Shortly after Cameron Harding’s one-month check-up, his mother, Alison, saw that her newborn seemed to stop moving. She’d unwrap him from a swaddle and his arms would flop to one side. He wouldn’t kick his legs or turn his head.
The diagnosis: spinal muscular atrophy. The inherited illness, which destroys the motor neurons that control movement, often kills children before they turn two. Cameron’s case was severe enough he’d probably never even have a birthday.
But when he was seven weeks old, Cameron’s parents enrolled him in a clinical trial for an experimental drug. In videos shot two months later, he could move his head and reach for a toy. No child with his condition had ever made such a recovery before.
The drug Cameron received, Spinraza, was approved in the U.S. just before Christmas and may become the first blockbuster in a novel category of drugs called RNA therapeutics, after the genetic messenger molecule from which they are constructed.
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Drugs made of RNA have been in development for more than 20 years. But Cameron’s remarkable trajectory is a sign they could be ready to join familiar pharmacy chemicals and biotech proteins as the next great class of drug types, proponents say. Spinraza was developed by Ionis Pharmaceuticals and Biogen.
“Right now, RNA therapeutics—that’s the future of medicine,” says Steven Dowdy of the University of California, San Diego, School of Medicine. Dowdy admits to being a partisan—his lab works on RNA—but says advances in chemistry have finally made this type of drug feasible. “We still have a lot of work to do, but it’s going to be huge,” he says.
Some investors think so, too. One private company, Moderna Therapeutics, has reportedly managed to raise nearly $2 billion to develop what it calls a “platform” for inventing new RNA treatments. Overall, more than 150 clinical trials under way are using RNA to treat cancer, infection, hormone problems, and neurologic diseases, including Huntington’s disease.
Inside our cells, the genes in our DNA code are translated into copies made of RNA. These copies, in turn, float into the cell body, where they serve as the information template from which proteins are manufactured. Most drugstore pills act directly on proteins. Gene therapy, meanwhile, seeks to replace DNA instructions with new ones.
What drugs like Spinraza seek to do instead is use RNA to block, modify, or add to, the existing RNA messages in a cell. The most serious challenge to this approach, says Dowdy, is that cells evolved billions of years ago to keep RNA from the environment out. Overcoming this "delivery" problem has cost company chemists many years of effort.
While the science of RNA has unfolded since the 1960s to a drumbeat of Nobel Prizes, the advance into real medicine hasn’t been quick. Ionis, then known as Isis Pharmaceuticals, got the first RNA treatment approved in 1998 to counter an eye virus afflicting AIDS patients. But the drug became irrelevant once anti-HIV drug cocktails proved successful.
RNA drugs have also been beset by serious side effects, and several have been pulled from human tests over safety concerns. In October, the biotech company Alnylam had to stop a large study of one drug, Revusiran, after unexplained deaths in volunteers being treated for a hereditary metabolic disease, ATTR amyloidosis.
Alnylam, which works with a technique for blocking RNA messages, has spent about $1.5 billion since being founded in 2002 but is still working toward its first product. In January, in a paper published in the New England Journal of Medicine, it showed that one of its drugs could lower cholesterol levels for six months with one shot.
Rachel Meyers, previously a senior executive at Alnylam, says one problem facing RNA drugs is that companies have too often tried to use them to treat diseases where other options exist. Instead, she believes, RNA therapeutics are more likely to find success in situations, like Cameron’s, that can’t easily be treated in any other way. “The dirty secret of RNA therapies is that most people are working on stuff where there is competition and there are other molecules,” she says. “It’s those ones that don’t have a good alternative where you say, ‘Oh my gosh, we can really change the world, or someone’s life, with this.’”
Ionis’s drug, which is being commercialized by its partner, Biogen, works through a mechanism called “antisense.” The drug is a chemically enhanced strand of RNA that, by matching up with a mirror copy present in Cameron’s cells, allows his body to correctly assemble a protein his nerve cells need.
Last year, two drugs that work along these lines were approved in the U.S. The other, Exondys 51, developed by Sarepta Therapeutics, was approved to treat muscular dystrophy after becoming the focus of impassioned lobbying by parents of affected boys, who prevailed on the U.S Food and Drug Administration to allow it on the market despite limited evidence of its benefits.
There are no such questions about the drug Cameron receives. Its effects are “Lazarus-like,” according to one expert, but it is not simple and is not a permanent cure. It’s delivered through a spinal tap once every four months, and Cameron will need it for the rest of his life. The cost of the injections: $375,000 a year.
“This has given us a glimpse into a future that’s really quite profound, at least in serious disorders of the central nervous system,” says Biogen executive vice president Michael Ehlers.
What happens next for Cameron is not clear. Since Spinraza just started being tested in children five years ago, doctors aren’t sure what will occur as Cameron grows older. C. Frank Bennett, senior vice president of research at Ionis, says the company is now studying the results if the drug is given even earlier, just after birth, and before symptoms start. So far, he says, these kids are meeting their developmental milestones by rolling over and crawling on time.
Cameron’s mother, an employee of a bank’s IT department, says her son is still learning to control his muscles well enough to walk. It’s “a ton of work,” she says. "If there’s anything I’ve learned this last three years, it’s that the medication is not going to work by itself. If you do not work the muscles, you will not see progress.” The toddler has a physical therapist, an occupational therapist, a speech therapist, a swim therapist, and a chiropractor in addition to “a lot of doctor’s appointments.”
Now that he’s talking a mile a minute, Cameron’s speech therapist is working to help make his words more understandable. He still hasn’t learned how to control his facial muscles. But there’s a little twitch at the corner of his mouth when he’s happy. It’s the beginnings of a smile.