Persistent pursuits

CHICAGO — 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 submarinelike 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 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 told the Tribune 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.”

Study’s cautions ignored

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.”

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.

IVIG 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.

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 percent 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.

“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.”

Hyperbaric oxygen therapy

Dr. James Neubrander, a Defeat Autism Now! physician in New Jersey, makes tantalizing promises to parents of children with autism.

His sleek Web site 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. 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.

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 advisers to the International Hyperbarics Association on its Web site, which promotes the “healing magic of hyperbaric oxygenation.” Neither doctor disclosed that in the study, which the IHA helped fund. Neubrander said any omission was “not a purposeful deception.”

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.

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.