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

Adverse Drug Events with Tysabri

Before HSCT stopped my MS, I was failed by the drug Tysabri. This week I received a letter in the mail from the MS neurologist I no longer see. He wants to include my medical data as part of "a multi-center, retrospective, observational study evaluating real-world clinical outcomes in relapsing-remitting multiple sclerosis patients who transition from Tysabri (natalizumab) to Tecfidera (demethyl fumarate)."

Since doing HSCT with Dr. Burt, I no longer need MS drugs or my old neurologist anymore. But I am giving permission to use my old Tysabri data. I understand most MS patients don't yet have the opportunity I had to do HSCT. Patients and their doctors will need the best information possible for their drug decisions. I sincerely hope the study can help prevent other patients from experiencing the kind of botched treatment that crippled me with a horrific Tysabri rebound attack. I'm still rehabbing my ability to walk normally as the damaged nerves slowly heal.

I also hope the study isn't used out of context in order to promote Tysabri as the most effective treatment for MS. As new information is revealed, evidence is building that though Tysabri has some powerful activity against MS, it's buying time at best, or a deal with the devil of adverse drug events at worst.

Adverse Events 
Other than a few hundred people who have died specifically from the rare brain infection PML, brought on Tysabri use, we're left to guess about other adverse events with Tysabri. A new online data mining application shows 97,873 adverse events with Tysabri since 2005. (ADDENDUM: AS OF DECEMBER 30, 2014, THE NUMBER OF REPORTED ADVERSE EVENTS WITH TYSABRI HAS INCREASED TO 109,447.) My personal adverse event with the drug was severe, but is likely not included among the thousands in the database. I have no idea how many unreported others there are like me.  This chart shows those that have been reported.

As many thousands of patients continue to be infused with Tysabri around the world, researchers are still trying to figure out how it works at the molecular level. I'm no doctor or immunologist; the components of the human immune system are Greek to me. But the more I learn, the more it seems most doctors, particularly drug-prescribing neurologists, really don't know how the immune system works either. From research papers I find online, the best I can figure is that B cells and T cells of the immune system become imbalanced on Tysabri, which offers an uncertain mix of benefits and risks while treating MS.

Perhaps the most telling thing is that Lawrence Steinman, the Stanford immunology researcher  who invented Tysabri, says that the benefits of Tysabri are not worth the risk. He advises patients and doctors to consider other treatment options. I wish I'd known about Dr. Steinman before I'd trusted my neurologist when he told me Tysabri risk was manageable.

Nerve Damage Recovery After MS

"Healing is a matter of time, but it is sometimes also a matter of opportunity."
– Hippocrates, 400 BC


HSCT Worked!
HSCT did what it was supposed to do for me. Eight months ago it reset my immune system and stopped my MS. It was a rare opportunity and what some might consider an extreme measure to heal myself with modern technology. My only regret is that I didn't do HSCT sooner. My health has been phenomenally good since getting a new immune system that no longer attacks me. Without living in a bubble, I've avoided any serious infections or illnesses. It feels great being off MS drugs. No more needles or nasty drug side-effects! When I look at myself, I do not see someone who has MS. For me, MS is over.

But… My nerves and mobility are not 100 percent recovered. While most of the MS symptoms have abated, I still walk poorly and my fingers aren't coordinated enough to play guitar. Nerve damage from MS heals slowly. For now, I'm very grateful to be able to type, hold a dinner fork, drive my car, and walk a few blocks. Healing improvements are happening, but slowly.

Miracles Happen Slowly
The bone marrow stem cells used in HSCT reset the immune system and stop the autoimmune attacks, but they don't heal nerves. If my recovery pattern follows that of the few hundred trailblazing HSCT MS patients before me, Dr. Burt says natural nerve healing and improvements will likely keep happening for three years. With the autoimmune attacks halted, nerves can remyelinate and heal. My body can also find new nerve pathways. Burt's advice is to drink plenty of water, eat a normal healthy diet and do physical therapy.

HSCT is no shortcut. Dr. Burt's research has spanned 30 years, with at least 10 more years to go. The stakes are much higher than just one patient. He's following painstaking research protocols with his Phase III study to give HSCT the best chance of receiving FDA approval for treating many thousands of autoimmune patients in the future.

My Recovery 
Meanwhile, there's no shortcut for me, either. I get impatient, wanting to charge ahead to do whatever it takes to walk normally again. Maddeningly, I have to go slow, can't do it alone, and need help. Fortunately, just as I found Dr. Burt, I've also found and assembled my own personal rehab team. Kim, Mike and Matt are amazing. My training regime and rehab team is as follows:

Walking (with and without a cane, as much as possible)

Daily Stretching and Yoga (at home)

Daily Stair Climb (up and down nine floors)

Pilates Twice a Week (Kim Taraschi at New Movement Pilates)

Physical Therapy (Mike Fricke at Pro Physical Therapy Muskoskeletal Balancing)

Acupuncture Twice a Week (Matt Bierschbach at Acupuncture Center of Minneapolis)



Victory is won not in miles but in inches. Win a little now, hold your ground, and later, win a little more. 
– Louis L'Amour 

Good Results with HSCT

Thanks to everyone who has been so supportive of me during my past difficult years fighting (and beating!) MS. I can't begin to list everyone. Just please know you are appreciated. I'm healthy and learning to walk again. The cane I carry is mostly for menacing feral cats, small dogs and naughty children who might get in my way. 

Since HSCT, my walking has improved and the wheelchair goes unused. No more MS drugs for me! I currently do Pilates and PT to rehab my gimpy gait. Eight months after treatment, it appears I am one of the HSCT success stories. At some point soon, I hope to get rid of the cane entirely. 

Of the hundred or so HSCT patients who were treated before me, the results are promising. The following paper came out the year prior to me doing HSCT with Dr. Burt in Chicago. It's one of the best summaries I've read.

The development of hematopoietic and mesenchymal stem cell transplantation as an effective treatment for multiple sclerosis

...Progression-free survival after HSCT, measured by neurological improvement, decreased disability, and improved quality-of-life, was 82% at 5 years and at long term follow-up overall clinical response was 80%…

http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3708509/

Celebrate Life (without MS) After HSCT

It's been eight months since I left Chicago with a new immune system and a chance to rehab my body and heal my nerves. I've been amazingly healthy, braving public transit and other germ-ridden environments uneventfully, so the immune system is doing its job.

Rummaging through my travel bags, I happened to find this nice card signed by the stem cell transplant team who worked with Dr. Burt on me. I'm not an overly sentimental sort, so I won't be framing it for my wall.  But  I can't just throw it away, either. It's a reminder of  the immense amount of care I received from some extremely qualified health professionals, every one of them smart,  kind and wonderful human beings.  Thank you all!

Drug Company Kickbacks - Dollars for Docs

We depend on the expertise and integrity of doctors to do what is best for our health. When my now-ex neurologist put me on the drug Tysabri and told me the risks were manageable, I trusted him.

Previous entries in this blog show how my ex neurologist and the drugs he prescribed eventually lost my trust. I got tired of getting more and more disabled, and I got tired of drug company sales reps getting priority over me in the MS clinic waiting room. Only fear, anger, good fortune and good luck led me to Dr. Burt and HSCT to get me off the cash cow drug treadmill that had me stumbling toward a wheelchair.

Now, finally, the Affordable Care Act will require drug companies to report payments made to doctors. Part of what drove that legislation was investigative reporting and outcry from patients. The nonprofit organization Propublica has already disseminated much information. Large pharmaceutical companies such as Pfizer and Novartis began reporting their payments to doctors as a condition of settling federal whistleblower lawsuits. But the world's biggest MS drug company, Biogen Idec, has not reported anything yet.  As of tomorrow, they will be required to by law to begin reporting that money.  It's about damn time!  The Probublica article below includes a search engine to check on the payments particular doctors receive from drug companies.  It won't be complete for awhile, but it's a start that should get better over time. You owe it to yourself and your loved ones to check your health professional against this database.

What We’ve Learned From Four Years of Diving Into Dollars for Docs

Payments from pharmaceutical companies touch hundreds of thousands of doctors. 

The information is being made public under a provision of the 2010 Affordable Care Act. The law mandates disclosure of payments to doctors, dentists, chiropractors, podiatrists and optometrists for things like promotional speaking, consulting, meals, educational items and research.

It's not quite clear what the data will show — in part because the first batch will be incomplete, covering spending for only a few months at the end of 2013 — but we at ProPublica have some good guesses. That's because we have been detailing relationships between doctors and the pharmaceutical industry for the past four years as part of our Dollars for Docs project.

We've aggregated information from the websites of some large drug companies, which publish their payments as a condition of settling federal whistle-blower lawsuits alleging improper marketing or kickbacks. Today, in cooperation with the website Pharmashine, we've added data for 2013, which now covers 17 drug companies accounting for half of United States drug sales that year. (You can look up your doctor using our easy search tool.

http://www.propublica.org/article/what-weve-learned-from-four-years-of-diving-into-dollars-for-docs

Leap of Faith on a Pilates Jump Board

I was jumping today! After not jumping for two years, it was exhilarating, but also a bit terrifying on the landing. Would I come down wrong and shatter an ankle? I didn't trust my MS-ravaged  body anymore. But I trusted my Pilates teacher, Kim, to know what she was doing.  It was a leap or faith, followed by another leap, and another. My ankles are still fine. Thank you Kim!

Technically, this was assisted jumping on a Pilates jump board machine. It's simulated jumping on a horizontal plane, not real jumping through space like in a pickup basketball game or tae kwon do class. This isn't about being like Michael Jordon. It's about getting back to being able to do small jumps, like hopping over a puddle or doing a silly dance; stuff that most able-bodied people take for granted.

A Pilates jump board is a sliding contraption attached to springs that provide varying levels of resistance. If you've never been in a Pilates studio, perhaps the closest thing to a jump board you've seen is the Chuck Norris Total Gym advertised on late-night infomercials. The difference is that a jump board uses springs for resistance rather than pulleys and gravity. And a jump board is used exclusively for development of the legs and core, areas where I am in great need of rehabilitation after my wheelchair-bound MS attack in 2013.

Not everyone at New Movement Pilates is doing rehab.  Most are doing it for a workout that improves posture and body function. Ballet dancers and Pilates instructors like Kim are jump board masters, able to make using the thing look like a graceful performance event. Though I'll never wear a leotard and a dance belt, if this helps me walk better, that's beautiful enough for me.

Life is Good Without MS

I used to wake up and ask "why me?" Why was I so unlucky to get multiple sclerosis?  Now I ask a second question—why was I so astronomically very lucky to be one of the very few MS patients in the world to be treated successfully with HSCT by the world's leading immunologist, Dr. Richard Burt?  On the first question, medical experts can speculate that me getting MS was a combination of genetic susceptibility and exposure to unknown environmental factors. On #2, how did I get to do HSCT, a review of this blog back to October 2013 shows a combination of good fortune, luck, determination, and perhaps being blessed for no reason I can currently understand.

Getting MS is like winning the lottery in reverse. Most people will never get MS. Out of a U.S. population of just over 300 million, approximately 300,000 people are estimated to have MS. That's just 0.1 percent, making MS rare enough to be listed by the National Organization for Rare Diseases (NORD). MS is considered to be manageable, but have no cure. Symptoms vary from mild inconvenience, all the way to severe disability and death.  Current statistics show that people with MS often live just a long as the general population. While that is a small bit of good news for the afflicted, the stats also show that the MSer population as a whole lives 93 percent as long as those without the disease. I felt this was a necessary number to consider when weighing the risk of treatment to stop my MS with HSCT.

It's important to note that MS is NOT usually a death sentence. In fact, many successful people, both unknown and famous live with MS.  I bring up MS fatalities not to be dour and depressing, but to point out that some MS cases like mine warrant special consideration for alternative treatments such as HSCT. HSCT stopped my MS when no standard of care MS drugs could. HSCT got me out of a wheelchair and I have little doubt that HSCT saved my life. And though Dr. Burt won't call HSCT a cure for MS (he says remission), many of his patients, including me, feel we have been cured. The autoimmune attacks have been halted, we are off MS drugs, and we are now healing rather than getting worse.

Though the medical establishment positions MS as a non life-threatening disease, it does kill people directly and indirectly. A partial list of celebrities who have died from MS includes Richard Pryor, who joked from his wheelchair that MS stood for "more shit." Annette Funicello, the cutest Mouseketeer, also died from the disease, though she suffered quietly with it and said little for many years. A partial list of other celebrities who died from MS can be found here.

Though I've gotten to know many people who are living successful lives with MS, I also have known three people who have died from MS. I've also spent enough time in an MS clinic waiting room over the years to see patients with rapidly worsening conditions. The drugs were not helping them, just as they eventually stopped helping me and began making me worse.

My reasons for choosing HSCT are as follows:

1.) I was getting rapidly worse despite MS drugs. The most recent of which, Tysabri, threatened to kill me with the deadly brain infection PML, then gave me a crippling and life-threatening MS rebound attack when my neurologist attempted to transition me to another drug.

2.) HSCT is the only known treatment shown to stop MS. All current drugs, at best, merely reduce relapse frequency and slow disease progression.

3.) I was miserable from MS attacks, in pain and non-functional. MS attacks on my brainstem were aggressive and dangerous. In comparison, fatality risk of approximately 1 percent with HSCT seemed worth  it for an 85 percent chance of success in stopping the disease.

4.) Dr. Burt, one of the world's leading immunologist and the foremost expert on using HSCT to treat autoimmune diseases, accepted me as a candidate for treatment because he believed I was very likely to be helped by the procedure. Many other MS patients try to get into the program but are turned away because their MS is too far advanced. If I had waited, it was likely that I would become secondary progressive with a significantly reduced chance of successful recovery.

5.) Though my health insurance company and my now ex neurologist told me HSCT was unproven and too risky, my own research had shown me otherwise. Their standard of care had failed me and I was ready to try something new.

Now seven months after HSCT, I no longer use a wheelchair, MRI scans show my MS has been totally stopped. My nerves are healing, and an exercise program that includes specialized physical therapy and Pilates is helping me walk again.  The recovery is still a bit up and down, but the trend is toward improvement. On my best days I walk nearly a mile. One year ago, such a physical feat was only a fantasy. After a lot of bad breaks dealt by MS, it's looking like my luck has changed for the better.

MS Caused by a Virus?

Dr. Burt prescribes the antiviral drug acyclovir to MS patients he treats with chemo/HSCT. The reason he told me is that the antiviral helps prevent painful shingles outbreaks, which have tended to occur in patients after chemo.  Shingles is caused by the same herpes virus that causes chickenpox. This virus remains dormant in the body after a child gets over chickenpox, and often comes back as shingles in older adults.

Some doctors prescribe a different antiviral, amantadine, to reduce fatigue in MS patients. Whether the drug suppresses a particular virus, or a complex of viruses related to fatigue in MSers, is unknown. The Epstein-Barr virus, which causes mononucleosis, has also been correlated with MS incidence and fatigue. The MS Society has a good summary of the spotty research on viruses and MS here.

Now new research at Barts and the London, provides further evidence that viruses may play a role in MS.  The paper suggests that T cells responding to specific herpes and Epstein-Barr viruses are enriched in the spinal fluid of MSers .

The paper further suggest that treating viruses, and/or T cell memory of the viruses, may play an important role in stopping MS progression.  

Yes, I'm remembering to take my acyclovir.  : )

Immune system T cell

Self-tolerant immunity is a beautiful thing.

B cells, T cells, Antibodies, Whaaat?!!? The immune system is complicated.  The more I learn about it, the less surprised I am that mine got confused and started attacking my central nervous system. In fact, I'm amazed that this Rube Goldberg system of immune cell checks and balances works at all for anybody. And I'm so grateful that Dr. Burt figured out how to reset mine with chemo and HSCT to stop my MS.

If you want to learn the basics of immune cells, or just see some cool graphics, check out the Biolegend website. The company sells some of the test lab tools that are key to immunology research. Play around with their interactive graphic and blow your mind.

Maybe the site will inspire a young genius or two to become a next-generation immunologist. There are more than 80 different autoimmune disorders where the immune system is no longer self-tolerant. A lot of people need help, and the trend seems to be that there will be many more autoimmune diseases to come.


http://www.biolegend.com/basic_immunology

The National Institute of Health (NIH) estimates up to 23.5 million Americans* have an autoimmune disease (AD). In comparison, cancer affects up to 9 million and heart disease up to 22 million.
• NIH estimates annual direct health care costs for AD to be in the range of $100 billion (source: NIH presentation by Dr. Fauci, NIAID). In comparison, cancers costs are $57 billion (source: NIH,ACS), and heart and stroke costs are $200 billion (source: NIH, AHA).
• NIH research funding for AD in 2003 came to $591 million. In comparison, cancer funding came to $6.1 billion; and heart and stroke, to $2.4 billion (source: NIH).
• The NIH Autoimmune Diseases Research Plan states; “Research discoveries of the last decade have made autoimmune research one of the most promising areas of new discovery.”
• According to the Department of Health and Human Services’ Office of Women’s Health, autoimmune disease and disorders ranked #1 in a top ten list of most popular health topics requested by callers to the National Women’s Health Information Center.

* The American Autoimmune Related Disease Association (AARDA) says that 50 million Americans suffer from autoimmune disease. The NIH numbers only include 24 diseases for which good epidemiology studies are available.

An autoimmune disorder may affect one or more organ or tissue types. Areas often affected by autoimmune disorders include:

• Blood vessels
• Connective tissues
• Endocrine glands such as the thyroid or pancreas
• Joints
• Muscles
• Red blood cells
• Skin

A person may have more than one autoimmune disorder at the same time. Common autoimmune disorders include:

• Addison's disease
• Celiac disease - sprue (gluten-sensitive enteropathy)
• Dermatomyositis
• Graves' disease
• Hashimoto's thyroiditis
• Multiple sclerosis
• Myasthenia gravis
• Pernicious anemia
• Reactive arthritis
• Rheumatoid arthritis
• Sjogren syndrome
• Systemic lupus erythematosus
• Type I diabetes

MS Society Interviews Dr. Burt

The following MS Society Q&A with Dr. Burt is making the rounds on MS chat groups and social media. In addition to being a good view of the benefits and risks of HSCT, it's some much-deservered recognition for a great man and a procedure that offers real help, not just hope, for those MS patients who aren't helped by drugs.
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Hematopoietic Stem Cell Transplantation: An Interview with Dr. Richard Burt

By The National MS Society Aug 27, 2014 36 Comments

Could you please explain the stem-cell procedure that you’re testing?   

We are testing a procedure called hematopoietic stem-cell transplantation (HSCT), but there are a lot of misnomers that can cause confusion for people who are not familiar with HSCT. First, hematopoietic stem cells are immune stem cells. So, perhaps a better term would be immune stem cell transplantation. Second, the word “transplant” can cause confusion. When people hear it they often think of a transplant for cancer and we do not use these cancer drugs; we don’t use radiation or any cancer treatments. Nor does HSCT include transplantation of someone else’s stem cells – we give the patient their own stem cells during the procedure.

We use standard immune suppressant drugs, commonly used to treat immune or autoimmune diseases, in a very short exposure and high dose to knock down the immune system, and then we give you back your own immune stem cells that we have collected before the procedure. Giving back your immune stem cells as a supportive blood product hastens recovery, but they’re not necessary – you’d recover fine without them.

In MS, the immune inflammation that destroys myelin requires two signals to get started, one is exposure to myelin or something that looks like myelin and the second is a danger signal-something that tells the body there is a need for an immune attack. If either of these two signals are missing, you will not get the inflammation that causes MS. In HSCT, we are starting over-resetting the immune system. Think of it like a re-boot of your computer, we are wiping the hard drive clean and starting over. The immune system has to learn all over again which things to fight (pathogens like bacteria and viruses) and which things to leave alone (myelin). We think what happens in HSCT is that the immune response is exposed to myelin in the absence of the danger signal and as a consequence is rendered harmless (tolerant), unable to do any more damage.

Is there a type of MS that is most likely to benefit from HSCT?

Yes, because what we’re doing is stopping inflammation you need to treat when the disease in its inflammatory stage, which occurs in relapsing remitting MS. We don’t think this treatment will be very helpful for people with progressive forms (primary or secondary) of MS. However, there are other forms of stem cell therapy, therapies designed to promote nervous system repair that hold great promise for treatment of all forms of disease, including progressive MS.

Are you still recruiting people for your trial?

Yes we are. The trial is still open and ongoing. You can learn more here.

You mentioned you won’t treat people who are in late secondary-progressive, are there certain types of people that are particularly appropriate or should consider the trial?

The best way to answer that question is where does this approach lie in the treatment of MS? There are first-line therapies such as Avonex and Copaxone. If someone’s MS is controlled well with first-line therapy, they should stick with their current therapy. But if they’re not, and they’re having frequent relapses, they’ll go to second line therapy.

Our randomized trial is looking at people who have failed a first-line therapy and have opted for stem cell transplantation over a second-line treatment. Our goal of the trial is to establish in a randomized trial that this is the proper role for HSCT. Our early data suggests that HSCT does something that second-line therapy has never done: it reverses disability and significantly improves quality of life.

Can you explain the terms myeloabalative and non-myeloablative?

Our procedure is non-myeloablative. Non-myeloablative means that while we are removing much of the immune system with our drug regime, if we did not replace these cells with stem cells, the patient would be able to recover. Myeloablative is a procedure usually reserved for cancer therapy that completely eliminates the stem cell compartment. In this case, the patient would not be able to survive without a stem cell transplant. We feel that the myeloablative approach is too toxic for patients with MS and shouldn’t be used in people with MS.

There are different centers performing HSCT around the world, is the treatment standardized in any way?

I hope that our trial will help standardize this approach when our clinical trial data is published,. We coordinate our trial at a few other centers around the world. The trial is also being run in University of Sao Paulo, Brazil the University of Uppsala in Stockholm, Sweden. It’s just been approved at the University of Sheffield in the UK, and I’m speaking in Sydney, Australia this month, because they want to open a center there as well. It is the same trial run in all locations.

There are people who may not qualify for your trial or who are looking for other options. Is there any advice or caution you’d offer to people as they explore other options?

We have developed certain criteria for accepting patients in our trial based on our experience and understanding how this therapy works. People do sometimes get upset when they don’t qualify and sometimes they seek out other treatment centers.

Of course you can always find someone who doesn’t have our level of experience understanding the limitations of the treatment and who may treat them, and of course that is your right to make your own treatment decisions, but you have to be cautious if somebody doesn’t have limits or say ‘this approach can’t help this subset.’ This is a very powerful technique and just like anything powerful it can be abused. If used the wrong way it can have adverse effects.

In the early development of something like this, experience of the care team is very important. You want to be sure to work with an experienced center that is dedicated to this form of transplantation. This is so promising and so exciting, but it is not without risks.

Could you speak about the side effects and risks that people need to know about?

Someone could die from our therapy, this is most likely to be the result of a runaway infection. We are very good at preventing that, we’ve had no deaths in trial participants with MS. In fact, of the 150 participants I will be reporting soon, we’ve only had one infection. Our procedure is not without risk, but you can minimize it if you follow proper procedures. That highest risk period lasts about eight days while they are recovering in the clinic.

Another risk to be aware of is the potential for infertility. It’s age-dependent and many of our patients have gone on and gotten pregnant even in their 30’s. We encourage people who are concerned about infertility to consider options such as sperm or egg storage prior to the procedure.

Most people get blood transfusions during this process. There is also a small risk of becoming infected with HIV or hepatitis. Again, the risk is very small. In my lifetime, I’ve probably transplanted about 1,500 patients and I’ve never had anyone get HIV or hepatitis from a blood transfusion, but you can never say for sure that there is no risk. Finally, late complications of this procedure unique to MS that may arise in a small subset are hypo or hyperthyroidism, or more rarely a drop in platelets that may require transient medical treatment to reverse.

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Richard K. Burt, MD is Chief, Division of Immunotherapy at Northwestern University's Feinberg School of Medicine in Chicago, Illinois. An established international researcher, Dr Burt pioneered the use of hematopoietic stem cells to treat autoimmune diseases.

** Join the conversation about stem cells and MS here. **

http://www.msconnection.org/Blog/August-2014/Hematopoietic-Stem-Cell-Transplantation-An-Intervi#.U_62CW2eGYI.facebook

Pilates MS Rehab After HSCT

Some people who do HSCT to stop MS are jogging on the beach a few months later. Not me. Though HSCT has stopped my MS and a recent MRI showed my lesions are no longer inflammatory, I still have significant neuromuscular damage from my Tysabri rebound attack. Nerve healing and retraining the muscles will take time – Dr. Burt says he's seen improvements for other MS patients continue for up to three years.

Remember, I was in a wheelchair a year ago. After HSCT seven months ago, the wheelchair now goes unused. Standard PT sessions and yoga have been somewhat helpful in improving my walking, but my recovery has not been as rapid as I'd hoped.  My goal is to be able to run again, hike a few miles, carry a 70-lb canoe, and go skiing. I did all those things with ease three years ago, and I want back what MS and the drug Tysabri took from me. Since working out harder isn't an option, I have to work smarter.

Most people today know Pilates as a hipster celebrity workout craze, but Joseph Pilates first developed it to rehab wounded war veterans in the early 1900s. The past couple of years have certainly felt like a war for me, and rehab is what I need.

I've found a pilates instructor, Kim Taraschi at New Movement Pilates, who has had good success with rehabbing MS and stroke patients. My hope is that her expertise will apply to my issues as well. The Pilates reformer machine and some mat techniques can simulate the motions of running. It might be just what I need. Maybe I'll get to be a success story for HSCT AND Pilates,  but there's still much work ahead for me. No one said it would be easy.

Buck Up, Cowboy

There will come a time when you believe everything is finished. Yet that will be the beginning.

--Louis L'Amour

Everybody has MS a bit differently. For some, it's merely an inconvenience. Others, like me, experience severe symptoms including devastating fatigue, clinical depression, partial blindness, heat intolerance, bizarre sensations, extreme pain, spasms, numbness, loss of muscular control and crippling disability. It seems like the end.

What kept me going was more than hope. It was that I'd found out about HSCT and formed a plan to beat MS or die trying. Fading away was not an option. After I found Dr. Burt, he saw that he could help me. Six months after HSCT, an MRI scan now shows my MS is fully stopped. Thank you Dr. Burt! And though the HSCT procedure was not easy or cheap, it was not as miserable or dangerous as I was prepared for it to be. I have no doubt that HSCT not only stopped my MS, it saved my life.

For me, HSCT was just one step toward recovery. I have not used my wheelchair or my nursing home walker for several months now, but the MS Tysabri rebound attack that crippled me caused significant neuromuscular damage. My walking is still painful and labored. Now I'm doing physical therapy, qigong, yoga, acupuncture and pilates. When I want to give up, I just remember that walking beats the heck out of a wheelchair. And I remember that Dr. Burt and his team invested their valuable time in me.

Do you or someone your care about have MS that is getting worse despite MS drugs? Are you determined to not give up? Then apply ASAP to Dr. Burt's study or one of the reputable overseas clinics. Getting accepted to these programs takes precious time, months and perhaps years, so don't dawdle. Other patients are making it happen for themselves. I find it very encouraging that the most popular entry in my blog is Where to Get HSCT. There are a lot of determined MS patients out there.

Tysabri Rebound Study

Most of the research regarding Tysabri safety has focused on the drug causing increased risk of death from the deadly brain infection PML. Something that the drug's creator, Lawrence Steinman, warned about more than a decade ago.

What's been largely glossed over are cases like mine, where blood tests identify the risk, but removal of the drug sets up the patient for a horrific MS rebound attack. The industry seems to think that by preventing rapid death by PML, these tests represent an acceptable safety protocol for using the dangerous drug. As someone who was crippled and almost killed by such a relapse, I could not disagree more.

In this under-publicized study, 52.9% of patients taken off of Tysabri showed unusually high MRI inflammation within a year, and 9% showed severe relapses 3 to 9 months after drug cessation.

Abnormal inflammatory activity returns after natalizumab cessation in multiple sclerosis.

http://www.ncbi.nlm.nih.gov/pubmed/24876183

Tysabri Risks Greater Than Expected

A recent study has shown higher risk with the MS drug Tysabri. It may explain how I first tested JC virus negative and then became JC virus positive after two years on the drug. 

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http://www.webmd.com/multiple-sclerosis/news/20140325/new-clues-to-link-between-ms-drug-tysabri-and-rare-brain-disease

New Clues to Link Between MS Drug Tysabri and Rare Brain Disease

Researchers report drug mobilizes a kind of cell easily infected by a virus that can attack the brain

By Brenda Goodman

HealthDay Reporter

TUESDAY, March 25, 2014 (HealthDay News) -- Researchers report that they think they have figured out why some patients who take the multiple sclerosis drug Tysabri face a high risk of developing a rare, and sometimes fatal, brain infection.

A common virus that can cause the brain disease progressive multifocal leukoencephalopathy (PML) likes to infect and hide in certain blood cells that are mobilized by Tysabri, the study authors explained. Even more troubling, the researchers discovered that current tests may be missing some people who harbor the virus.

Right now, the risk of PML in patients treated with Tysabri for more than two years who also take other immune-suppressing drugs and test positive for antibodies to the virus, "is about one in 75 patients," said study author Eugene Major, a senior investigator at the U.S. National Institute of Neurological Disorders and Stroke (NINDS) in Bethesda, Md. "That's a very high risk."

"We need to be able to understand why this therapy puts patients at risk. As we further define that, we'll be able to develop better tests and better treatment decisions can be made," Major said.

In PML, the normally harmless "JC virus" attacks the white matter of the brain, stripping nerve cells of their insulation. Without this insulation, nerve cells can't effectively carry brain signals. The disease causes progressive weakness, paralysis, changes in vision and speech, and problems with thinking and memory.

According to the NINDS, 30 percent to 50 percent of patients with PML die within a few months of diagnosis. Those who survive the infection may face permanent disability.

Though most people carry the JC virus, PML is rare. It tends to strike people with suppressed immune function, such as patients with AIDS or those taking powerful immune-suppressing drugs like Tysabri.

A combination of three factors seems to put MS patients at highest risk: treatment with Tysabri for more than two years; receiving other kinds of immune-suppressing medications; and testing positive for antibodies to the JC virus.

The drug has had a troubled history. First approved by the U.S. Food and Drug Administration in November 2004, it was pulled off the market three months later after cases of PML occurred in ongoing clinical trials.

Since Tysabri was allowed back on the U.S. market in 2006 with strict prescribing conditions, more than 440 cases of PML have been reported in patients taking the drug, according to the study background. In 2010, the FDA added a warning about the heightened risk of PML to the drug's labeling.

To find out why the drug carries such a high risk of PML, researchers collected blood samples from two groups of MS patients -- those just starting treatment with Tysabri, and those who had been on the drug for more than two years. They compared those samples to blood taken from healthy volunteers.

The investigators were looking for a particular type of cell in the blood -- a kind of stem cell that turns into white blood cells called B-cell lymphocytes.

"Turns out in these MS patients treated with [Tysabri], the number of these blood stem cells is three- to 10-fold higher than you'd see normally under normal physiologic conditions," Major said.

"JC virus is able to infect these blood stem cells as they become a B lymphocyte," he explained. His working theory has been that these infected B lymphocytes then carry the infection into the brain.

To test that theory, the researchers wanted to see if they could find traces of the JC virus in circulating blood stem cells.

And they did. Of 26 patients who were just starting treatment with Tysabri, 50 percent had traces of the JC virus in their circulating blood stem cells. Of 23 patients who had taken the drug for more than two years, 44 percent had JC virus DNA in more than one kind of blood stem cell type. In contrast, only 17 percent of the 18 healthy volunteers had signs of the JC virus in those cells.

"It was somewhat surprising to us that quite a high percentage of individuals had detectable viral DNA in these blood stem cells," Major said.

But what isn't exactly clear is how this could affect their risk of developing PML. Most patients who tested positive for JC virus had only a few copies of the virus, suggesting that they were still at low risk of infection. Patients who had taken the drug for more than two years had higher virus counts than those who were just starting treatment.

"We need to look at additional patients, and follow them for a long period of time," Major said.

Perhaps most concerning, 10 study participants had evidence of the JC virus in their blood but tested negative for antibodies to it. That suggests current tests for the virus may be missing some patients who could be at high risk for PML infection, the authors explained.

An expert who was not involved in the study, which was published online March 25 in the journal JAMA Neurology, said the findings left some questions unanswered.

"Clearly, Tysabri seems to engender the release of JC virus-containing cells from the bone marrow," said Dr. Gary Birnbaum, a neurologist and director of the Multiple Sclerosis Treatment and Research Center in Golden Valley, Minn. "This could explain why risks of PML are high in patients on this drug," he noted.

"What isn't clear is why the risk escalates dramatically after two years, since JC virus-bearing cells emerge early in the course of treatment," Birnbaum pointed out.

Additionally, Birnbaum said it was "disquieting" that researchers found evidence of the JC virus in patients who then tested negative for antibodies to it.

"Thus, testing individuals for exposure to JC virus by measuring antibodies to the virus may be insufficient to fully assess their risks for developing PML," he said.

Tysabri Crippled and Almost Killed Me

My six-month evaluation post HSCT shows my MS has been stopped and all blood test levels, including thyroid, are in the normal range. I'm walking short distances without a cane and my wheelchair goes unused. It is so good to have a future to look forward to again.

Sometimes I see the unused wheelchair sitting at the back corner of my home, waiting to be donated. I'm so grateful not to need it, and I'll be glad to have it gone. But seeing the thing reminds me of the pain and the fear, and I get angry. Before I met Dr. Burt, and before I did HSCT, mismanagement of the drug Tysabri crippled and almost killed me.

I was one of the MS patients on Tysabri buying time, trying to keep the disease from getting worse. For many MS patients, Tysabri is still the best second-tier drug available, despite the risks. The problem with Tysabri is it's not meant to be used for more than two years, and until a better drug or  HSCT gets approved there's really no good alternative for patients to transition to.

This excellent Bloomberg article summarizes why MS patients are willing to risk death with Tysabri to avoid disability. Risking death to stay mobile fit my attitude about MS. I feared disability more than death. Little did I know that Tysabri would ultimately give me what I feared the most.

FDA realized the danger of PML in 2005 when patients treated with Tysabri started dying. The drug was temporarily withdrawn from the market, but Biogen convinced FDA to allow the drug to be reintroduced with more precautionary testing of patients.

Long before I knew of Dr. Burt and HSCT, I was assured by my now-ex neurologist  that the risk with Tysabri was manageable and that the drug was my best hope of avoiding disability, so I started monthly Tysabri infusions in 2010. But after two years on Tysabri, I went from success story to unfortunate statistic, when the risk management testing protocol discovered that I was at imminent risk of PML. The test that discovered I'd turned JC-positive may have saved me from death, but not the crippling nightmare that was to follow.

After my JC-positive test, my neurologist attempted to transition me off Tysabri and onto Biogen's (BG-12/Tecfidera), but delays in approval for that drug set me up for an MS rebound attack. Doctors still debate whether this attack was just the MS coming back hard, or a PML-related condition called  immune reconstitution inflammatory syndrome (IRIS). When I called the neurologist with concern that my legs were getting rapidly weaker, he assured me that it wasn't due to IRIS. He had me on IV steroids twice a week and my recent MRI looked stable, so I should have been protected.

It wasn't until I dragged myself into his office with ski poles that he started to believe that I was having a serious MS rebound from coming off Tysabri. My legs were locked up in agonizing spasms, I had double vision, and I had developed bladder and fecal incontinence. A new MRI showed I had rapidly developing new lesions on my brainstem and motor strip areas of my brain. My condition had gone from moderate to serious in a very short time. The neurologist prescribed weekly plasmapheresis to remove some of the aggressive immune system antibodies from my blood. He also prescribed an electric wheelchair. I was still living independently, but just barely. I signed up for Metro Mobility van service for the handicapped and lived in misery with a semi-permanent catheter in my chest from June to December of 2013.

My neurologist advised me to wait for FDA approval of the drug Lemtrada (Campath). When I asked him about HSCT, he advised against it. But his statistics on HSCT mortality and efficacy didn't match the data I'd reviewed. Ultimately, our discussions turned combative, and I'd had enough of following advice that had crippled me. I made plans on my own to do HSCT in Chicago with Dr. Burt. Half-way through my HSCT treatment, I learned Lemtrada was rejected by FDA in December 2013.

It's quite possible I am an unusual case and most people on Tysabri will be fine. I'm no medical expert or statistician, so I really don't know. Looking back, though, I sure wish I'd never tried it. Following is a bit more information to chew on.

Inventor of Tysabri Says He Wouldn't Prescribe It
One of the creators of Tysabri, Dr. Lawrence Steinman, realized the potential dangers of Tysabri and warned the FDA not to approve it. Steinman now says Tysabri isn't worth the risk.

According to a New York Times article in March 2005, Dr. Steinman said he had expressed his apprehensions about the drug in speeches and in an article in the journal Science in July and had been asked by Biogen executives to tone down criticism of the drug.

Biogen sales of Tysabri have caused its stock to double in less than two years. An article in Forbes praised Biogen for managing the crisis that could have destroyed the company.The label change allowing its use may push Tysabri’s global sales to $2.5 billion to $3 billion by 2016, 

While Biogen Thrives, How Many Patients Are Harmed?

We do not know how many MS patients have been harmed by Tysabri. Biogen is not required to actively seek out adverse effects, and the FDA adverse events page has no way for consumers to access the complete numbers.  

According to e-healthme, a consumer site which compiles reports by the FDA,

On Mar, 5, 2014: 90,305 people reported to have side effects when taking Tysabri. Among them, 2,943 people (3.26%) have Progressive Multifocal Leukoencephalopathy.

http://www.ehealthme.com/ds/tysabri/progressive+multifocal+leukoencephalopathy

665 people have died while on Tysabri.

http://www.ehealthme.com/ds/tysabri/death

Researchers are now discovering the JC Virus activated by Tysabri in neurons of the gray matter in people with MS.  The virus does not just show up as a demyelinating disease in white matter.  It is creating gray matter atrophy--literally, death of neurons.  This brain tissue loss can be seen on MRI.

http://www.ncbi.nlm.nih.gov/pubmed/23868420

http://www.ncbi.nlm.nih.gov/pubmed/23913509

There have been an unknown number of Tysabri deaths linked to problems other than PML, including antibody reactions, lethal relapses after withdrawal, and cancer. Deaths and injury from central nervous system PML, herpes encephalitis, CNS lymphoma, metastic melanoma, cryptococcal meningitis continue. Most of these neurologic infections do not show up until after two years of Tysabri.

Dr. Steinman is still speaking out on Tysabri--no longer to the press, but in medical presentations at universities. He has explained the "massive failure" of Tysabri trials to show PML risk, since the mice could not develop this deadly brain disease. His online powerpoint presentation on this topic has been removed from the internet, but I did find this powerpoint link that shows the efficacy and side effects of various MS drugs, including Tysabri.

MRI Results

Just finished my 6-month post HSCT review with Dr. Burt. The centerpiece of this exam was an MRI scan of my brain and spinal cord to determine if my MS has indeed been stopped.

For those of you who only read this blog to check up on my well-being or to see if you won your Vegas bet on my demise, I'll get straight to the point — HSCT has stopped my MS! Yippee! Yahoo!  Nana-nana boo-boo non-paying Blue Cross Blue Shield and ex neurologist who tried to talk me out of doing HSCT.

I WALKED the mile from the hospital back to my hotel on a beautiful summer day along a pedestrian-crowded Michigan Avenue. The walk was challenging and cane-assisted, but much easier than rolling myself in a wheelchair, which I did back in September. There's lots of physical therapy ahead of me yet.  But time is on my side for a change. It's good to have a future again!

Hey, We're Walking!

Walking isn't a big deal, unless you can't.

This time last year, I was wheelchair-bound and barely crawling. Yesterday, I walked over a mile with a cane.  Today, I'm walking around the office without any cane at all.

Thanks for the HSCT, Dr. Burt.  And thanks for the memories, Harold Ramis.  Mr. Ramis recently died of autoimmune vasculitis, one of the many diseases that HSCT is showing some promise in curing.

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   1:23

   Stripes (1981) - Hey, we're walking!

   • by ClassicsRule
   • 6 years ago
   • 192,335 views

   "There she was just walking down the street singing..." Starring Bill Murray and Harold Ramis.

https://www.youtube.com/watch?v=5AvMNXBGgpg