Italian physician Paolo Zamboni has publicly concluded that a therapy he developed and dubbed “the liberation treatment” does not cure or mitigate the symptoms of MS.

What many hope will be the final chapter in an unfortunate saga in multiple sclerosis research appears to have been written by the scientist who started the affair in the first place.

Italian physician Paolo Zamboni has publicly acknowledged that a therapy he developed and dubbed “the liberation treatment” does not cure or mitigate the symptoms of MS. A randomized controlled trial — the gold standard of medical research — he and other Italian researchers conducted concluded the procedure is a “largely ineffective technique” that should not be recommended for MS patients.

The trial’s result comes as no surprise to neurologists, most of whom felt Zamboni’s theory lacked plausibility from the moment news of it exploded through the MS community in 2009.

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Many of those same neurologists, though, saw their relationships with their patients fractured as belief in the liberation therapy took hold in the community of patients and their families in Canada, parts of the United States, and farther afield. Doctors advising caution against a procedure that hadn’t been proved to work or even to be safe were derided as standing in the way of innovation to protect their own practices.

Dr. Jock Murray, an MS expert and retired professor from Dalhousie University in Halifax, Nova Scotia, said the history of MS is laden with incidences like the Zamboni episode — though he said this one lasted longer than most.

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“Belief always trumps evidence,” Murray told STAT in an interview Monday.

Zamboni, who works at University of Ferrara Hospital, did not respond to STAT’s email inquiry about the trial.

The vascular surgeon was moved to look for the cause of MS because his wife suffers from the disease. In 2009, Zamboni published a paper suggesting the neurological damage the condition causes was triggered by pooling of blood in the brain that was the result of inadequate drainage.

He called the condition — which he said was common among MS patients — “chronic cerebrospinal venous insufficiency,” or CCSVI.

Zamboni further suggested inserting stents — which are designed to hold open arteries — into veins in the neck would increase blood drainage and improve symptoms.

His 2009 study appeared to show it worked, though skeptics were quick to note major flaws. There were no controls — a group that didn’t get the treatment to use as comparators — and both the patients and the doctors knew everyone was treated. A study of this kind is open to the placebo effect and to researcher bias — both of which can result in individuals seeing something they hoped to see.

Zamboni’s recently published study is the type his critics would have liked him to have done the first time — a double-blind randomized controlled trial in which neither patients nor the researchers assessing whether there were improvements post-treatment knew which patients got the actual procedure and which received a sham therapy.

The Italian researcher’s 2009 claim received some prominent and unchallenging coverage from a couple of major Canadian media outlets, and the clamoring for the procedure began.

“These patients looked like they were miraculous. And that got played over and over and over. Within 72 hours, everybody in Canada — all the patients and their families — knew about this new procedure,” said Murray. “So there was a great demand then for everyone to seek it out.”

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Patients weren’t willing to wait for science to conclude if Zamboni was correct or if his treatment was safe. Clinics sprang up in a number of countries — Poland, Costa Rica, and India among them — offering the controversial procedure. Many came home rapturously claiming benefit, only to see what others suggested was a placebo effect wane over time. A few people who underwent the procedure died.

Patients pressured the MS societies in the U.S. and Canada to advocate for access to the treatment, and in Canada, there were strident calls for the national health care system to pay for the procedure.

Meanwhile, the scientific community scrambled to try to test Zamboni’s theory and the procedure. Study after study concluded his idea was wrong. In fact, a key study in 2014 concluded that the neck veins of MS patients were no different from those of people who don’t have the condition. But disproving a theory takes time. And hope dies reluctantly.

Millions of dollars were spent trying to see if Zamboni was correct. Untold research hours were diverted from other lines of MS inquiry. Previously collaborative relationships between doctors and patients, as well as patients and the foundations set up to advocate for their needs, were damaged, Murray said. “It caused a lot of trouble.”

Earlier this year, Canadian researchers reported on a large, randomized double-blinded study — the kind designed to protect against researcher bias and the placebo effect — they had conducted on the liberation treatment. The results, presented to the Society of Interventional Radiology’s annual scientific meeting in March, showed the technique didn’t work. The study is currently under review at a top-tier medical journal, lead author Dr. Anthony Traboulsee, an associate professor of neurology at the University of British Columbia, said Tuesday.

“We hope these findings, coming from a carefully controlled, ‘gold standard’ study, will persuade people with MS not to pursue liberation therapy, an invasive procedure that carries the risk of complications, as well as significant financial cost,” Traboulsee said at the time of presentation.

And now, Zamboni’s paper showing the same has been published in JAMA Neurology.

The liberation treatment is one in a long list of therapies that have been embraced by the MS community but were ultimately found to be ineffective, said Murray. Hyperbaric oxygen chambers, snake venom, anti-coagulants, histamine desensitization therapy — all have had their turn.

The particular nature of MS — for a lot of patients, symptoms worsen, then ease before worsening again — makes it easy to appear as if a treatment has had a benefit, Murray noted.

He worried about the impact these episodes have on the MS community. “To have one after another fail, of this kind of thing, is very disheartening. And then they don’t know who to believe.”