Good News! A new multicenter clinical trial is or will soon be recruiting RRMS patients at various locations across the US and UK.

Details at link.

https://www.prnewswire.com/news-releases/clinical-trial-of-autologous-hematopoietic-stem-cell-transplantation-versus-best-available-therapy-for-multiple-sclerosis-beat-ms-begins-enrollment-300982428.html

Center locations and contact information are as follows.

United States, California
Stanford Multiple Sclerosis Center Not yet recruiting
Palo Alto, California, United States, 94304
Contact: Yamuna Joseph    650-529-5524    yamuna@stanford.edu
Principal Investigator: Jeffrey Dunn, MD, FAAN
       
United States, Colorado
Rocky Mountain Multiple Sclerosis Center, University of Colorado School of Medicine Not yet recruiting
Aurora, Colorado, United States, 80045
Contact: Haley Steinert    303-724-4172    Haley.Steinert@ucdenver.edu 
Principal Investigator: John R. Corboy, MD
       
United States, Massachusetts
Multiple Sclerosis Center, University of Massachusetts Memorial Medical Center Not yet recruiting
Worcester, Massachusetts, United States, 01605
Principal Investigator: Carolina Ionete, MD, PhD
       
United States, Minnesota
University of Minnesota Multiple Sclerosis Center Not yet recruiting
Minneapolis, Minnesota, United States, 55455
Contact: Susan Rolandelli    612-624-8431    rolan010@umn.edu 
Principal Investigator: Flavia Nelson, MD
       
Neurology, Mayo Clinic Not yet recruiting
Rochester, Minnesota, United States, 55905
Contact: Sandra Looney    507-538-4107    Looney.Sandra@mayo.edu 
Principal Investigator: B. Mark Keegan, MD,FRCPC
       
United States, Missouri
John L. Trotter Multiple Sclerosis Center, Washington University School of Medicine in St. Louis Not yet recruiting
Saint Louis, Missouri, United States, 63110
Contact: Susan Sommer    314-362-2017    foxs@wustl.edu 
Principal Investigator: Gregory Wu, MD, PhD
       
United States, New York
Baird Multiple Sclerosis (MS) Center, Kaleida Health Not yet recruiting
Buffalo, New York, United States, 14203
Contact: Kara Patrick    716-829-5037    kpatrick@buffalo.edu 
Principal Investigator: Bianca Weinstock-Guttman, PI       
Corinne Goldsmith Dickinson

Center for Multiple Sclerosis at Mount Siinai  Not yet recruiting
New York, New York, United States, 10029
Contact: Elise Digga    212-241-3391    elise.digga@mssm.edu 
Principal Investigator: Aaron Miller, MD
       
Rochester Multiple Sclerosis Center, University of Rochester Not yet recruiting
Rochester, New York, United States, 14620
Contact: Patti Fenton, RN    585-275-6120     
Principal Investigator: Andrew D. Goodman, MD
       
United States, North Carolina
Neurology, Duke University Medical Center Not yet recruiting
Durham, North Carolina, United States, 27710

United States, Ohio
University of Cincinnati (UC) Waddell Center for Multiple Sclerosis Not yet recruiting
Cincinnati, Ohio, United States, 45219
Contact: Ameneh Zare    513-558-0105    zareshae@ucmail.uc.edu 
Principal Investigator: Aram Zabeti, MD
       
Mellen Center for Multiple Sclerosis Treatment and Research, Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Tim Hudec    216-445-1450    hudect@ccf.org 
Principal Investigator: Jeffrey A. Cohen, MD
       
United States, Oregon
Multiple Sclerosis Center, Oregon Health & Science University Not yet recruiting
Portland, Oregon, United States, 97239
Contact: Debbie Guess, RN    503-494-7651    griffide@ohsu.edu 
Principal Investigator: Yadav Vijayshree, MD,MCR,FANA,FAAN
       
United States, Pennsylvania
Penn Comprehensive MS Center, Hospital of the University of Pennsylvania Not yet recruiting
Philadelphia, Pennsylvania, United States, 19104
Contact: Tanyra Smith    215-662-4893    tanyra.smith@uphs.upenn.edu 
Principal Investigator: Amit Bar-Or, MD,FRCP,FAAN,FANA
       
United States, Texas
University of Texas Southwestern Medical Center: Division of Multiple Sclerosis and Neuroimmunology Not yet recruiting
Dallas, Texas, United States, 75390
Contact: Jan Cameron-Watts    214-645-0563    jan.CameronWatts@UTSouthwestern.edu 
Principal Investigator: Benjamin Greenberg, MD
       
Maxine Mesigner Multiple Sclerosis Comprehensive Care Center, Baylor College of Medicine Medical Center Not yet recruiting
Houston, Texas, United States, 77030
Contact: Tahari Griffin    713-798-6097    tgriffin@bcm.edu 
Principal Investigator: George J. Hutton, MD
       
United States, Virginia
Virginia Commonwealth University Multiple Sclerosis Treatment and Research Center Not yet recruiting
Richmond, Virginia, United States, 23219
Contact: Jeneane Henry, RN,BSN    804-828-7802    jeneane.henry@vcuhealth.org 
Principal Investigator: Unsong Oh, MD
       
United States, Washington
Clinical Research Division, Fred Hutchinson Cancer Research Center Not yet recruiting
Seattle, Washington, United States, 98109
Contact: Bernadette McLaughlin    206-667-4916    bmclaugh@fredhutch.org 
Principal Investigator: George E. Georges, MD
       
Multiple Sclerosis Center, Swedish Neuroscience Institute Not yet recruiting
Seattle, Washington, United States, 98122
Contact: Bernadette McLaughlin    206-667-4916    bmclaugh@fredhutch.org 
Principal Investigator: James D. Bowen, MD
       
Multiple Sclerosis Center at Northwest Hospital Not yet recruiting
Seattle, Washington, United States, 98133
Contact: Elisa McGee       emcgee@uw.edu 
Principal Investigator: Annette Wundes, MD
       
United Kingdom
Imperial College Healthcare NHS Trust Not yet recruiting
London, United Kingdom, W12 0NN
Principal Investigator: Paolo A. Muraro, MD,PhD

HSCT for MS New Results Published in JAMA

Great news! Recent HSCT results published in JAMA continue to show the procedure is very effective at halting MS autoimmune disease. In fact, it's much better than standard of care disease-modifying drugs. 

As reported in CNN today :

“...the proportion of patients with no evidence of disease -- defined as no progression, no relapses, and no new or enlarging lesions on MRI scans -- was (nearly) 98% at one year, 93% at two years, 90% at three years, and 78% at four and five years.”

As for me, personally, I received HSCT treatment five years ago this month. MRI scans continue to show that my autoimmune MS continues to be halted without the use of disease modifying MS drugs. THANK YOU DR. BURT!

HSCT for MS -- Insurance Battles Continue

I can relate to this article. It's now one year after my HSCT treatment in Chicago. Blue Cross Blue Shield Minnesota refused to pay after four appeals, so I had to self pay in order to get treated at Northwestern, stop my MS and stop taking expensive MS drugs and plasmapheresis treatments that had horrible side effects and didn't work. In addition to giving me another shot at life and keeping me off disability, HSCT is saving BCBS approximately $150,000 a year.

My case against BCBS is now in the hands of a federal judge. It boggles my mind that they are fighting me on this. My lawyer, who is working on contingency, thinks we have a strong case. We'll see.

http://fox17online.com/2015/02/09/doctor-calls-life-changing-stem-cell-treatment-a-win-win-for-patients-and-insurance-companies/

Doctor calls life-changing stem cell treatment a ‘win-win’ for patients and insurance companies

POSTED 10:39 PM, FEBRUARY 9, 2015, BY JESSICA MCMASTER, UPDATED AT 09:51PM, FEBRUARY 10, 2015

CHICAGO, Ill.– A doctor who performs stem cell transplants for people with debilitating diseases calls the procedure a “win-win” for both the patient and their insurance provider.

For the past 30 years, Dr. Richard Burt with Northwestern Memorial Hospital in Chicago, has been researching stem cell transplants.

“We certainly are seeing results that nobody else has seen before,” Dr. Burt said. “We had people that have gone to major medical centers around the country and it’s just more of the same. They continued to decline and they come to us and get a transplant and they get off all therapy and they just get better and better.”

Cory Smallegan, from Grand Rapids, said he was one of Dr. Burt’s patients.  He says that he’s been given a second chance at life due to the transplant.

“A month or so later, I was running and climbing up stairs and doing all sorts of things I couldn’t do before,” Smallegan said.

Smallegan was diagnosed with chronic inflammatory demyelinating polyneuropathy in 2011.  It’s a rare neurological disorder that causes progressive weakness in the arms and legs. Prior to the transplant, he said he was making arrangement to live his life from a wheelchair.

“My legs just couldn’t lift up. Normal people can stand on their toes, I couldn’t do that,” Smallegan said. “I would fall…I would run into things.”

Lori Mills was also diagnosed with CIDP. She’s in the process of seeing Dr. Burt for treatment.

“I got to the point where I was paralyzed–couldn’t move at all,” she said.

In order to get the transplant, a patient first needs to have their diagnoses confirmed by Dr. Burt. He then gives them a one-time treatment that nearly wipes out their immune system. They’re then infused with their own stem cells, which rapidly regenerates a new immune system that functions how it’s suppose to.

“We’re able to reverse disability,” Dr. Burt said.

The only problem is, health insurance providers don’t always cover the procedure. While Blue Cross Blue Shield has agreed to cover Mills’ transplant, Smallegan is now more than $125,000 in debt because BCBS denied him coverage, stating the transplant was a “clinical trial.”

Without the treatment, Mills and Smallegan said they’d both be on IVIg treatments and steroids for the remainder of their lives. Not only do they say those treatments did little to make them better, they said it was expensive, costing BCBS nearly $40,000 a month.

Smallegan, who’s no longer on any treatments, said he’s saved BCBS big money.

“Blue Cross has now saved $1.2 million alone not paying for my treatments,” he said.

Dr. Burt told FOX 17 that getting insurance to cover the procedure is a process. That the medical effectiveness of the treatment has to be proved through published data, which he’s working on. In the meantime, he said stem cell transplants are helping countless patients with various diseases, such as, multiple sclerosis and crohn’s disease.

“I have no doubt that it’s a win-win. It’s a win for the insurance company because it saves money capered to continuing IVIg or plasma feresis,” Dr. Burt said. “It’s a win for the patient because they don’t have to have all these other therapies and they get better.”

FOX 17 reached out to Blue Cross Blue Shield to learn why some patients are covered when it comes to the procedure when other’s are not. They haven’t returned the calls and emails by Monday.

Mills is going through the process of having the stem cell transplant.

“I’ll get that shot again,” she said. “I’m just excited at the whole new shot at life.”

Hunt for an MS Cure? Newsweek Missed the HSCT News

Newsweek's February 4, 2015 article The Hunt for a Multiple Sclerosis Cure, is ambitious in scope and, for a popular audience, is deftly written. It's worth a read, with some insights about the human suffering caused by MS interspersed with a smattering of interesting research into possible future cures.

The problem with an article like this is that it's bound to miss a lot. And in this case, missing HSCT was a huge miss! I did HSCT at Northwestern University in Chicago one year ago. It stopped my very aggressive RRMS. I no longer need MS drugs. A recent JAMA paper by Dr. Richard Burt summarizes the success of the procedure so far with 151 patients. Most patients improved by at least one point on the disability scale and nearly 85% showed no evidence of further MS disease activity after two years. No other drug or procedure comes as close to being a cure!  See Dr. Burt's report here.
http://www.stemcell-immunotherapy.com/article_pdfs/jama-jan-20-2015-vol-212-number-3.pdf

ALERT: Northwestern is still recruiting patients for a Phase 3 study Stem Cell Therapy for Patients With Multiple Sclerosis Failing Alternate Approved Therapy - A Randomized Study
https://www.clinicaltrials.gov/ct2/show/NCT00273364?term=failing+beta+interferon&rank=2

Acorda's Remyelinating Antibody -- The MS Drug Trial I Missed

The holy grail for MS treatment is finding a drug that rebuilds the protective myelin sheath around nerves.

In 2012, I had been called to be a test subject in a Phase 1 safety and tolerability study for a remyelinating drug from Acorda that had shown promise in mice. My spinal cord had spots where my immune system had damaged the myelin. My wiring was literally shorting out, leg control was starting to fade, and I was more than ready to be one of the first humans tested on the drug.

But then a very severe MS attack hit me and I was disqualified from the study. I was devastated when Acorda proceeded without me.

But I was later fortunate to be accepted for Dr. Burt's different stem cell transplant (HSCT) study a few months later.

All's well that ends well. HSCT stopped my MS attacks, so my nerves can now slowly heal naturally. And nobody died in the Acorda study. It now appears that the Acorda drug is safe enough to move on to Phase 2. This is great news for future MS patients, and perhaps victims of spinal cord injury. But bear in mind that FDA studies take a long time. If the Acorda drug passes the next rounds of testing, it will still be at least a decade before it's approved for the marketplace.

The Phase I study results are still being tabulated. One February 6, 2015 the study is listed as active but not recruiting.  Stay tuned . Acorda could start recruiting for Phase 2 at any time.

https://www.clinicaltrials.gov/ct2/show/NCT01803867?term=acorda&rank=21

http://multiplesclerosisnewstoday.com/2015/02/06/acorda-announces-phase-1-results-for-remyelinating-antibody-in-multiple-sclerosis/

    

HSCT for MS Risky But Effective

Several research centers around the world are starting to release early-stage data on the efficacy and safety of using HSCT to treat MS. Their procedures are all similar, but a bit different in their intensity when compared to what Dr. Burt did for me in Chicago. The article pasted below is a summary with quotes from different HSCT doctors, including Dr. Burt.  It's a good read, and surprisingly balanced considering that the website that posted it is sponsored by MS drug companies. I do like the mouse with   a hammer cartoon that goes with it.

Today is my birthday. It's a  bonus year. Exactly one year ago, I was in a chemo ward at Chicago Northwestern University. I was getting my immune system reset to stop a very aggressive form of MS. The path that had led me to that place was painful, terrifying and enraging. Despite using powerful MS drugs (and perhaps partly because of them, considering what doctors are still learning about Tysabri rebound) an autoimmune attack had scarred my brainstem, crippled and almost killed me.

Months before, I remember sitting in a wheelchair across from Dr. Burt and hoping desperately that he would treat me with his HSCT procedure. After shaking my hand, his first words were: "You know this procedure could kill you, right?"

I said yes, I'd read all the studies and was well aware of the danger. Based on limited data, it looked like mortality with HSCT was one in 100, more or less. But effectiveness at stopping the disease appeared to be 80%. Doctors weren't calling HSCT a cure, but a growing number of patients were. I liked those odds.

Besides all that, I was out of acceptable options. The prominent Minneapolis neurologist who had been treating me unsuccessfully was obviously floundering with my case, moving me from Betaseron, to Tysabri, to Tecfidera, with lots of steroids in between.  Drug companies were making a fortune, but I wasn't being helped.

Seven years of MS drugs, and I was deteriorating. Over the years, I'd also noted the condition of the other patients in the neurologist's waiting room. The ones I remembered seemed to be getting worse, too. I learned that a couple of my fellow MSers had died. The neurologist looked exhausted. He was scrambling from one crisis to the next. I started to view his MS clinic as a hospice service. I think that's how he often viewed it too.

For me, it was past time for a change. If I kept getting worse, nerve damage would pass the point of no return. I was more than willing to go down fighting if there was reasonable chance HSCT would stop the MS and get me off the drugs. So I ignored the neurologist's dire warnings about the dangers of HSCT and moved ahead to be treated by Dr. Burt.

In February, I will go back to Chicago for my one-year evaluation and MRI. My six-month evaluation showed no evidence of disease activity and no complications.  I expect the one-year MRI to show positive news as well. But I'm not taking anything for granted. The data for me, and everyone else, is still being collected.

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http://www.msdiscovery.org/news/new_findings/16252-stem-cell-transplants-risky-effective

Stem Cell Transplants Risky But Effective

Initial results from the HALT-MS trial suggest that autologous hematopoietic stem cell transplantation may be a highly effective treatment for patients with aggressive relapsing-remitting MS. However, some worry that the aggressive therapy is needlessly risky when safer alternatives are available and may be just as effective.

CYNTHIA MCKELVEY

Cartoon by Cynthia McKelvey.

It appears that a complex series of genetic and environmental factors pile on top of each other over the course of an individual’s life to trigger multiple sclerosis. Wouldn’t it be great if patients could just hit the “reset” button on their immune system and start again with a clean slate? Results from the HALT-MS clinical trial suggest that idea may be more realistic than it sounds.

Three years ago, 24 patients with highly aggressive relapsing-remitting MS (RRMS) underwent autologous hematopoietic cell transplants (HCT)—a risky procedure that involves harvesting a patient’s hematopoietic stem cells from their bone marrow, destroying almost all of the immune system, and then replacing it with the undifferentiated stem cells. The phase 2 trial has so far had excellent results, with most of the patients showing no signs of disease activity.

But not everyone is popping the champagne just yet. While hematopoietic stem cell transplants could theoretically be a one-time treatment that could lead to lifetime remission from MS, only time will tell if the treatment is that durable. And some skeptics aren’t holding their breath.

The study

The HALT-MS results reported in JAMA Neurology represent the three-year interim report (Nash et al., 2014). The final report will come out in 2 years.

The researchers defined the primary outcome measure as “event-free survival defined as survival without death or disease activity from any one of the following outcomes: (1) confirmed loss of neurologic function, (2) clinical relapse, or (3) new lesions observed on magnetic resonance imaging.” This type of outcome measure is increasingly being referred to as “no evidence of disease activity,” or NEDA, though it’s unclear how feasible of a long-term goal it may be.

Nevertheless, 78.4% of the study participants achieved NEDA at 3 years, compared to 39% of patients receiving alemtuzumab at the 2-year follow-up in the CARE MS1 trial (Rotstein et al., 2014).

“It’s dramatically higher efficacy,” Michael Racke, M.D., of Ohio State University told MSDF. Racke, who was one of the study’s co-authors, pointed out that it could be a potentially cheaper treatment option as well, presuming the effects are long-lasting and patients would only need to undergo the procedure once.

Of course one limitation of the study is a lack of a control group. And with such an intense treatment, there is bound to be a placebo effect, James Bowen, M.D., of the Swedish Neuroscience Institute in Seattle, WA, who was also involved in the study, told MSDF.

“It’s a reason to do MRIs and it’s also a reason to do a 5-year follow-up. Five years gives us more time for that placebo effect to wear off,” Bowen said.

When asked how the treatment works, Racke told MSDF, “Theoretically, if you look at identical twins where one twin has MS, 75% of the time the other twin doesn’t have MS. What we’re trying to do is make an MS patient their own identical twin that doesn’t have MS.”

But what does that mean, exactly?

How it works

To perform HCT, physicians must first harvest undifferentiated hematopoietic stem cells from the patient’s bone marrow. Then the patient undergoes a conditioning regimen that uses chemotherapy and radiation to destroy part or almost all of their immune system. These conditioning regimens can be myeloablative or nonmyeloablative; they can eradicate the bone marrow or not. Myeloablative regimens, like the one used in the HALT-MS trial, are more conventional but also riskier and more intense.

After the conditioning regimen, assuming no adverse events such as infections occur, the patient’s stem cells are grafted back into the body, where they differentiate and rebuild the immune system from the ground up. Of course, the question remains whether autoreactive cells would reappear, causing a relapse.

“I’m a neurologist, so all of these therapies are pretty aggressive from a neurology perspective. I was thinking ‘Oh we’re just going to kill off your entire immune system and replace it,’ ” Bowen said. But it’s more complicated than that; the immune system doesn’t replace itself so much as it redevelops, similar to how it does in embryogenesis.

“When an immune system is developing during embryogenesis it goes through a stage where it deletes autoclones—you delete the bad guys that are able to attack your own body,” Bowen said. “But when you’re transplant people, [the immune system] goes through this stage where it deletes autoclones.”

The transplant also causes certain shifts in cell populations, such as CD4 and CD8 cells. “In addition to kind of changing out of the immune system, you also get this shift in the immune system in a way that we think is less likely to be autoimmune,” Bowen said.

But is it really necessary to obliterate a patient’s immune system to accomplish this? Not everyone agrees.

Dialing in the intensity

HCT is more often used in aggressive cancers such as leukemia. These patients would almost certainly die without treatment, so physicians are more willing to take risks. But MS is not considered to be a terminal illness, calling into question the optimal way to balance risk with reward.

Conventional wisdom says that in order to get a true immunological reset, one must remove all traces of the dysfunctional immune system before transplanting the stem cells. The thinking is that autoreactive immunological cells that survive could easily multiply and continue to attack the immune system.

“The whole point of doing this is to wipe out the disease-causing cells,” Mark Freedman, HBSc, MSc, MD, CSPQ, FAAN, FRCPC, of the Ottawa Hospital Research Institute told MSDF. “If you can’t wipe them out completely, then what’s the point of subjecting people to this terrible procedure which can kill people?” Freedman was not involved in the study but is conducting his own HCT trial using a more intense conditioning regimen than the one used in HALT-MS.

Freedman believes it’s necessary to wipe out every last disease-causing cell, which would require risking the patient’s overall health since the conditioning regimen is nonspecific and will kill the “good guys” along with the “bad guys.” He told MSDF he believes that the regimen in HALT-MS was not intense enough, which would explain why only 78.4% of the patients are showing no sign of disease activity instead of 100%.

“It’s a matter of time before other individuals have reactivation of their disease, and it’s probably because they didn’t knock out all the cells,” Freedman said.

But such aggressive treatments may come with a hefty price. While they may work in the short term, the chemotherapy will increase the risk of cancer in the long term, and opinions are varied on whether it’s worth it. While some researchers, such as Freedman, believe that the conditioning regimen in HALT-MS was not intense enough, others believe that it was too intense.

“Autoreactive cells are normal. Cells that recognize cells are normal. But the disease is pathologic,” Richard Burt, M.D., of Northwestern University told MSDF. In other words, there are no good guys or bad guys, so the goal should not be to totally eradicate the bad guys but to change the interaction between the cells. Burt believes that the intense regimens used on cancer patients and in the HALT-MS trial are dangerous and unnecessary for patients with MS (Burt et al., 2010). Instead, he and his team use a nonmyeloablative conditioning regimen. They will be publishing results from their trials later this month.

“What you want to do is knock your immune system down sufficiently, but you don’t want to get rid of every last one. You want to stop inflammation,” Burt said.

Immune cells react to a number of stimuli, Burt said, and sometimes the cells become confused by stimuli and attack the body, leading to autoimmunity. But if the noise of the stimuli can be removed, then the immune cells can learn tolerance and not attack the body. Burt said removing inflammation, which can be achieved by his nonmyeloablative procedure, is the key to reprogramming the immune system.

Nonetheless, physicians who perform stem cell transplants continue to improve their techniques, ultimately reducing the morbidity and mortality rates resulting from the conditioning regimen (Soldán and Weinshenker, 2014). MS patients also tend to be healthy in every regard except for their disease, and thus seem likely to tolerate the regimens better than cancer patients. But the jury is still out on the ideal risk-benefit ratio for conditioning MS patients.

The gift that keeps on giving

Some evidence also suggests that the stem cells may lead to neuroregeneration, though the researchers were unable to track that outcome in the HALT-MS trial. In animal studies, HCT seems to lead to a restoration of nerve function, Freedman said.

But it’s difficult to monitor restoration in humans. “The problem is in the face of ongoing activity or damage, it’s very hard to see any kind of repair,” Freedman said. “[It’s] like you’re now the road crew who’s going to go out in a country where the war’s going on and you’re fixing the roads. Hopefully the bombs aren’t going off.”

The conditioning regimen, followed by the HCT, may be enough to stop the bombs, he added.

At the end of his interview with MSDF, Bowen emphasized that this sort of treatment is a last-ditch effort reserved only for patients whose RRMS is very aggressive and unresponsive to conventional treatments. But for some patients, that may leave a very narrow window of opportunity.

The line between relapsing-remitting and secondary progressive MS (SPMS) is blurry, but it’s important to define that line when deciding on stem cell therapy. Since progressive forms of MS are considered neurodegenerative, not inflammatory, stem cell transplantation is highly unlikely to have any meaningful effect on SPMS patients. While it’s always difficult to determine when a patient crosses the line from relapsing to progressive MS, patients with particularly aggressive forms of RRMS can be especially hard to treat, Freedman said.

“What you don’t want to do is go down a shopping list of 10 to 12 drugs, meanwhile the patient has now advanced to a stage where a bone marrow transplant won’t do them any good,” Freedman said. “You’re dealing with a war.”

Key open questions

• What is the best conditioning regimen for patients with MS?
• How can physicians best intervene before patients slip into the progressive phase of the disease?
• What other ways might HCT be made safer and more effective?
• How long will the effects of HCT be sustained in MS patients?

Disclosures and sources of funding

This work was sponsored by the Division of Allergy, Immunology and Transplantation, National Institute of Allergy and Infectious Diseases. Baxter Healthcare Corporation supplied some equipment and reagents without charge.

Racke received grants from the National Multiple Sclerosis Society and Teva and was a consultant for Biogen Idec, Novartis, Questcor, and Revalesio.

Bowen receives grants from NIH/NIAID; personal fees from Pfizer and Teva Neuroscience; personal fees and research contracts from Biogen, EMD Serono, and Novartis; and research contracts from Genentech, Genzyme, GlaxoSmithKline, Medimmune, and Sanofi-Aventis.

Freedman and Burt reported no conflicts of interest

More Clues to Why HSCT Works to Stop MS

Last January in Chicago I was waiting for my stem cells to engraft and give me a new self-tolerant immune system.  It was a time of isolation to avoid infection, so there was little for me to do but  survive, meditate and read.

One of the things that tripped across my news feed then was an HSCT MS study in Canada that seemed very similar to Dr. Burt's procedure.  I asked Dr. Burt about it when he stopped by on his daily rounds to visit me. He said the Canadian study was a similar procedure, but that he believed the chemo being used there was unnecessarily harsh. The Canadian study, managed by Dr. Mark Freedman, was an early-stage effort with only 24 patients.  Dr. Burt's ongoing Phase 3 study will enroll hundreds of patients.

A March 2013 Science Daily article summarized some of the results of that Canadian study. These appear to support Dr. Burt's hypothesis about how HSCT resets the immune system back to a balanced, self-tolerant state. The article, posted below, talks about a lasting reduction of Th17 immune cells. (An overabundance of Th17 cells appears to set off a chain reaction of other immune cells that begin attacking the central nervous system.)

Anyway, it's reassuring to have more confirmation that HSCT works to stop MS, and also about how and why it works at the molecular level. I certainly don't understand it all, but it amazes me that scientists are not only figuring out the complex workings of the human immune system, but also finding ways to fix it when it's broken, like mine was.

And, having done HSCT myself, I have a different perspective on the concept of "risky" as stated in the article below.  Risky compared to what? A life in a wheelchair while taking poorly understood immune-modulating drugs with their own risks and side effects?  I'm so glad I did HSCT, and grateful that Dr. Burt's experience with the procedure, along with his professional team of nurses and specialists at Northwestern Memorial Hospital, minimized that risk significantly.

Best wishes and good luck to my new friends and acquaintances who are preparing to undergo the HSCT procedure in Chicago and elsewhere in the world! And especially good wishes to all those suffering from MS and other autoimmune diseases who are still in "wait and see" mode in regard to HSCT.  Science keeps learning more as Dr. Burt's Phase 3 study continues.  Dr. Burt's Phase 1 and 2 results continue to be very positive, with lasting results for most treated patients who remain in remission years later. The early stage Canadian study posted below also looks positive for HSCT.

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Major advance in understanding risky but effective multiple sclerosis treatment

Date:

March 26, 2013

Source:

McGill University

Summary:

A new study by multiple sclerosis researchers addresses why bone marrow transplantation has positive results in patients with particularly aggressive forms of MS.

new study by multiple sclerosis researchers at three  Canadian centres addresses why bone marrow transplantation (BMT) has positive results in patients with particularly aggressive forms of MS. The transplantation treatment, which is performed as part of a clinical trial and carries potentially serious risks, virtually stops all new relapsing activity as observed upon clinical examination and brain MRI scans. The study reveals how the immune system changes as a result of the transplantation. Specifically, a sub-set of T cells in the immune system known as Th17 cells, have a substantially diminished function following the treatment.

Related Articles

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• Bone marrow transplant
• Bone marrow
• Multiple sclerosis
• Stem cell
• Bone scan
• Leukemia

The finding to be published in the upcoming issue ofAnnals of Neurology and currently in the early online version, provides important insight into how and why BMT treatment works as well as how relapses may develop in MS.

"Our study examined why patients essentially stop having relapses and new brain lesions after the bone marrow transplant treatment, which involves ablative chemotherapy followed by stem cell transplantation using the patient's own cells," said Prof. Amit Bar-Or, the principle investigator of the study, who is a neurologist and MS researcher at The Montreal Neurological Institute and Hospital -The Neuro, McGill University, and Director of The Neuro's Experimental Therapeutics Program. "We discovered differences between the immune responses of these patients before and after treatment, which point to a particular type of immune response as the potential perpetrator of relapses in MS."

"Although the immune system that re-emerges in these patients from their stem cells is generally intact, we identified a selectively diminished capacity of their Th17 immune responses following therapy -- which could explain the lack of new MS disease activity. In untreated patients, these Th17 cells may be particularly important in breaching the blood-brain-barrier, which normally protects the central nervous system. This interaction of Th17 cells with the blood-brain barrier can facilitate subsequent invasion of other immune cells such as Th1 cells, which are thought to also contribute to brain cell injury.

Twenty-four patients participated in the overall clinical trial as part of the 'Canadian MS BMT' clinical trial, coordinated by Drs. Mark Freedman and Harry Atkins at the Ottawa General Hospital. The new discovery, made in a subset of patients participating in the clinical trial, was based on immunological studies carried out jointly in laboratories at The Neuro and the Université de Montréal. Results of this study not only show the clinical benefits of BMT treatment, but also open a unique window into the immunological mechanisms underlying relapses in MS. Th17 cells could be the immune cells associated with the initiation of new relapsing disease activity in this group of patients with aggressive MS. This finding deepens our understanding of MS and could guide the development of personalized medicine with a more favourable risk/benefit profile.

Among the patients treated in the Canadian MS BMT clinical trial, was Dr. Alexander Normandin, a family doctor, who was a third- year McGill medical student getting ready for his surgery exams when he first learned he had MS, "I was so engrossed in my studies that I didn't pay attention to the first sign but within a few days of waking up with a numb temple, my face felt frozen. I learned that I had a very aggressive form of MS and would probably be in a wheelchair within a year. It was a brutal blow. I became patient #19 -- of only 24 for this experimental treatment. My immune system was knocked out and then rebooted with my stem cells. Today, my MS has stabilized. I now have this disease under control and I take it one day at a time."

Both the clinical and biological studies were supported by the Research Foundation of the Multiple Sclerosis Society of Canada.

Multiple Sclerosis

MS is a disorder of the brain and spinal cord that causes fatigue, disequilibrium, sensory problems and muscle paralysis. The cause of MS is unknown, but evidence suggests that it is an auto-immune disease that destroys myelin, a substance coating axons, the thin strands that carry signals between brain cells.It usually strikes between the ages of 15 and 40 but can begin as early as age two. Women have twice the probability of developing MS than men. Canada has one of the world's highest national rates -- about 1,100 new cases each year. Some 50,000 Canadians have MS. More than 1 in 5 lives in Quebec. The most common form of MS is relapsing-remitting, in which acute symptoms alternate with periods of remission. Primary progressive MS, the least common form, develops continually without remission. Secondary progressive MS begins as relapsing-remitting, then becomes steadily progressive.

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Story Source:

The above story is based on materials provided by McGill University. Note: Materials may be edited for content and length.

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Journal Reference:

1. Peter J. Darlington, Tarik Touil, Jean-Sebastien Doucet, Denis Gaucher, Joumana Zeidan, Dominique Gauchat, Rachel Corsini, Ho Jin Kim, Martin Duddy, Farzaneh Jalili, Nathalie Arbour, Hania Kebir, Jacqueline Chen, Douglas L. Arnold, Marjorie Bowman, Jack Antel, Alexandre Prat, Mark S. Freedman, Harold Atkins, Rafick Sekaly, Remi Cheynier, Amit Bar-Or. Diminished Th17 (not Th1) responses underlie multiple sclerosis disease abrogation after hematopoietic stem cell transplantation. Annals of Neurology, 2013; DOI: 10.1002/ana.23784