Interim Results Reported from Clinical Trial of Stem Cell Transplantation in People with Relapsing-Remitting MS

A nationwide team of researchers report on interim results from a small, five-year study of transplantation of the individuals’ own hematopoietic (blood cell-producing) stem cells combined with high-dose immunotherapy in 24 people with relapsing-remitting MS. This procedure aims at “rebooting” the immune system to prevent MS immune attacks against the brain and spinal cord. At three years, 78.4% of participants experienced no new disease activity. When this trial has completed its five-year duration, it will be an important addition to research needed to determine whether this approach to stem cell transplantation is safe and effective in people with MS. Richard A. Nash, MD (Colorado Blood Center Institute) and colleagues report in JAMA Neurology (Published online December 29, 2014). This study was sponsored by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health.

Background: One type of procedure that has been explored for many years in MS is called “autologous hematopoietic (blood cell-producing) stem cell transplantation” – or HSCT. This procedure has been used in attempts to “reboot” the immune system, which launches attacks on the brain and spinal cord in people with MS.

In HSCT, these stem cells (derived from a person’s own bone marrow or blood) are stored, and the rest of the individual’s immune cells are depleted usually by chemotherapy. Then the stored stem cells are reintroduced back to the individual’s bloodstream. The new stem cells migrate to the bone marrow and over time produce new cells. Eventually they repopulate the body with immune cells. The goal of this currently experimental procedure is that the new immune cells will no longer attack myelin or other brain tissue, providing the person, what is hoped to be, a completely new immune system.

The Study: Investigators enrolled 25 people who had experienced an MS relapse involving loss of neurologic function while taking disease-modifying therapies during the previous 18 months. Participants received HSCT along with high-dose immunosuppressive therapy (a regimen of treatments that profoundly suppress the immune system), and followed for five years. The primary endpoint of this study is whether participants experience “event-free survival,” meaning that they did not die or have an increase in disease activity. Disease activity is defined as any one of the following outcomes occurring: confirmed loss of neurologic function, clinical relapse, or new lesions observed on MRI scans. The current publication presents a planned analysis after three years of follow up.

Results: One individual experienced a pulmonary embolism induced by heparin (administered as part of stem cell collection), and withdrew from the study. Event-free survival at three years was 78.4%, down from 95.8% after one year. Treatment failed in five individuals. Scores on clinical scales measuring disease activity and quality of life, including the EDSS, improved significantly at three years after HSCT. Immune system analysis showed prolonged depletion of the immune cells that drive the immune attack, indicating that the immune system was indeed “rebooted.”

Two deaths occurred, one from complications due to MS progression and another due to asthma. One person experienced an MS attack, an individual who had not complied with a prednisone regimen designed to reduce this risk during collection of stem cells. There were 130 adverse events that were severe or life-threatening, mostly cytopenias (blood cell reductions) and infections.

Comment: Rigorous clinical trials of stem cell therapies are crucial to determining their safety and effectiveness in people with MS. “We look forward to seeing the completed results of this important study,” says Bruce Bebo, PhD, Executive Vice President of Research at the National MS Society. “There are significant risks involved in hematopoietic stem cell transplantation, and it’s important to ensure that this will be a safe solution for people with MS, with significant clinical benefit.”

With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, the National MS Society believes that the potential of all types of cell therapies must be explored. The Society is currently supporting 15 research projects exploring various types of stem cells, including cells derived from bone marrow, fat and skin, and has supported 70 stem cell studies over the past 10 years.

Surgery

I am recovering from surgical complications. Will be back soon.

National MS Society Invests Nearly $19 Million in New Research to Stop Multiple Sclerosis, Restore Function and End MS Forever

What do exercise, skin cells and gut bacteria have in common? They are among the new leads being explored to move us closer to a world free of MS.
The National Multiple Sclerosis Society has committed nearly $19 million to support an expected 54 new MS research projects. These are part of a comprehensive research strategy aimed at stopping MS, restoring function that has been lost, and ending the disease forever – for every single person with MS.
This financial commitment is the latest in the Society’s relentless research efforts to move us closer to a world free of MS, investing more than $50 million in 2014 alone to support 380 new and ongoing studies around the world. So that no opportunity is wasted, the Society pursues all promising paths, while focusing on three priority areas: progressive MS, nervous system repair, and wellness and lifestyle.
Just a few of the new cutting-edge research projects include a study at Stanford University using skin cells to produce repair cells for possible future use to restore nerve-insulating myelin in MS; pre-clinical studies by a commercial firm (Glialogix) to test the nervous system-protective qualities of an oral therapy repurposed to address progressive MS; a Mayo Clinic study of beneficial gut bacteria for clues to a novel therapeutic strategy for MS; and a wellness study at the University of Illinois at Urbana-Champaign testing whether an exercise program done at home can increase strength and balance and reduce falls in people with MS.
“The comprehensive nature of these new research investments is very exciting,” noted National MS Society Executive Vice President, Research Bruce Bebo, PhD.  “While we’re driving research to stop MS, restore function and end the disease forever, at the same time we’re identifying key interventions and solutions that can help people with MS live their best lives now.”  Download details about the new research awards.
Multiple sclerosis interrupts the flow of information within the brain and between the brain and the body.  Most people with MS are diagnosed between the ages of 20 and 50, with at least two to three times more women than men being diagnosed with the disease.  Worldwide, over 2.3 million people live with the unpredictable challenges of multiple sclerosis.
“MS research is a top National MS Society priority, with increasing annual investments to drive solutions for every person with MS,” Cynthia Zagieboylo, President and CEO of the Society. “We fund the entire research spectrum, propelling novel ideas into the lab, translating breakthroughs into clinical trials, and moving success in clinical trials into new treatments for people living with MS.”
To find the best research with the most promise, the National MS Society relies on more than 130 world-class scientists who volunteer their time to carefully evaluate hundreds of proposals every year.  This rigorous evaluation process assures that Society funds fuel research that delivers results in the shortest time possible.
There are FDA-approved therapies that can impact the underlying disease course in people with the more common forms of MS.  However, none of these can stop progression or reverse the damage to restore function.  National MS Society-funded research paved the way for existing therapies – none of which existed 20 years ago – and continues to be a driving force of MS research.

Anxiety and MS

By Julie Stachowiak
 
It is not often that I feel “lucky” as a person with MS, however, I do feel extremely fortunate to have never had to endure a mood disorder as a symptom of my disease. For a very brief time when I was younger, I suffered with periodic depression as a symptom of premenstrual syndrome, and that was enough to give me the tiniest glimpse into the horror of a mood disorder. When I was diagnosed with MS and learned about the variety of symptoms that I could encounter, my fear of depression and cognitive dysfunction far outweighed my fear of losing mobility.
Since depression is a well-known symptom of MS, I was shocked to learn at the 2014 ACTRIMS-ECTRIMS Meeting that more people with MS have an anxiety disorder than have depression. A study of 7786 adults with MS showed that 54.1% had “excessive symptoms of anxiety,” while 46.9% had “excessive symptoms of depression.”
It turns out that the prevalence of anxiety disorders in people with MS is roughly three times the prevalence of these disorders in the general population. More specifically, statistics show that among people with MS:

• 18.6% have general anxiety disorder at any time (compared to 5.1% of people in the general population)
• 10.0% have panic disorder (vs. 3.5% in general population)
• 8.6% have obsessive compulsive disorder (OCD) (vs. 2.5% in the general population)
• Social anxiety is also higher in people with MS than the general population.

In addition, more women with relapsing-remitting MS (RRMS) than men with RRMS are affected by anxiety disorders. People with secondary progressive MS were more likely to have symptoms of anxiety than those with other disease types.
Anxiety has received only a fraction of the attention depression has received as a disorder overall. However, it has been shown that anxiety in combination with depression, rather than anxiety or depression alone, are associated with increased thoughts of self-harm and more social problems. Despite the high prevalence in people with MS, as well as the potential risks when anxiety is combined with depression, the treatment or management of anxiety in MS has not been specifically studied. In my opinion, this is a problem, since MS symptoms can be made worse by the side effects of antianxiety drugs, which include: drowsiness and lack of energy, clumsiness, impaired thinking and memory loss, and slurred speech.
Another challenging factor is the difficulty faced by neurologists around diagnosing this disorder in their patients. There are a couple of reasons for this. People who are newly diagnosed with MS often exhibit symptoms of anxiety that may be transitory as they adjust to their diagnosis. More challenging is the overlap of symptoms between anxiety and MS. All of these extremely common MS symptoms are also symptoms of anxiety: pain, tremors, “buzzing” in their limbs, numbness, problems swallowing, tightness around the rib cage, sexual dysfunction and weak arms and legs.
What I would like to emphasize for anyone who is experiencing symptoms of an anxiety disorder or depression is that it is NOT your fault. People with these disorders can no more “pull themselves out of it” by “counting their blessings” or “looking on the bright side” than people in wheelchairs can get up and walk at will. If you are feeling any of the symptoms of these disorders, please seek professional help, preferably from a psychiatrist or other mental health professional who has experience treating people with MS.
Note: One very specific form of anxiety that was mentioned in the session was injection phobia, brought about when people have anxiety around self-injecting their MS disease modifying therapies. There has been some success in alleviating this using cognitive behavioral therapy. It is important to address injection phobia as soon as possible, as this reluctance to self-inject can lead to problems with adherence.

Live Webcast: Research Advances from the World’s Largest MS Meeting

September 13, 2014

On Saturday, September 13, 2014, join a panel of experts for a live nationwide Webcast on "Research Advances from the World’s Largest MS Meeting"
Saturday, September 13, 2014
2 – 3 pm ET (1 – 2 pm CT, Noon – 1 pm MT, 11am – Noon PT)
To register for the live webcast please click here.
Topics include:

• Progressive MS
• Genetics
• Wellness and rehabilitation
• Repair and protection

Moderator: Kate Milliken, founder, Milligrace Productions. Kate has been living with MS since 2006.
Panelists include:
Dr. Philip DeJager, Brigham and Women’s Hospital, Boston, MA
Dr. Don Mahad, University of Edinburgh, UK
Dr. Ellen Mowry, Johns Hopkins University, Baltimore, MD
Dr. Timothy Coetzee, Chief Advocacy, Services and Research Officer for the National MS Society

Register

We want to thank Genzyme, a Sanofi Company; Novartis Pharmaceuticals; Questcor Pharmaceuticals; and Walgreens Specialty Pharmacy for providing generous educational grants to make this program possible.
*For people who cannot participate in real-time, we will post the recorded version with transcript for viewing shortly after the event.

Results Published from First Human Clinical Trials of “Anti-LINGO” Myelin Repair Strategy

August 27, 2014

Results from two phase I human safety trials of an exploratory treatment aimed at repairing myelin damaged by multiple sclerosis have now been published. One to two treatments with Biogen Idec’s BIIB033 (anti-LINGO monoclonal antibody) were given by injection under the skin or into the vein of healthy volunteers and people with relapsing-remitting or secondary-progressive MS. No serious adverse safety events were reported, and although these studies were not designed to evaluate effectiveness, the results were considered positive and have led to a phase II trial, now underway in relapsing MS. The results were published on August 27, 2014 in the online journal Neurology® Neuroimmunology & Neuroinflammation.
“It’s encouraging to see an entirely new treatment strategy aimed at repairing MS myelin damage moving forward in clinical trials,” noted Dr. Timothy Coetzee, Chief Advocacy, Services and Research Officer at the National MS Society. “Repairing myelin may be the best way to protect the nervous system from MS damage, and it holds potential for restoring function that has been lost in people living with this disease,” he added.
Background: In MS, immune attacks lead to the loss of myelin that coats and protects nerve fibers in the brain and spinal cord. Repairing the nervous system was just a dream a few years ago. Today it holds significant promise as a strategy to restore the function that MS has taken from people; and reducing or stopping MS progression. This remarkable progress is due in large part to the National MS Society’s comprehensive efforts and multi-million dollar research investments. Today the Society is supporting 87 research projects in nervous system repair, with multi-year commitments totaling over $35 million.
The first human trials of anti-LINGO leverage research aimed at stimulating the body's natural healing abilities. LINGO is a protein seen in neurons and myelin-producing cells (oligodendrocytes), and blockading this protein with a monoclonal antibody called anti-LINGO has been shown to promote remyelination in animal models.
Details: In these first tests of anti-LINGO in humans, 72 healthy people and 47 people with relapsing-remitting MS or secondary-progressive MS were given anti-LINGO or inactive placebo by injection under the skin or into the vein. The participants with MS were given two treatments, two weeks apart.
All participants were monitored extensively for any signs of adverse reactions. There were no serious adverse safety events noted. The most common side effects included headache, upper respiratory tract infection, stuffy nose, GI symptoms and urinary tract infection, and these were experienced by participants who were on placebo as well as those who received doses of anti-LINGO.
Generally phase I studies are not designed to detect benefit, but largely to evaluate the safety and tolerability of exploratory therapies, to refine appropriate dosing, and to determine whether they reach their targets – in this case, the central nervous system. That is true of these trials, and there was no evidence from MRI or other tests that showed clear evidence that existing brain lesions healed from this short exposure to anti-LINGO. However, the safety, dosing and pharmacology results were considered positive and have led to the design and launch of a phase II trial by Biogen Idec, now underway in relapsing MS.

New Study Yields Clues to How Nervous System Damage Occurs in MS

Understanding the damage that occurs to the brain and spinal cord during multiple sclerosis is key to finding ways to stopping MS progression. A new study by researchers in Austria provides new clues to the type and extent of nervous system damage in MS, opening new paths for further exploration that could eventually lead to better treatments to stop MS in its tracks. Lukas Haider, MD, Josa Frischer, MD and colleagues (Medical University of Vienna) report their findings in the Journal of Neurology, Neurosurgery and Psychiatry (Published Online June 4, 2014). The study was supported by the Austrian Science Fund.
Background: MS involves immune system attacks to the brain and spinal cord. The “white matter” in the brain consists of nerve fibers, which transmit messages to, from, and throughout the brain, and myelin. Myelin, the fatty substance that surrounds and protects nerve fibers, is white in color and is a major target of the immune system in MS. The “gray matter” in the brain includes the nerve cells and several associated structures. Recent research suggests that the gray matter is also damaged by MS, may be damaged early in the disease process, and has been linked to cognitive symptoms and disease progression.
The Study: Dr. Haider’s team studied the distribution of lesions – areas of damage – in brain tissue obtained from 75 people with MS via autopsy, as well as 12 controls without MS. Using a series of sophisticated laboratory techniques, they found that damage to gray matter was most prominent in the area of the brain known as the “basal ganglia,” an area associated with motor abilities, learning, cognition, and emotion.
Both white and gray matter damage were found in people with all types of MS. The extent of gray matter damage was similar in people with all types of MS, but white matter damage was more extensive in people with progressive MS. These findings indicate that there are important differences in the mechanisms by which white and gray matter damage develops, and these differences are apparent as well when damage develops in different parts of the brain.
The team also found elevated levels of iron in gray matter lesions, which appears to be liberated from myelin-making cells during injury and which may mean that these levels play a role in nerve cell degeneration in MS. Iron has been implicated in amplifying oxidative injury (a process wherein “free radicals,” normal byproducts of bodily processes, cause tissue injury).
Conclusion: This study provides some new information on nervous system damage caused by MS. More research, which is currently underway by investigators worldwide, is needed to understand the timing of the damage and to determine how this knowledge can be translated to new approaches to stopping MS progression.