On shaky ground with alternative treatments to autism
Dr. Carlos Pardo was trying to head off trouble.
The Johns Hopkins neurologist and his colleagues had autopsied the brains of people with autism who died in accidents and found evidence of neuroinflammation. This rare look inside the autistic brain had the potential to increase understanding of the mysterious disorder.
It also, he knew, could inspire doctors aiming to help children recover from autism to develop new experimental treatments -- even though the research was so preliminary the scientists did not know whether the inflammation was good or bad, or even how it might relate to autism.
So when Pardo and his colleagues published their paper in the Annals of Neurology in 2005, they added an online primer that clearly explained their findings in layman’s terms and sternly warned doctors not to use them to develop treatments.
“We were concerned that the study would raise a lot of controversy and be misused,” Pardo said. “We were right.”
Over and over, doctors in the autism recovery movement have used the paper to justify experimental treatments aimed at reducing neuroinflammation.
Citing Pardo’s research, doctors have treated children with a blood product typically reserved for people with severe immune system disorders like the one known as “bubble boy” disease. They have used it to justify sealing children with autism in pressurized bags and submarine-like metal chambers. Other children have been given a drug used to treat extremely rare genetic disorders.
The causes of most cases of autism are unknown. Scientists say they do not know what has gone wrong in the brains of children with autism. There are no cures. Most physicians recommend intensive behavioral therapy and, if asked, warn parents away from experimental treatments.
Even so, studies have found that up to three-quarters of families with children who have autism try at least some alternative therapies.
Physicians and others in the recovery movement -- many affiliated with the organization Defeat Autism Now -- say their treatment protocols rest on a foundation of solid science. But the Chicago Tribune found otherwise after speaking with dozens of scientists and physicians and reviewing thousands of pages of research and court testimony.
Pardo’s study is just one example. In May, the Tribune reported on another questionable use of research. A geneticist and his son who promoted treating children who have autism with a testosterone inhibitor had based their protocol, in part, on the work of Simon Baron-Cohen, a psychopathologist at England’s University of Cambridge who has explored the role of the hormone in autism.
Yet Baron-Cohen said that the idea of using the drug this way “fills me with horror.”
Pardo said that since his paper came out he has received many questions about unproven autism treatments. He is particularly haunted by inquiries regarding powerful immunosuppressant drugs usually used on organ transplant patients, calling the idea “completely wrong.” Said the researcher: “People are abusing science for the treatment of autism.”
In 2007, a Florida physician named Dr. Dan Rossignol wrote a pre-authorization letter for multiple cycles of intravenous immunoglobulin, a blood product approved to treat children with HIV or people with severe immune disorders.
But his patient was a child with autism.
Rossignol, a family doctor not board-certified in immunology, is a star in the world of alternative autism treatments and trains physicians at Defeat Autism Now seminars.
In his letter, obtained by the Tribune, Rossignol justified the unorthodox treatment in part by writing that “a recent study out of Johns Hopkins has shown that children with autism have evidence of neuroinflammation on autopsy and [cerebral spinal fluid] evaluations.” It was Pardo’s study.
Rossignol did not mention that Pardo’s team had written in its online primer, using capital letters for emphasis, that intravenous immunoglobulin “WOULD NOT HAVE a significant effect” on what they saw in the brains of people with autism.
“THERE IS NO indication for using anti-inflammatory medications in patients with autism,” the team wrote.
Meddling with neuroinflammation could actually be a terrible mistake, said co-author Dr. Andrew Zimmerman, director of medical research at the Center for Autism and Related Disorders at the Kennedy Krieger Institute in Baltimore.
“It may actually be an attempt of the brain to repair itself,” said Zimmerman, a pediatric neurologist. Suppressing the immune response “could be doing harm.”
Intravenous immunoglobulin, or IVIG, consists of pooled antibodies separated from the plasma of multiple donors. Its serious side effects run from fevers and headaches to anaphylactic shock and meningitis. Blood is screened, but there is still a remote risk of contracting some diseases, including “mad cow” disease.
Intravenous immunoglobulin treatment can run tens of thousands of dollars and involve many hours hooked up to an IV. Children are sometimes given a sedative. Because of the side effects, the cost and the lack of evidence for its usefulness, “it is irresponsible for somebody to use IVIG as a treatment except in a scientific study designed to determine whether it is effective,” Zimmerman said.
Results from the few clinical trials that have evaluated IVIG as an autism treatment are disappointing. In 2006, the American Academy of Allergy, Asthma and Immunology examined the evidence and concluded that the treatment was “unlikely to be beneficial” for autism, its lowest rating. A national panel of experts in Canada recommended against its use for autism in 2007.
Rossignol declined to be interviewed for this story. In a series of interviews and e-mails, his associate Dr. J. Jeff Bradstreet defended the use of IVIG for autism. Like Rossignol, Bradstreet is a prominent doctor in the alternative autism movement, training more than 100 doctors and lecturing to tens of thousands.
Bradstreet said he would try IVIG on every young child with autism if he could.
“Every kid with autism should have a trial of IVIG if money was not an option and IVIG was abundant,” Bradstreet said. “It makes sense to try and would be ideal to give every young child a chance at it.”
His practice offers a playroom “infusion suite” that includes a train set, a TV and toys. “IVIG is so easy for the kids once the IV is in,” Bradstreet wrote in an e-mail.
The treatment is “extremely safe,” Bradstreet said. “In 10 years we have had no significant side effects apart from short-term headaches or fevers in about 10% of the kids.”
Bradstreet said in an interview that he had extensively discussed the Pardo paper with a co-author, Dr. Diana Vargas, at a meeting.
Vargas tells another story.
“I do not recall a conversation with Dr. Bradstreet about the topic,” Vargas wrote in an e-mail. “I agree with Dr. Pardo and Dr. Zimmerman that our study did not suggest there being a use for IVIG in autism.”
Dr. James Neubrander, a Defeat Autism Now physician in New Jersey, makes tantalizing promises to parents of children with autism.
His sleek website features dozens of video testimonials from overjoyed parents detailing the amazing results of his treatments. One is titled “Miracles DO Happen!”
At least 13 videos -- the first is “From a robot to a real boy” -- are dedicated to hyperbaric oxygen therapy. Known for treating scuba divers with “the bends,” the therapy involves sealing children in chambers under various degrees of increased pressure and oxygen.
Hyperbaric oxygen treatments are hugely expensive. Chambers can cost $20,000, and renting one can run thousands of dollars a month. A course of sessions through a physician or clinic can cost many thousands.
Neubrander said about 800 of his patients have undergone hyperbaric oxygen therapy. He estimates he has treated approximately 5,000 children with autism spectrum disorder in his career.
Advocates of the treatment speculate that hyperbaric oxygen therapy can reduce inflammation, among other effects. Neubrander ends written versions of his presentations about the treatment with a list of scientific journal articles.
His first citation? Pardo’s paper.
Neubrander was involved in a published study, led by Rossignol, that found mild pressure and mild extra oxygen led to mild improvement of some symptoms of autism. Both doctors are listed as medical advisors to the International Hyperbarics Assn. on its website, which promotes the “healing magic of hyperbaric oxygenation.”
Neither doctor disclosed that information in the study, which the IHA helped fund. Neubrander said the omission was “not a purposeful deception.”
Commenting on Rossignol’s research on the website where it was published, three prominent pediatric neurologists sharply criticized its design and analysis as having “flaws.” Rossignol, Neubrander and the other authors responded that they stand by their conclusion that hyperbaric treatment can be beneficial for some children with autism. In an interview, Neubrander said he thinks his newer protocols are even more beneficial.
Neubrander has not done studies to show his protocols work and are safe. He said he doesn’t have time to wait for science to validate the results he and parents see. Also, grants are difficult to get and clinical trials may miss subtle improvements.
“Science is slow,” he said. “I will use the safety of the science and, no, I will not throw the science out the window. But the science has to be balanced against the wisdom. And science says, ‘There is no wisdom from you, the mothers or fathers of the world, who depend on anecdote. Only science has wisdom.’ ”
However, the history of medicine is rife with treatments that physicians and overjoyed patients hailed as miracles but that, when tested in clinical trials, proved to be unsafe, worthless or both. Seeing is not always believing in medicine, in terms of both safety and effectiveness.
Few treatments are completely benign, said Dr. Steven Goodman of the Johns Hopkins Berman Institute of Bioethics.
“Even an ineffective therapy is rarely harmless,” he said, “and sometimes that harm is worse than the disease.”
And the combination of pressure and oxygen can be disastrous. In May a hyperbaric oxygen chamber at a Florida clinic exploded in flames while a young boy with cerebral palsy and his grandmother were inside. The grandmother died quickly. The child, burned over the majority of his body, died in June.
There are other safety concerns. More is not necessarily better when it comes to oxygen, said Richard Mailman, a neuropharmacologist at Penn State University College of Medicine. Breathing pure oxygen under pressure can lead to a condition known as oxygen toxicity, putting the ears, central nervous system, eyes and lungs at risk.
“For someone compromised and not getting adequate oxygen, hyperbaric oxygen therapy can be lifesaving,” Mailman said. “But for somebody who is . . . well-oxygenated, you are increasing oxygen tension, and that may not be good.”
Hyperbaric medicine researchers have developed safety protocols to avoid trouble. Neubrander said that if there were problems with the treatment, he would have heard about them.
But nobody has done long-term studies on whether it is safe for children with autism to spend dozens of hours under pressure breathing air containing higher oxygen levels.
A child in one of Neubrander’s testimonials reportedly logged 243 treatment sessions, which usually run an hour each, over four years. At least some of these sessions involved 100% oxygen.
Scientists learned the hard way that tinkering with something as seemingly innocuous as oxygen can have disastrous effects. During and after World War II, doctors often administered high concentrations of oxygen to premature babies. Oxygen was assumed to be harmless and life-giving, so no clinical trials were held beforehand.
Thousands of those babies went blind, and it was years before doctors figured out too much oxygen was to blame.
“There is a long history of therapies we thought couldn’t hurt, that could only help,” said Goodman, the bioethicist. “And we found exactly the reverse.”
Patricia Kane, who calls herself “the queen of fatty acid therapy,” initially sounds like a skeptic of alternative autism treatments. She distances herself from the Defeat Autism Now approach and says hyperbaric oxygen therapy, IVIG and chelation drugs all can be harmful.
“If you could see what happens to children when they’re given some of these crazy interventions that ruin their life, and it’s so painful,” said Kane, whose office is in New Jersey. “Parents say, ‘Patricia Kane will tell us the truth,’ and I believe parents deserve the medical truth when it comes to their children.”
One of her fans is Kent Heckenlively, a California science teacher who writes for ageofautism.com, self-described as the “daily web newspaper of the autism epidemic.” After spending “a couple of hundred thousands” on treatments, from chelation to stem cell therapy, for his daughter with autism, Heckenlively said Kane appealed to him in part because her protocol includes lab tests run by the prestigious Kennedy Krieger Institute.
“I can trust them, I think,” Heckenlively said.
Kane, who points to neuroinflammation as a feature of autism, discusses Pardo’s study in a chapter she co-wrote on autism treatments for the book “Food and Nutrients in Disease Management.”
Kane says many children with autism have a buildup in their brains of a substance called very-long-chain fatty acids. Her “PK Protocol” -- named after her initials -- is aimed at burning them off with a prescription drug, phenylbutyrate, that is normally used to treat extremely rare genetic disorders in which ammonia builds up in the body.
Side effects of phenylbutyrate include vomiting, rectal bleeding, peptic ulcer disease, irregular heartbeat and depression. No clinical trials have evaluated this drug as an autism therapy, and the idea that very-long-chain fatty acids have a role in autism is not proven by science.
Kane is not a medical doctor. When treating children with autism, she says, she works in concert with the child’s physician, who supervises treatment.
She said she holds a doctorate in nutrition that was issued by Columbia Pacific University, an unaccredited institution that was shut down after a lengthy court battle with the state of California. An administrative law judge in 1997 found that the school awarded excessive credit for prior experiential learning, failed to employ qualified faculty and didn’t meet requirements for issuing degrees.
Kane said Columbia Pacific granted her a doctorate after the school “consolidated my work,” which Kane described as “clinical work” and continuing medical education courses for doctors. Her doctorate is valid, she said, because it was issued before the university ran into problems with the state.
Last year she was the subject of a television news investigation about her work with patients with ALS, also known as Lou Gehrig’s disease. The disease, which affects motor neurons, is a death sentence.
Janine Schiller, a Pennsylvania mother, went to see Kane. “Dr. Kane flat out told her: ‘You do not have ALS,’ ” said her husband, Tim. “She told her: ‘You have a buildup of neurotoxins in your blood.’ ”
Kane’s protocol involved taking pills, medications and herbal remedies, which Kane sold, Tim Schiller said. In all, the family spent $3,000. But nothing stopped the march of ALS, and Janine Schiller died eight months after her diagnosis.
“The money was trivial compared to the false hope she instilled in us,” Tim Schiller said. “It’s a terrible thing to be preying on people who are going to be dying.”
In her work with children who have autism, Kane emphasizes that she doesn’t rely on what she calls “Mickey Mouse” labs to test for red cell fatty acids in patients’ blood. She uses the Peroxisomal Diseases Laboratory at Kennedy Krieger.
But a spokeswoman for the institute said its autism experts do not endorse the use of phenylbutyrate to treat children with autism.
“There has been no research conducted at the institute which validates the use of phenylbutyrate as an autism treatment,” Elise Babbitt-Welker, the spokeswoman, wrote in an e-mail. “Any suggestion otherwise is a misinterpretation of research data.”
Research into autism has yet to find solid answers, but there is reason for hope, said Zimmerman, a co-author on Pardo’s paper.
“In the last five years, there has been a tremendous upsurge of activity,” he said. “It gives us a lot of new prospects. I think we will solve this problem in the next 10 to 15 years.”
And though autism advocates in the movement say they cannot wait that long for answers, a lack of options isn’t a valid reason to try something, bioethicists say.
“You have a duty to make sure there is good reason to believe it might work and not hurt your child,” said Douglas Diekema, a bioethicist at Treuman Katz Center for Pediatric Bioethics at Seattle Children’s Research Institute.
It is difficult to be patient while science does its work, Zimmerman said. But, he added: “Above all, do no harm.”