Could drugs shown to successfully treat HIV also be used to quell MS? To find out, researchers explore remnants of ancient viruses locked with the human genome.



Two new studies are under way to test antiretroviral medications on multiple sclerosis (MS) patients. This research is spurred by a narrowly accepted theory that MS may be triggered by human endogenous retroviruses.



In a phase-2 study currently enrolling volunteers, scientists at the Royal London Hospital in England will be following 24 patients who had been given the antiretroviral drug raltegravir, a therapy used to help prevent HIV-positive patients from developing AIDS.



Through a separate study, the Swedish company GeNeuro Innovation has developed a monoclonal antibody called GNbAC1, which targets a protein made by multiple-sclerosis–associated retrovirus (MSRV). GNbAC1 was tested on a small group of 10 patients with two different doses administered intravenously. If approved, it will become the first monoclonal antibody to target a retrovirus in MS. Patients on this drug would receive monthly IV infusions.



HERVs Defined

In 2003, scientists at the Human Genome Project completed the daunting task of mapping all of the genes found in human DNA. During that process, they discovered that nearly 8 percent of our DNA is composed of human endogenous retroviruses (HERVs), which, according to the National Institutes of Health (NIH), "represent footprints of previous retroviral infection and have been termed 'fossil viruses.'" HERVs are the remnants of the infections of our ancestors, passed on through our genes.



These leftover bits of DNA were originally thought to be harmless "garbage" that remained dormant. However, recent research has revealed that these HERVs can become reactivated, and may play a role in several autoimmune diseases and certain cancers. HIV and herpesviruses have been definitely linked to HERVs.



Epstein-Barr virus (EBV) has long been suspected as a possible MS trigger. EBV is a member of the herpesvirus family and, according to the NIH, nearly 95 percent of all people between the ages of 35 and 40 have been infected by it. Earlier studies have shown an increase in antigens to EBV in the blood of relapsing MS patients.



Several laboratories have isolated HERV proteins in MS patients, but this provides only circumstantial evidence of the role they might play in the disease. Although theories are beginning to emerge, even proponents of the idea don't know whether HERVs cause the disease or just create a “perfect storm” in which, once reactivated, they cause the immune system to overreact, triggering MS.



The HIV-MS Connection

Julian Gold, the director of the Albion Centre in Australia, specializes in treating HIV patients. After treating one patient in particular, Gold made an astonishing observation. In a 2011 case study done in collaboration with researchers at Royal London Hospital, he described a 26-year-old Australian man who had been diagnosed with both HIV and MS in 1985. Although HIV-positive, he still did not have AIDS by 1996, the year highly active antiretroviral therapy (HAART) was introduced.



Once Gold started the man on HAART to treat HIV, his MS symptoms disappeared. "Within months of commencing HAART, all MS symptoms gradually improved,” Gold and his colleagues explained in a letter published in the European Journal of Neurology, “Within 2 years, his urinary incontinence was controlled to the extent that he stopped wearing pads and fecal incontinence resolved. He has had no MS relapses."



Based on this observation, Gold wondered if perhaps a retrovirus similar to HIV might play a part in MS.



Evidence Is Growing

A 2012 study published in the Journal of Virology showed that components of a specific HERV were detected at higher levels in people with active MS.



“It is not yet known whether HERV components play a role in launching or worsening the immune attacks on the central nervous system in people with MS, or whether they are a result of those attacks,” the National MS Society wrote, in an article in about the study. “Further studies are required to address these and other questions about these intriguing findings, and their possible implications for people with MS or other disorders.”



While some researchers are skeptical about the retrovirus connection, others, such as Gold and his colleagues, feel it’s imperative to study the possible link if we want to explore all possible triggers for MS.



And since there is no animal model for HERVs in MS, studying them poses a challenge. "Their exact role will only be obtained following appropriate clinical trials,” argued Gold in an interview with MedPage Today. “If we wait for the laboratory to give us the answer, we will all have been retired."