“There was this subset of kids with autism that had gut problems, and no one was focusing on that. They were just looking at the brain, and Ellen helped us realize that maybe we’ve been looking at the wrong end,” says Emma Allen-Vercoe, a microbiologist at the University of Guelph in Canada.
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Other potential autism treatments have also originated from N-of-1 trials that were subsequently expanded. In the early 2000s, researchers reported a condition called cerebral folate deficiency (CFD), which results from folate not getting into the brain and is characterized by seizures, learning difficulties and irritability. Early case reports mentioned that many children with CFD also have symptoms of autism. When a boy with possible CFD and autism showed up at Richard Frye’s clinic five years ago, Frye tested the boy for antibodies to the folate receptor protein—a test that is diagnostic for the disease. With the diagnosis confirmed, Frye prescribed leucovorin calcium, which helps transport folate into the nervous system and alleviates symptoms of CFD. To his surprise, Frye found that it also improved the boy’s autism symptoms. Based on this observation, Frye began to collaborate with other researchers to test children with autism for signs of CFD, thinking they might benefit from the treatment.
Frye asked 44 families to document their children’s symptoms before and after treatment, and used the families still waiting for CFD test results as controls. “Parents are often partners in these trials, since they typically know their children best, and are often the first to pick up on subtle changes in behavior,” says Frye. The results were published in a 2012 study showing that this treatment can also improve symptoms in children who have only autism.
“You can’t do double-blind clinical trials on everything,” says Frye. “N-of-1 trials provide an important jumping-off point. They can generate better data about what might be causing a disease and what might work to treat it.”
Researchers in other specialties have taken this approach even further. Bedlack treats people with ALS, a condition with few treatments. He sees parallels between ALS and autism that encourage experimentation. That isn’t necessarily a problem, Bedlack says, as long as there’s an open, non-judgmental conversation about the options.
“People want to believe there’s something better out there to treat their illness, but they’re hesitant to share their efforts with their doctors because there’s often a dismissive or paternalistic response,” Bedlack says.
Bedlack’s willingness to look beyond the standard, randomized controlled trial and prowl the back alleys of the internet for new ideas has given him the nickname ‘the Fox Mulder of ALS.’ People often come to him with ideas they read about online, such as coconut oil or protein supplements. Researching each option could take hours, and the process would have to be repeated for each. So Bedlack created ALS Untangled, an online forum where anyone can submit ideas for ALS therapies. Bedlack and an international team of ALS specialists then search through both medical literature and unconventional reports in what Bedlack refers to as the “dark corners of the internet.” They review the information from all their sources, and ultimately publish their conclusions in a research article that anyone can read for free.