But doctors and families of those helped so far are elated at the progress.
"This is really an important time in gene therapy," says Dr. David Williams, professor of pediatrics at Harvard Medical School and chief scientific officer at Boston Children's Hospital, who was not involved in these children's treatment, but has recently achieved similar success with another genetic condition.
Eli's mother, Natalie Wheatley, had been terrified there was something wrong with Eli even before he was born. He barely moved during her pregnancy, she recalls, and never seemed quite right in the first weeks of his life.
Finally, doctors told her that her worst fears were true: Her son had spinal muscular atrophy, a disease of motor neurons that was destroying his muscles.
"They basically told me he wouldn't make it to his first birthday," says Wheatley. Take him home and love him and spend as much time with him as you can, she remembers the health team telling her.
"I was devastated — devastated," she says.
Guardino was diagnosed with a different condition — Leber's congenital amaurosis, a disease of the eye's retina — when he was born. The disorder isn't fatal. But it was destroying his vision.
"I wouldn't be able to walk around outside on my own," says Guardino. During the day, he says, the world looked "incredibly dark" and blurry. "It was sort of like watching your world fade away."
Now Guardino can see things he'd only dreamed about.
After the gene therapy treatment, he says, "I was able to see things for the first time — like the moon. I was able to see stars for the first time – fireworks — all these amazing things that I've never been able to see before."
And Wheatley's son, Eli, seems to be thriving.
"He just started preschool in September," his mom says. "He goes to preschool alone. He eats in the cafeteria with all the other kids. He's doing extremely well. It's been amazing — truly amazing."
Recent success in these different cases "really shows us we're able to harness this therapy for some pretty terrible diseases," says Williams, who reported last month in the New England Journal of Medicine that gene therapy can also halt the progression of disease in boys suffering from adrenoleukodystrophy, a fatal genetic brain disease made famous by the movie Lorenzo's Oil.
Scientists thought this sort of success would come decades ago. But their first attempts to save people born with defective genes by giving them new, healthy genes fizzled. Some patients who volunteered for early experiments developed cancer. At least one person died.
"And that caused a setback in the field, which caused a lot of concern that maybe gene therapy was not ready for prime time," the NIH's Wolinetz says.
Some scientists feared gene therapy might never work. Researchers went back to the drawing board to come up with better, safer ways to use viruses to deliver healthy genes into a person's body. It's those decades of research that finally seem to be paying off.
"We have reached a point of maturation in the science and in some of the new approaches to gene therapy that have allowed us to make rapid advancements in a fairly short period of time," Wolinetz says.
The price tag of such a treatment remains a looming question. The first gene therapy product approved by the Food and Drug Administration (a treatment for a form of leukemia, approved last summer) costs hundreds of thousands of dollars for each infusion. Some drug industry analysts predict the next gene therapy could cost close to $1 million per patient.
Dr. Peter Bach, director of the center for health policy and outcomes at Memorial Sloan Kettering Cancer Center, says he's thrilled with the scientific progress that's been made in the field — but the cost of gene therapy drugs troubles him.
"The model by which every innovation is turned around to extract the maximum amount of profit is ultimately taking away our ability to adequately fund many other things that promote health," Bach says.
Whatever the questions and costs, people who have been helped by these treatments so far seem delighted.
"I think that the gene therapy is a miracle," Guardino says. "I can't imagine what my life would be like without it."
Natalie Wheatley, whose son Eli was among those described in another study, published early this month in the New England Journal of Medicine, says her son seems to continue to improve.
"I see progress every day," Wheatley says. "So that, to me, offers hope that gene therapy has saved his life. And I think eventually gene therapy will give the world hope. That's my hope anyways."
The FDA could soon approve for non-experimental use the first gene therapy for a genetic disorder — the treatment Guardino received to save his vision.