As measles cases surge to record levels in the U.S., Department of Health and Human Services (HHS) Secretary Robert F. Kennedy Jr. has downplayed the effectiveness of the long-used vaccine and instead promoted the development of new treatments for the virus.
But any new treatment would actually be a first treatment—there are no approved drugs for measles and no investigational treatments currently in clinical trials.
“Once the patient presents with major clinical signs of measles, there is only supportive care,” Richard Plemper, Ph.D., a biomedical scientist at Georgia State University in Atlanta, told Fierce Biotech. “We do not have a direct-acting antiviral that would prevent virus replication.”
That isn’t for lack of trying. Plemper has spent decades working on antivirals to treat paramyxoviruses, the virus family that includes measles and other serious pathogens like mumps and Nipah virus. His research group has developed compounds that have shown promise at halting measles virus replication in animals, but only if given soon enough after exposure.
No drug, though, can ever replace vaccination, Plemper said.
“We do have a safe and efficacious vaccine,” he emphasized. “We do not develop antivirals as an alternative.”
“Honestly, in the early 2000s we seriously thought that by now measles would be eradicated,” Plemper said. A virus closely related to measles that infects cattle called rinderpest was successfully eradicated in 2011 after a massive vaccination campaign. Rinderpest and smallpox are the only two infectious diseases to be completely wiped out.
Of the many barriers to measles drug development, one of the biggest has to do with how the disease works. The symptoms from a measles infection aren’t caused by the virus itself but rather by the immune system’s reaction to the virus, what’s known as immunopathogenesis.
That means when a patient is really sick, the actual virus is already immune-controlled and virus levels are dropping, Plemper explained. If that patient then received an antiviral (and again, none exist) to stop the virus from replicating, “that has very little advantage for the patient, because at that point, the ship has sailed."
Other major impediments to a measles drug are the lack of economic incentives and tricky clinical trial logistics. With an effective vaccine and still relatively small market size—the record-setting number for this year so far is 1,288 cases—there isn’t much incentive for pharmas to invest in developing new measles drugs, Plemper said.
And even if a company did have a measles asset, running a clinical trial would be ethically and methodologically fraught.
Because there is a measles, mumps and rubella (MMR) vaccine that works well, it would be unethical to withhold the vaccine and purposefully infect people with measles to test a new drug. And measles mainly affects children, who can’t give informed consent to participate in any clinical trial, much less one that involves being infected with a potentially deadly disease.
“Children cannot volunteer. Parents cannot volunteer their children, for good reason,” Plemper said. “So, how to actually run a phase 2 trial? That is a major deal breaker, because if you cannot advance your compounds through clinical testing, you just cannot develop a drug.”
“A” for effort
A purported treatment for measles promoted by RFK Jr. is vitamin A, which can be found, among many other sources, in cod liver oil supplements that the health secretary has touted. Experts have widely debunked RFK Jr.’s claims, and his own agency endorses vaccination over vitamin A.
“CDC continues to recommend MMR vaccines as the best way to protect against measles,” an HHS spokesperson told Fierce Biotech on July 10.
The Centers for Disease Control and Prevention (CDC) website states clearly that “vitamin A does not prevent measles and is not a substitute for vaccination.”
The vitamin can, however, be used in the management of measles for select cases, but not because it has any effect on the virus itself, Plemper said.
“If there's malnutrition, a vitamin A deficiency, then indeed, the literature supports there is some benefit,” Plemper said. “If the child has no vitamin A deficiency, which really is the case for almost every child in the U.S., then there is no advantage of vitamin A.”
Attempting to use vitamin A in place of vaccination can also prove harmful. Some unvaccinated children in west Texas, the epicenter of the current outbreak, have suffered liver damage from being given too much vitamin A in an apparent effort to protect them from measles, according to a report from The New York Times.
Unlike vitamin A, Plemper’s potential measles candidate stops paramyxoviruses from replicating, at least in animal models. He works with polymerase inhibitors, which block the machinery the virus uses to copy its genome. One of the molecules, GHP-88309, is broadly effective against multiple paramyxoviruses, including measles.
Plemper’s team infected ferrets with canine distemper virus—a surrogate since measles only infects humans—and then treated them with polymerase inhibitors at different time points. Treating ferrets when symptoms start to develop, which is typically around the three to five days after exposure to the virus, stopped the virus from replicating and protected the weasels from succumbing to the disease.
If a polymerase inhibitor is given early enough after exposure, or “at the onset of fever,” Plemper said, “then any further disease progression to severe disease can be prevented and the animal recovers very quickly.”
Within this narrow time window, Plemper sees hope for an antiviral to one day help treat unvaccinated patients who are exposed to measles. And, because his compounds work against other viruses, too, there is a feasible path to get them into the clinic as a treatment for immunocompromised patients who catch a parainfluenza virus, which are related to measles and currently have no vaccine to prevent contraction.
“There is precedent for clinical trials in those patients and the clinical need is clearly there,” he said.
Missing memory
One of the most insidious symptoms of measles is its ability to wipe out the immune system’s memory, causing so-called “immune amnesia.” Patients who recover from the disease are generally immune to measles for life afterward but become susceptible to other infections they’d previously been exposed to.
Though often thought of as a respiratory virus, measles actually first infects immune cells in the respiratory system. These infected cells then travel to the nearest lymph node to activate an immune response, which the virus takes advantage of to infect more immune cells, including memory B cells that form our long-term immunity, and spread throughout the body.
“It's a systemic infection,” Plemper said. “That means the virus enters the body and is not restricted to the respiratory tract, and, overall, the patient is very, very sick.”
The effective MMR vaccine and mass vaccination campaigns of the past have prompted another form of measles memory loss—people have forgotten just how serious the disease is.
“Measles is actually the most infectious virus that we have identified so far,” Plemper said. The virus acts fast and hits hard, causing fever, rash, cough and other respiratory symptoms. But the disease doesn’t always end there—the virus can also open the door for deadly pneumonia or brain swelling, which can cause permanent brain damage, as well as bacterial ear infections that can lead to deafness.
Before the measles vaccine became available in 1963, about 2.6 million people—mostly children—died from measles every year, according to the World Health Organization.
Communities in the U.S. regularly dealt with measles outbreaks that swept through the most recent generation of children who had not yet been exposed and thus had no immunity. The CDC estimates that before the vaccine, 3 million to 4 million people were infected every year, with about 500 deaths, 48,000 hospitalizations and 1,000 cases of dangerous brain swelling reported per year.
Because the country no longer regularly sees children die or become disabled due to infectious diseases like measles, the extremely small risks of the vaccine weigh heavier in parents’ minds, Plemper said.
The vaccine “fell victim to its own success,” he said. “How devastating this was: what it means to lose a child to an infectious disease, that has fallen out of memory.”