Time to liberate ‘liberation’ therapy from MS

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Last weeks cancellation of a clinical trial in Albany, N.Y., researching treatment of CCSVI is a big setback for those trying to glean scientific insight into whether venous angioplasty mitigates multiple sclerosis (MS) symptoms in people with MS who have obstructed venous flow. Its very bad news for the Saskatchewan government, which allocated $2.2 million to fund the trial and recruited volunteersto travel to the U.S. And it is a major blow for those whod taken part in the trial or were lined up to go. But, like all failures, its also instructive. And the lesson here? That the best thing for CCSVI research, moving ahead, would be for the so-called liberation treatment to be liberated from MS itselfmore specifically, from its exclusive relationship with the degenerative condition,a point CCSVI activists have been making for years.

For those not up on the medical drama, heres a recap: In 2006, Italian venous specialist Paulo Zamboni posited a new condition hed identified as cerebro-spinal venous insufficiency, or CCSVI, was closely related to MS. Typically, vascular experts dont have anything to do with MS; neurologists are the traditional MS gatekeepers. The only reason Zamboni was investigating it was because his wife was afflicted. (That said, MS had been linked to the vascular system in medical research before famed French neurologist Jean-Martin Charcot classified it in 1868, but a correlation had never been proven.) Employing ultrasound technology, Zamboni saw a condition in the extra-cerebral veins with similar markers to venous insufficiency in legs, a condition routinely treated. Left untreated, venous insufficiency in the legs can lead to serious debilitation andmedical complications. Zamboni found CCSVI treated by angioplasty reduced, and even eliminated, symptoms experienced by people with MS.

When CCSVI made big headlines in Canada in 2009, it was as a cure (without the corroborating science) for MS, not as a separate vascular condition linked to neurodegeneration. That swept it into the MS infrastructure, a research-pharmaceutical complex populated by neurologists and MS societies that is currently based on the unproven theory that MS is an autoimmune condition. The autoimmune theory, taught in medical schools, has buttressed decades of research and given rise to a drug industryestimated to grow to $20 billion by 2017. So it isnt surprising that most MS neurologists were skeptical, even dismissive, of CCSVI from the get-go. (Imagine BlackBerry execs being asked to critique the first iPhone, and youll get the idea.) Provinces refused to cover scanning or treatment of CCSVI, making the valid point that they couldnt cover every unproven treatment simply on the basis of patient advocacy. (Provinces do, however, cover treatment for venous insufficiency in legs, and for angioplasty of extra-cerebral veins for other conditions.) When MS patients began travelling offshore for treatment in the hundreds, and then thousands, then militating at home, the government, neurologists and MS societies acquiesced and agreed to double-blinded randomized clinical trials, the cornerstone of drug approval. Clinical trials for drugs are themselves a huge industry, particularly in the lucrative MS drug arena,with neurologists being paid upward of $5,000 for every patient recruited.

The clinical-trial process has been underscrutiny of late,criticized for lack oftransparency, suppression of negative data, evenwhether they work at all. The issue of making medical treatments conform to a drug model has also raisedethical concerns.Many treatments, including angioplasty, are introduced without them. Just last year, the Ontario government gave special dispensation for some patients to receiverenal denervationtreatment,an experimental procedure to reduce blood pressure for patients who dont respond to drugs. It was backed by onlyone studyof 106 patients funded by a medical-device company poised to profit from its introduction. The Canadian Medical Association, quick out of the gate to say CCSVI must be based on science not hope,called the unproven renal denervation treatment a medical breakthrough, despiteconcernsvoicedwithin the medical community. But renal denervation treatment differs from CCSVI treatment for MS in significant ways: It didnt challenge any medical orthodoxies or interfere with pharmaceutical therapies.

Tethering CCSVI to MS created an either-or equation. Either CCSVI caused MS or it didnt. Either CCSVI was found in people with MS exclusively or it wasnt. Either CCSVI could cure MS or it couldnt. Any potential benefit in new insight into the understudied role of the venous system in neurodegeneration was eclipsed. Caught in the middle were people diagnosed with MS, a widely heterogeneous condition, with no cure.MS drugs, which run as high as $60,000 per patient per year, and whose side effects includedeath, have failed many. Now, studies indicate the drug approval has been based on benchmarks that have not beenvalidatedand that, contrary to claims,they areineffective at halting progression.

The provinces varied responses to CCSVI reflected an increasinglydecentralizedmedical systemOntario ignored it, while New Brunswick set up a fund to subsidize MS patients travelling offshore for treatment. Newfoundland and Labrador funded a smallobservational studybased on patients whod travelled to various clinics that reported in 2012 no measurable change in MS symptoms. The fedsflip-floppedbefore finally announcing in 2011 that they would fund phases I and II of a Canadian clinical trial, with 100 people to look at safety and efficacy. That trial began recruiting patients this year, with results expected by 2016 at the earliest.

Saskatchewan was the first province to pledge actual clinical trials, putting up $5 million and issuing a call for proposals in October 2010. WhenPremier Brad Wallannouncedhis government was sending 86 patients to the U.S. to participate in a phase III clinical trial in January 2012, it was a rogue move destined to resonate in the province thats home to Canadas highest incidence of MS. But there was also irony: The home of Canadas much-vaunted universal health care program had to ship residents out of country for medical research.

Now, two and a half years later, that research is kaput. The trials principal investigator, interventional radiologist Gary Siskin, needed 197 participants for the study to have statistical credibility. But only 23six from Canada, 17 from the U.S.had participated. Others were lined up to come. The problem wasnt Saskatchewan, Siskin tellsMacleans. They were confident that they could get their 86. It was me who was not confident we could get the rest. Failure to do so posed ethical concerns about making people travel and receiving funding, without confidence theyd be able to produce a statistically valid study, he says.

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Time to liberate ‘liberation’ therapy from MS