novel theory of multiple sclerosis -- that it has its roots in ancient retroviral sequences embedded in the human genome -- came up short, researchers said here.

Patients treated with the HIV drug raltegravir (Isentress), which could suppress expression of retroviral elements, showed no differences in brain MRI lesion counts after treatment compared with a pre-treatment baseline phase, reported , of Barts and the London School of Medicine and Dentistry.

"The overall results for both primary and secondary outcomes are negative, with no apparent statistically significant outcome or trends for the treatment phase," she said in a poster presentation at the annual meeting.

But the study doesn't disprove the so-called HERV (human endogenous retrovirus) theory of MS, due to the trial's many limitations, and testing of another group's treatment approach based on the theory is proceeding.

This line of research originated with some of the first analyses of the fully sequenced human genome, which showed that a surprising amount -- up to 8% of the entire sequence -- appeared to encode retroviral proteins such as helicase and integrase enzymes like those found in HIV. These were initially considered "junk DNA" but subsequent studies showed that these sequences could be expressed under the right circumstances.

Some of these HERV proteins have been isolated from MS brain lesions. As well, links have been documented between Epstein-Barr virus infection (itself linked previously with MS risk) and induction of HERV expression.

And, separately, it has been noted that individuals with established HIV show a markedly lower rate of MS than the general population. Some researchers speculated that it is not the HIV infection that is responsible for the apparent protective effect, but rather -- since these observations were made in developed countries -- from antiretroviral treatment.

All of these observations have come together to suggest that therapies aimed at HERV expression might affect MS risk and/or the disease course.

The Barts and the London group, headed by , obtained support from Merck, which agreed to provide raltegravir for the 20-patient, 6-month study. When the trial was announced, Giovannoni told 番茄社区app that it had not been easy to find support from HIV drug manufacturers because none of them have a presence in MS therapeutics and were therefore mostly uninterested in committing significant funds to such a trial. That, as much as anything, dictated the choice of drug and the size and scope of the trial, he said.

The 20 patients, who were required to show evidence of MRI lesion activity at baseline, first underwent a 3-month observation period during which additional MRI brain scans were performed monthly. They then received raltegravir at 400 mg twice daily for 3 months while continuing to receive monthly scans.

The primary outcome measure was the number of gadolinium-enhancing T1 lesions seen after treatment versus the observational period. Secondary outcomes included new or enlarging T2 lesions and clinical measures of relapses and disability.

No differences or even encouraging trends were seen between the treatment and observational phases, either for the primary outcome or for any of the secondary endpoints, Marta reported.

Co-principal investigator , of Queen Mary University here, told 番茄社区app that the study was probably doomed by its limitations: the choice of raltegravir versus other anti-HIV agents as well as its use as monotherapy (HIV patients typically receive multidrug combinations) may not have achieved actual suppression of HERV elements. The small number of patients and short study duration also limited the researchers' ability to detect treatment effects.

Asked what the next steps could now be, given these negative results, he replied, "I don't know."

Gold said the lucrative market for current MS drugs appeared to be dissuading companies from searching for alternatives that get to the condition's actual cause. He pointed to another trial he is involved with in motor neuron disease, for which a major pharma company is providing substantial support.

That has not existed for the use of anti-HIV drugs, he said, even though a secondary analysis of the raltegravir trial data confirmed that HERV protein expression correlated with MS lesion counts. "It's really a shame," he said.

But this is not the only test of the HERV theory underway. Another group based in Switzerland has also been pursuing a direct anti-HERV strategy, employing a monoclonal antibody called GNbAC1 that binds to a particular expressed HERV protein.

Sponsored by Geneva-based GeNeuro SA, a phase 2b study is now underway and has enrolled half of its projected 260 patients with relapsing-remitting MS, the . As in the raltegravir trial, its primary outcome measure is T1 lesion counts assessed over 6 months. However, secondary outcomes will include clinical measures to be evaluated at 48 weeks. Multiple drug doses will be tested as well. Participants must have had at least one relapse in the past year or show at least one gadolinium-enhancing T1 lesion in the past 3 months.

A pilot trial of GNbAC1, reported in spring of 2014, found that the drug stabilized lesion counts in patients with established MS.

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