“I wouldn’t say it’s going to be easy,” says Lieberman, who is developing antiviral drugs that target EBNA1 to knock out the latent virus. If research can decipher the contributions of both phases and how the latent virus is reactivated, it could open new doors. Another strategy is to destroy the virus’ breeding ground: the B cells. Atara Biotherapeutics of South San Francisco, Calif., is trying to do this with ATA188, a therapy designed from the immune system’s T cells to hunt down and destroy the B cells that harbor EBV.
T cells hunt B cells
A Phase I/II trial is ongoing in people with advanced MS in hopes of slowing the progression of the disease. Preliminary results are expected later this year. “If you see an effect, that means the game is on,” says Robinson. But neurological diseases are difficult to treat when brain damage is already present. T-cell therapies may be best when used at an earlier stage of the disease. But they are a new form of therapy with uncertainties – and thus an unlikely candidate for a large-scale prevention study.
Erin Longbrake, a neurologist at Yale University in New Haven, Connecticut, considered how to balance the need for early intervention with the potential side effects of treatment. Her therapy of choice is the FDA-approved MS drug ocrelizumab, which kills B cells to jump-start the dysfunctional immune system. It wasn’t designed to be an antiviral, but it disables at least part of the EBV reservoir. Because it weakens the immune system, people being treated are at high risk of other infections. So it’s a high price to pay for someone who isn’t sick. So Longbrake looked for those with the most to gain: a small group of people with damaged brain regions similar to those of MS patients but none of the accompanying symptoms. Such lesions are sometimes discovered incidentally on a brain scan. Almost half of these people will develop MS within the next ten years after discovery.
“If you told me I had a fifty-fifty chance of getting MS, I’d want to do something about it,” Longbrake says. A study examining whether ocrelizumab can slow the development of MS in 100 people with such lesions is currently recruiting. Researchers are also working to identify people at high risk for postviral complications.
Be well prepared
It could be decades before an EBV-targeted intervention can stave off MS. And while Long Covid has sparked widespread interest in the long-lasting effects of infection, verifying that there is a link between a virus and a disease is laborious. For Dobson, the key to success is good preparation and patience. Ascherio’s discovery, for example, was made possible by the Department of Defense’s decades-long collection of biological samples — an expensive method that takes years to yield insights.
“Biobanks are really complex and unpopular. But when the hard work is done, everyone loves it,” says Dobson. Similar disease diagnosis resources – collected during the pandemic – will provide insights into the long-term effects of other viruses. Work with the UK Biobank has already shown how the Sars-CoV-2 virus can affect brain structures.
Longer consideration is required for clinical trials, she adds. These would require finding the right people and means of measuring success – this is easier to do with a disease like MS, which doctors can accurately diagnose and monitor, than Long Covid, which has no clear clinical definition. Nevertheless, it is important, says Dobson: “If we don’t start thinking about these studies, we will be in the same place in 15 to 20 years.”