Dr. Stephen L. Hauser is very vocal regarding his contempt for CCSVI research. As the editor of the Annals of Neurology, he has "expeditiously" (his word) published negative results that contradict Dr. Zamboni's findings, because he believes venoplasty is an unsound and dangerous practice. Yet, as we shall learn, Dr. Hauser has been a proponent for a drug therapy that has killed more than 50 patients. His studies were sponsored by the drug's manufacturer. And he has never published any negative studies on this drug.
http://bloodjournal.hematologylibrary.org/content/113/20/4834.long
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Here is a recent editorial from Dr. Hauser. Thanks to Shirley for sending the link. He can barely contain his disdain ---
The confluence of the Internet, the hope for a simple and correctible answer to a common, mysterious and untreatable problem, and well-organized patient advocacy groups, can create a “perfect storm” in which preliminary or uncertain claims are rapidly disseminated and acquire momentum well beyond that justified by the strength of evidence. A similar situation, discussed earlier in these pages, followed preliminary reports that potentially correctible venous abnormalities (chronic cerebro-spinal venous insufficiency or CCSVI) might underlie multiple sclerosis (MS). Sadly, repeated failures to replicate these original claims using carefully designed methodologies have not yet reduced the considerable attention and public interest in CCSVI, nor eliminated unsound and dangerous attempts to “repair” abnormal veins in MS patients (outrageously called “the liberation procedure”).10–12
http://onlinelibrary.wiley.com/doi/10.1002/ana.22529/full
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Dr. Hauser is a neuroimmunologist and MS specialist. In recent years he had researched Rituximab/Rituxan in MS and was a very vocal proponent for the use of this cancer drug --In 2007-08, Dr. Hauser traveled the globe for Genetech and Rituxan, speaking at ECTRIMS, AAN and neurological conferences, giving giddy interviews to the press, speaking to investors and all who would listen. All based on the results of studies he conducted at UCSF. If you search Dr. Hauser's name plus Rituxan, you can find all of the positive, glowing press and financial reports. Here's one such article--
Dr. Hauser describes his own odyssey as a clinician scientist--his path in taking a drug from the laboratory to clinical trials in people with MS. Long interested in the immune activity that underlies MS, Dr. Hauser published seminal findings associating antibodies (proteins produced by B cells) with damage to the myelin. (Nature Medicine 1999 Feb;5[2]:170-5) These lab findings resulted in a clinical trial of rituximab (Rituxan, from Genentech and Biogen Idec), a drug that depletes B cells.
"The development of rituximab has been thrilling," said Dr. Hauser. "We found that treatment was effective against relapsing-remitting MS beyond what we had imagined." Dr. Hauser and colleagues reported that one course of this intravenous drug reduced disease activity and relapses for 48 weeks in people with relapsing-remitting MS, a course of MS characterized by clearly defined flare-ups followed by partial or complete recovery periods. (The New England Journal of Medicine 2008 Feb 14;358[7]:676-88)
http://www.thefreelibrary.com/On+the+cusp+of+a+new+world%3A+MS+gene+pioneer+Dr.+Stephen+Hauser+shares...-a0187844645
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What incredible results! Almost the exact same "perfect storm" Hauser writes about in relation to CCSVI. The positive results for Rituxan from a couple preliminary studies, the media attention, the simple answer to the complexities of MS. Just suppress the b cells! Both of Dr. Hauser's studies were supported by Genentech, Inc., and Biogen Idec., the companies marketing the drug in the United States.
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Thankfully, this drug will not be approved by the FDA for MS. The patent on Rituximab expires in 2015, and there just wasn't time to get phase III trials in MS, or FDA approval. There's no money in Rituxan for MS. Why thankfully? Because this drug kills people.
In 2009 a study from the Northwestern University Feinberg School of Medicine RADAR project, led by Charles Bennett, M.D., linked rituximab to PML.
Bennett reports on 57 cases from 1997 to 2008 in which patients with anemia, rheumatoid arthritis or lymphoma developed the fatal brain disease after taking rituximab. 90% of these patients died an average of two months after being diagnosed. The study was published in the May 14 issue of the journal Blood.
"Rituximab is one of the most prominent drugs in a new class called monoclonal antibodies. It's now the third monoclonal antibody that is associated with PML," said Bennett, the A.C. Buehler Professor in Economics and Aging at Northwestern's Feinberg School and a hematologist and oncologist at the Jesse Brown VA Medical Center in Chicago.
Bennett's RADAR project (Research on Adverse Drug Events and Reports) is an international consortium of physicians that collaborate to identify adverse reactions to medications and devices.
Bennett met with Genentech executives, offering to help them gather what thus far had been elusive information on the drug's connection to the brain infection. Doctors had been reticent to report PML in their patients who had been taking rituximab.
"It's a lot of work to produce these reports," Bennett explained about doctors' reticence.
http://www.feinberg.northwestern.edu/news/past-years/2009/2009H-May/bennett.html
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In this letter in the New England Journal of Medicine, Dr. Behan and Dr. Chaudhuri address Dr. Hauser's spectacular results(!) with rituxan in MS, and note that lesions on MRI are not related to MS progression, that the drug most likely just suppressed inflammation for awhile, as neurodegeneration continued.
http://www.nejm.org/doi/full/10.1056/NEJMc080557
To the Editor:
The monoclonal antibody described in the article by Hauser et al. is another addition to the growing list of immunotherapies that improve magnetic resonance imaging (MRI) findings and relapse rates in multiple sclerosis. Previous studies have shown that the use of antilymphocytic globulin and total lymphoid irradiation in multiple sclerosis is futile.1 In multiple sclerosis, acute demyelination can evolve without B cells,2 and one third of lesions have no lymphocytes.1 There is no disease-specific antibody in multiple sclerosis, unlike other autoimmune diseases in which rituximab is effective.
Previous lessons from trials of multiple sclerosis suggest that there is a huge gap between the treatment effect, as assessed by changes on MRI and relapse rates, and the long-term outcome, as assessed by disability measures such as the Expanded Disability Status Scale and the Multiple Sclerosis Functional Composite Scale. The gap is bridged, as in this trial, by statistical extrapolation rather than by longitudinal follow-up data. Inflammatory changes in multiple sclerosis (e.g., enhancing lesions on contrast-enhanced MRI and relapses) are probably tissue reactions to neurodegeneration rather than autoimmune in nature. The timeline of MRI changes in the rituximab trial suggests that the effect was probably antiinflammatory and not due to B-cell depletion. Unless neurodegeneration in multiple sclerosis is arrested, no form of immunotherapy, however well directed, will contain the long-term progression of disability.
Abhijit Chaudhuri, D.M., Ph.D.
Queen's Hospital, Romford RM7 0AG, United Kingdom
chaudhuria@gmail.com
Peter O. Behan, D.Sc., M.D.
University of Glasgow, Glasgow G12 8QQ, United Kingdom
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Surely, Dr. Hauser has written a mea culpa for the Annals of Neurology. Surely, he included Dr. Bennett's study in the Annals of Neurology. There must have been studies published, discussing the danger of b cell suppression and PML. Dr. Hauser must has published follow-up research on the pwMS he gave Rituxan....how were they doing, four years later? Did any develop PML or die?
So, I searched the records of the Annals of Neurology and could not find any negative studies or follow-up on Rituxan. The most recent pieces on Rituxan in the Annals of Neurology discuss
1. how darn expensive it is to create these new biologic drugs and
2. Rituximab helps those with anti–MAG demyelinating polyneuropathy.
And Dr. Hauser continues on with his b-cell research...his holy grail.
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In 2011, we see new research which illucidates how b cells may actually be protective in the mouse model of stroke. In this instance, b cells LIMIT inflammation and neurologic deficits, and these researchers recommend studying how to increase b cells. (Remember, protective autoimmunity and the debate on the function of t cells? M. Schwartz, Weizmann Institute)
http://www.jneurosci.org/content/31/23/8556.abstract
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And after all of this, the PML from depleting b cells, the failure of Rituxan in MS....Dr. Hauser is still speaking about how this is the correct path in MS research--
He was at the AAN conference this spring...
Stephen Hauser, MD, professor and chair of neurology at the University of California-San Francisco, agreed that the drugs lined up in the MS pipeline are not only giving hope but are also already “providing unique windows into the underlying biology of the disease.”
Dr. Hauser noted that the key lesion in MS is “vesiculated myelin and always with a macrophage in the vicinity.” Prior models did not truly replicate the human disease, Dr. Hauser asserted. “Clearly B cells are central players in development of focal lesions in MS.”
http://journals.lww.com/neurotodayonline/Fulltext/2011/05190/News_from_the_AAN_Annual_Meeting__A_Report_Card_on.8.aspx
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It has been very difficult to find financial conflict of interest statements on Dr. Hauser--he has made no individual disclosure statments that I can find any where online. If you do find one, please post in comments below.
But I was able to find this--
Dr. Hauser and colleagues reported final data from the double-blind, multicenter Helping to Evaluate Rituxan in Relapsing-Remitting Multiple Sclerosis (HERMES) trial.
The HERMES study was funded by Genentech and Biogen Idec.
Co-authors of the study (Hauser was the lead author) reported financial relationships with Biogen Idec, GlaxoSmithKline, Genentech, Teva Neuroscience, sanofi-aventis, AstraZeneca, Eisai Medical Research, Sanchyo Daichii, Serono, BioMS, Bayhill Therapeutics, Boehringer Ingelheim, Schering-Plough, and Genmab. Three co-authors are employees of Genentech.
http://www.medpagetoday.com/Neurology/MultipleSclerosis/8345
Dr. Hauser serves as Member of Scientific Advisory Board of Rinat Neuroscience Corporation. Dr. Hauser serves as Member of the Clinical Advisory Board at Receptos, Inc. He serves as Member of Scientific Advisory Board at BioMarin Pharmaceutical Inc.
http://investing.businessweek.com/research/stocks/people/person.asp?personId=27851489&ticker=BMRN:US&previousCapId=22555&previousTitle=Prospect%20Venture%20Partners
There is a tremendous conflict of interest at this journal. There is tremendous hypocrisy. A perfect storm....
Joan
