Mom's Story

A discussion about Mom's Story and MS…

Archive for the tag “National MS Society”

Australian Team Finds Possible Molecular Pathway for MS Progression

Researchers from Australia report that the amount of molecules in a sequence of chemical reactions called the kynurenine pathway differs between people with MS and healthy controls, and between people with relapsing-remitting and progressive forms of MS. The kynurenine pathway is activated by chronic inflammation, and its activation may be involved in nerve damage and MS progression.  The kynurenine pathway has also been implicated in other neurological and psychiatric disorders. The MS-specific findings, and the potential use of the kynurenine pathway in a diagnostic test, will need to be explored in additional studies.

This work was funded by the National Health and Medical Research Council and Multiple Sclerosis Research Australia. The researchers used several repositories to complete these experiments – the Accelerated Cure Project for MS, The Human Brain and Spinal Fluid Resource Center (which is sponsored by the National MS Society, among others), and the Tasmanian MS Longitudinal Study.

Advertisements

Study Finds That Some Family Members of People with MS Show Possible Early Signs of the Disease without Symptoms

Summary

  • As part of a large-scale “Genes & Environment in MS” (GEMS) study to understand factors that lead to the development of multiple sclerosis, researchers analyzed the genes and backgrounds of individuals who had no symptoms of MS, but who had close family members with MS.
  • Based on that analysis, researchers identified a group of 40 women at higher risk for developing MS, and 25 women at lower risk. Extensive neurological testing and MRI scanning uncovered possible neurological abnormalities in the higher risk group, and MRI abnormalities in a small proportion of both groups.
  • “At this time, we are developing strategies to manage the risk of MS, but there is, as yet, no specific recommendation,” explains co-author Dr. Phillip De Jager. “Family members should be reassured that the vast majority of family members will not develop MS.”
  • The team (including Zongqi Xia, MD, PhD, of Brigham and Women’s Hospital, and Daniel S. Reich, MD, PhD, of National Institute of Neurological Disorders and Stroke, Bethesda, MD) has published results in JAMA Neurology (published online January 17, 2017).
  • This study was supported by the National MS Society and the National Institutes of Health, and the Society helped to recruit participants. Two of the study authors – Daniel S. Reich, MD, PhD, and Philip L. De Jager, MD, PhD – are winners of the prestigious Barancik Prize for Innovation in MS Research.

Background: An individual’s risk of developing MS increases if a close family member has MS. There is currently no way to predict which family members will develop MS. The goal of the Genes & Environment in MS (GEMS) study is to identify the genetic, environmental and immune profiles that may increase a person’s risk of developing MS.  Researchers are recruiting 5,000 subjects who have at least one first-degree relative with a diagnosis of MS. The GEMS Study is gathering genetic material (DNA) and environmental exposure history from participants as well as blood samples and brain magnetic resonance imaging (MRI) as an option. Investigators are classifying participants using the Genetic and Environmental Risk Score for MS Susceptibility (GERSMS), an experimental approach which incorporates genetic information and environmental exposures to identify people at higher or lower risk of developing MS.

The Study: As part of this large-scale, ongoing study, researchers looked at 65 women who are first-degree relatives of people with MS. The GERSMS indicated that 40 of these women were at higher risk of developing MS, and 25 women were at lower risk of developing MS. These women underwent a comprehensive neurologic examination and MRI scans.

Women in the higher risk group had less than normal vibration sensitivity in their big toes, a finding that indicates potential nerve dysfunction. A small percentage of the women in both groups had more MRI abnormalities associated with MS than one would expect to find in the general population.

The team (Zongqi Xia, MD, PhD, of Brigham and Women’s Hospital, Boston, MA, and Daniel S. Reich, MD, PhD, of National Institute of Neurological Disorders and Stroke, Bethesda, MD) has published results in JAMA Neurology (published online January 17, 2017).

This study was supported by the National MS Society and the National Institutes of Health, and the Society helped to recruit participants. Two of the study authors – Daniel S. Reich, MD, PhD, and Philip L. De Jager, MD, PhD – are winners of the prestigious Barancik Prize for Innovation in MS Research.

Next Steps:  In this study, women at high risk for MS showed possible early manifestations of the disease. “The goal of the Genes & Environment Study is to understand the sequence of events that leads someone to develop MS,” explains co-author Dr. De Jager. “At this time, we are developing strategies to manage the risk of MS, but there is, as yet, no specific recommendation. Family members should be reassured that the vast majority of family members will not develop MS.” He notes that the study did not test the possibility of preventive strategies, such as vitamin D supplementation.  “Taking vitamin D is good for bone health, and MS family members should discuss taking such supplements with their physician.”

Read more about research to find the genetic and environmental underpinnings of MS

 

New Results Show that Magnetic Stimulation of Brain May Improve Working Memory and Brain Connectivity in People with MS

Summary

  • People with MS, but not healthy controls, showed improvements in working memory, brain activity, and “connectivity” (how parts of the brain interact with one another), after treatment with Repetitive Transcranial Magnet Stimulation (rTMS). This device generates electromagnet pulses that stimulate brain activity.
  • rTMS may have a future role in cognitive rehabilitation in people with MS, but further, larger studies are necessary to confirm the safety and effectiveness of this intervention and its long-term effects.
  • The team (Hanneke Hulst, MD, of VU Medical Center in Amsterdam, and others) has published results in Journal of Neurology, Neurosurgery, and Psychiatry (Published Online First: 14 December 2016).

Background: Repetitive Transcranial Magnet Stimulation (rTMS) was approved by the FDA as a treatment for major depression. A device that generates electromagnet pulses is placed on the scalp with the idea of stimulating specific brain activity. Studies have shown that people with MS who received rTMS showed significant decreases in depression. This team looked at whether rTMS improved working memory (short-term memory needed for tasks such as mental arithmetic), which can be affected in people with MS.

The Study: Investigators administered rTMS – or a “sham” version of lower intensity – to an area of the brain associated with working memory in17 people with MS and 11 healthy controls. None of the participants showed signs of impaired memory at the outset of the study. A potential adverse event of rTMS is seizures, so participants were excluded if they were taking medicine that put them at risk for seizures, or had MS brain lesions in particular areas. Before and after, participants underwent imaging and extensive neuropsychological testing aimed at investigating memory. They also completed a working memory task while undergoing functional MRI, which measures brain activity during tasks.

At the beginning of the study, there were no differences in working memory between people with MS and controls. After treatment, the results suggested improvements among people with MS in working memory, brain activity, and “connectivity” (how parts of the brain interact with one another). These changes were not seen in controls.

The team (Hanneke Hulst, MD, of VU Medical Center in Amsterdam, and others) has published results in Journal of Neurology, Neurosurgery, and Psychiatry

Next Steps: The authors comment that this small study implies that rTMS may play a future role in cognitive rehabilitation in people with MS. However, the study is limited by the small sample size and the fact that participants did not have obvious cognitive problems. Further studies that address these factors are necessary to confirm the safety and effectiveness of this intervention for people with MS and its long-term impact on day to day activities.

Read more about cognitive changes that affect people with MS

 

Positive Results Announced from Clinical Trial of BAF-312 (Siponimod) in Secondary Progressive MS

Summary

Results presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) provided additional details from a 60-month, phase III clinical trial of the experimental oral therapy siponimod (BAF312, Novartis Pharmaceuticals AG) involving 1,651 people with secondary progressive MS.

The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression compared to those on placebo. Secondary endpoints suggested that those on active therapy had 23.4% lower average change in brain volume and reduced lesion volume.

The therapy was generally well tolerated and similar to adverse events reported for similar compounds.

Details

Background: Siponimod (BAF312) is an experimental immune system-modulating therapy that was designed to be a more selective sphingosine 1-phosphate receptor modulator than Gilenya® (fingolimod, Novartis International AG). Gilenya, was approved in 2010 for adults with relapsing forms of MS to reduce the frequency of clinical relapses and to delay the accumulation of physical disability. Siponimod previously demonstrated safety and efficacy on MRI scans in a phase II study in people with relapsing-remitting MS (The Lancet Neurology, 2013 Aug;12(8):756-67).  Siponimod is thought to act by retaining certain white blood cells in the body’s lymph nodes, keeping them out of circulation and from entering the central nervous system. Siponimod also distributes effectively to the central nervous system (brain and spinal cord) where it may have direct anti-inflammatory or other effects.

The Study: Participants were randomly assigned to take siponimod or placebo capsules daily for up to 60 months. The primary endpoint of the study was reducing the risk of disability progression, as measured by the EDSS scale at three months. Secondary endpoints included reducing the risk of disability progression as measured by the EDSS at six months versus placebo, the risk of worsening mobility as measured by the timed 25-foot walk test, disease activity as observed on MRI scans, relapse rate, and safety/ tolerability.

Results:  Results were presented at the 32nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS) on September 17, 2016. The trial met its primary endpoint of reducing the risk of disability progression compared with inactive placebo. Those on active treatment had a 21% reduced risk of disability progression (confirmed at 3 months) compared to those on placebo. Secondary endpoints suggested that those on active therapy had at 26% reduced risk of disability progression (confirmed at 6 months), a 23.4% lower average change in brain volume, and reduced MRI-detected brain lesion volume. There was no significant difference seen between groups in the timed 25-foot walk. Relapse rates were significantly lower in those taking siponimod.

Safety: The therapy was generally well tolerated and similar to adverse events reported for similar compounds. Serious adverse events occurred in 16.7% of participants. The serious adverse events reported to be more likely for those taking siponimod included nervous system disorders and infections.

Comment:
“These results suggest a modest benefit for people with secondary progressive MS, which is a positive step forward in the global effort to speed solutions for people living with this chronic form of the disease,” said Timothy Coetzee, PhD, Chief Advocacy, Services and Research Officer at the National MS Society. “We look forward to learning additional details about its potential benefit and safety.”

MS Trial Alert: Researchers Recruiting People with Relapsing MS for Antibody Study

Summary: Investigators at seven sites in the United States are recruiting at least 24 people with relapsing MS for a study of ublituximab (TG Therapeutics, Inc.), an experimental monoclonal antibody administered via intravenous infusion. At most, 100 people will be enrolled.

Rationale: Ublituximab is a new monoclonal antibody that binds to a molecule (CD20) on the surface of immune cells called B cells, and depletes them from circulation. B cells have several functions including making antibodies, and evidence suggests they play a role in immune-system mediated damage to brain and spinal cord tissues in MS. Other therapies targeting B cells (rituximab, ocrelizumab) have shown some benefit in clinical trials. Ublituximab binds to CD20 in a unique way, and thus may have greater B cell depletion capabilities than similar agents. Clinical trials are ongoing in people with blood cancer as well.

Eligibility and Details: Participants should be aged 18 to 55, have a diagnosis of relapsing MS, and have had more than one relapse in the previous two years. Further enrollment criteria are available from the contact below.

Participants are initially randomly assigned to receive either ublituximab or placebo infusions (infusions range from 1 to 4 hours).  After 28 days, participants receiving placebo will receive ublituximab.

The primary outcomes being measured are the levels of B cell depletion, and the number of participants who experience adverse events. Secondary outcomes include monitoring relapses and MRI-detected disease activity.

Contact: To learn more about the enrollment criteria for this study, and to find out if you are eligible to participate, please contact Koby Mok, PhD, via e-mail at kmok@tgtxinc.com, or by phone at 949-422-2468.

Sites are enrolling in the following cities:
Fort Collins, CO
Lexington, KY
San Antonio, TX
Knoxville, TN
Columbus, OH
Phoenix, AZ
Round Rock, TX

Download a brochure that discusses issues to think about when considering enrolling in an MS clinical trial (PDF).

Finding Solutions for the Advanced Care Needs of People with MS

While researchers are working to identify new and better strategies to stop MS, restore function and end MS forever, people whose MS has become more disabling—and their family members and friends—need information right now about how to manage the challenges they face. With these goals in mind, the National MS Society convened a group of key stakeholders – including people with MS, support partners, Society staff and clinicians from the fields of neurology, primary care, rehabilitation medicine, psychology, nursing, physical therapy and speech pathology– to help inform the Society’s role in finding solutions for individuals and families who are facing advanced care needs.

“At the Society, when we face a challenge, we get the brightest minds together and put the problems on the table,” said Cyndi Zagieboylo, President & CEO of the National MS Society. “We need to pursue every opportunity to support people with advanced MS in living their best lives.”

What It’s Like

People living with MS lent a vital voice to the process. “It’s going to be very important as you think about this that you understand our lived experience,” urged Lisa Iezzoni, MD, a health services researcher who has MS. “It takes me about 10 times longer to do the most basic task.”
Karen Jackson, who lives with primary progressive MS, agreed. “Having advanced MS means I have lost the ability to be spontaneous,” she said. “I am forced to plan every minute of every day. The only thing more exhausting than planning my day, is not planning. It takes an annoying sequence of action steps to achieve even the smallest goal, like buying gas or parking the car.”

Resilience, however, rang through despite the challenges of advanced care needs, which for both of these women includes wheeled mobility. “When people ask me how I feel about my MS, I tell them that I’m not sick,” insisted Dr. Iezzoni. “I just can’t walk.” Ms. Jackson added, “Explain to people what your needs are. They want to help.” It’s worth the effort, she says. “Not participating in life is not an option.”

If I Have to Use a Wheelchair…
Getting a wheelchair was noted to be a “line in the sand” for many people living with MS, who often view the choice to use one as a loss of independence.  Meanwhile, by trying to stay on their feet, people might be curtailing activities because of increased fatigue, or concerns about stumbling or falling.

“One of our challenges is that the wheelchair is used to symbolize disability,” said physical therapist Jean Minkel (Independence Care System. New York). “The wheelchair should not be considered a failure of therapy.”

Dr. Iezzoni heartily agrees. “When I finally started using a wheelchair 14 years after my first MS symptom, it was like spring after a housebound winter,” she said. “Silliness – that I was afraid people wouldn’t think I was strong because I was using a wheelchair.” Ms. Jackson agreed. “I’m learning to navigate a new normal,” she said. “My goal when I meet you is to have my chair disappear in 10 minutes, so that you only see me!”

Evaluating the home environment is key to determining the type of mobility device needed. “A picture is worth a thousand words and a home visit is a narrative,” said Ms. Minkel.  “To understand the need, we need to see the environment. For example, show me what the front door looks like.”

The wheeled device is not the only crucial factor – so is choosing the proper cushion to sit on. Some cushions can relieve pressure, thus preventing pressure sores (sites of damaged skin that can cause serious infections). “Thirty percent of our clients are at risk for pressure sores,” said Minkel. “Only two percent get them because they have pressure-relieving wheelchair cushions.”

The National MS Society provides guidance for people with MS and healthcare providers to navigate the process of choosing and obtaining coverage for a wheeled device.

Finding Solutions
Participants considered other key issues related to the advanced care needs of people with MS, naming some difficult problems and suggesting solutions.

  • Breathing easier — “Respiratory dysfunction begins very early in the disease process,” noted physical therapist Donna Fry, PhD (University of Michigan-Flint). But, she said, respiratory exercises can improve strength in respiratory muscles even late in the disease. Dr. Fry’s team has shown these improvements using “threshold inspiratory muscle trainers,” inexpensive devices that can help breathing muscles to get stronger. “Most clinicians are not aware of the potential early involvement of the respiratory system in people with MS and of accessible, inexpensive equipment that can enhance muscle strength,” she added.
  • Muscle spasticity — “Quite a few people with MS are experiencing significant problems from spasticity,” said neurologist Francois Bethoux, MD (Cleveland Clinic). Spasticity may be as mild as the feeling of tightness of muscles or may be so severe as to produce painful, uncontrollable spasms in the extremities, usually the legs. Dr. Bethoux believes spasticity can often be managed without specialized care. “Optimal care would involve an early diagnosis, setting realistic goals, and re-evaluation,” he said. Plus, stretching is vital, even if mobility is impaired
  • Swallowing — “We all swallow 400-500 times a day, often without knowing,” said speech-language pathologist Alex Burnham (The Boston Home). “But 30-40% of people with MS can have problems with swallowing.” The consequences can be serious – breathing in food or fluids, choking, malnutrition, dehydration, and not taking medicine. Especially later in the disease, says Mr. Burnham, swallowing and feeding issues can have dramatic effects on quality of life, especially if it limits enjoying a meal with friends and family or prevents someone from eating favorite, culturally-significant foods. Mr. Burnham advocated for screening for these problems during regular visits. “Ask patients, have you had any trouble eating? Swallowing your pills?” Burnham also mentioned novel therapies that may prove helpful, such as the “free water protocol,” in which patients are allowed to have water by itself to improve hydration. Another method is neuromuscular electrical stimulation, applied in low doses to the neck
  • Speech — Swallowing disorders can occur hand-in-hand with speech difficulties. “It’s never too early to start thinking about assistive technology, especially for people with a wide fluctuation of symptoms,” noted Mr. Burnham. “They might be fine in the morning, but then if they don’t get a nap, fatigue makes it hard for them to speak intelligibly later in the day.” Give people with MS an opportunity to use as many different modes of communication as possible, he advised. “Miscommunication can lead to frustration, social isolation, and a loss of independence,” said Mr. Burnham. “Maintaining any form of communication is critical for empowerment, relationships, and appropriate disease management.”  , including the use of smartphone applications.
  • Thinking and mood problems – “Cognitive changes are among the most prevalent reasons that people with MS are admitted to nursing homes,” said Rosalind Kalb, PhD, Vice President, Healthcare Information and Resources at the Society. “We need to be providing strategies to help people compensate for cognitive changes, and we need to speak to family members, since families may help to pick these changes up earlier.” With mood, it’s vital to understand that although depression in common in MS, some mood changes may be a natural consequence of the process of an advancing chronic disease. “People may be grieving over changes,” said Dr. Kalb. “We need to treat depression when it is present and also be respectful and comfortable with talking with people who are not depressed about how they want to live the rest of their lives.”

Achieving Optimal Care
The group discussed how to achieve optimal care for people with advanced MS.  Nicholas LaRocca, PhD, Vice President of Healthcare Delivery and Policy at the Society, noted that health care concerns are changing as the MS population gets older. “The average age of people with MS has increased by over 30 years since 1984,” he said. “Coexisting conditions, such as hypertension, increase with age and appear to be increasing in MS. Furthermore, people with MS who have some of these conditions at diagnosis reach the most severe level of mobility impairment faster than those who don’t.”

The group agreed that education is needed on both ends of this spectrum. Primary care providers need to be educated about MS so that they can distinguish MS symptoms from conditions that require primary care. And people with MS need to be educated about the importance of watching out for their own health. “A person with a disability still needs their cholesterol checked,” said Ms. Minkel. ”They still need their blood pressure checked.” Neurologists and primary care providers need to communicate, collaborate and coordinate their care of a person with MS.

Early and ongoing evaluation of symptoms also is key. “We need to educate people with MS and their caregivers about advocating for chronic care issues,” said Ruth Whitham, MD (Oregon Health& Science University). “Perhaps we can develop an advanced MS care checklist that would include symptoms to think about and what to do if you notice them.” The goal is to help people with MS to advocate for early and ongoing assessment, and for healthcare providers to ask routinely about changes that may be occurring throughout all bodily systems.
Importantly, people with MS need to know they have the right to advocate for care, regardless of how advanced their MS. “We don’t ever want a person to hear, ‘There’s nothing more we can do for you,’” added Dr. Kalb.

Caring for Caregivers
Speakers paid careful attention to how advanced care needs can affect caregivers.
“Families can become isolated,” said psychologist David Rintel, EdD, whose father lived with MS. “You feel pretty different from everyone else, and that isolation is harmful to your physical and mental health.” He advised that healthcare providers should see the caregiver occasionally along with the patient, if the patient grants permission, to get their perspective, and also see how the caregiver themselves are doing. “We need to learn the signs of burnout, such as depression, and increased use of alcohol,” he said. “Caregiver burden is real.”

There also is much that a caregiver needs to learn – navigating the healthcare system, how to transfer people safely, and management of bladder and bowel problems. “Dealing with bowel/bladder issues is actually a leading cause of caregiver burnout,” added nurse Cindy Walsh (The Boston Home).

“Families have to learn how to ask for help,” said Dr. Rintel. “They have to ask in a way where they say what, where, when and how long. Most people would help if they understood specifically what you need.”

Next Steps
The group identified the highest priority research questions that need to be answered concerning the care and support of people with advanced care needs and their families, pinpointing questions in the areas of assistive technology; comorbidities and primary care; health care system issues (e.g., insurance coverage); long-term care; symptoms and complications; skin care; speech, swallowing, and pulmonary functions; and the benefits of wellness/lifestyle interventions. They are now formulating a prioritized list of these questions to help inform the Society’s next steps.

A white paper describing the meeting’s discussion highlights and recommendations regarding the Society’s response to the needs of those affected by advanced MS will be posted on the Society’s web site, and a similar paper will be submitted for publication in a peer-reviewed journal.

Help is Available Now
Individuals nationwide may contact the Society’s MS Navigator® program via the Society’s toll-free help line 1-800-344-4867 (1-800-FIGHT MS) or via email (contactusNMSS@nmss.org). The MS Navigator Program connects people to resources,, helps people access optimal healthcare and understand benefits such as health insurance, face financial challenges and planning for the future, and find support when MS progresses.

Right now, MS activists are engaged on a number of fronts to improve quality of life and access to care. Among these is advancing home modification tax credit legislation, to provide financial relief for home modifications to promote safety and mobility.
The National MS Society provides support to people living with advanced MS, including care guides for families, information about symptom management, a guide to financial planning, and information on advanced directives. Read more

The Society also provides support for healthcare professionals who are seeking to help people with MS obtain care at home, in nursing homes, assisted living facilities, or adult day homes. Read more

 

Study Shows Expansion of Stem Cell Clinics in the U.S. and the Need for Better Oversight

Researchers have published a paper describing the proliferation of stem cell clinics in the United States and ethical issues and regulatory concerns that come with marketing unproven treatments for many conditions. Their study shows that many different types of unproven stem cell treatments are being offered, and highlights concerns for the safety of people who undergo these treatments.

There is exciting progress being made through innovative research related to the potential of many types of stem cells for slowing MS disease activity and for repairing damage to the nervous system. At present, there are no approved stem cell therapies for MS. People need the best available information to understand this exciting area of research and make decisions related to this complex issue.

The paper’s findings support the need for stem cell therapy to be explored in the context of carefully conducted clinical trials that can determine what the optimal cells, delivery methods, safety and actual effectiveness of cell therapies might be for people with MS.

Positive Results from Study of Bone Marrow-Derived Stem Cells in People with Aggressive, Relapsing MS

Summary

  • Researchers in Canada have published results of a long-term trial of an individuals’ own (autologous) hematopoietic (blood cell-producing) stem cell transplantation. The study involved 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies.
  • Three years after the procedure, 70% remained free of disease activity, with no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression.
  • None of the surviving participants, who were followed for 4 to 13 years after the procedure, experienced clinical relapses or required MS disease-modifying therapies to control their disease, and 40% experienced reductions in disability.
  • One of the participants died and another required intensive hospital care for liver complications. All participants developed fevers, which were frequently associated with infections, and other toxicities.
  • Additional research is focusing on figuring out who might benefit from this procedure and how to reduce its risks.

“These results suggest that aggressive MS may be stopped with an effective but risky procedure, for a subset of people,” said Dr. Bruce Bebo, Executive Vice President, Research, at the National MS Society. “Additional research by investigators around the world is focusing on figuring out who might benefit from this procedure and how to reduce its risks, which can include death.”

Details
Background: An experimental procedure that has been explored for several 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, the 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 by chemotherapy. Then the stored stem cells are reintroduced by infusion into the vein. The new stem cells migrate to the bone marrow and over time produce new blood cells, including immune cells. The goal of this currently experimental procedure is to establish a new immune system that no longer recognizes myelin and other nervous system tissue as dangerous. In theory, this should stop the attacks that lead to tissue damage and disability.

There are a number of laboratories around the world testing variations of HSCT for the treatment of autoimmune diseases, including MS. Preliminary findings suggest this is a promising, but potentially risky strategy for the treatment of MS.

The Study: Drs. Harold Atkins, Mark Freedman and team at the Ottawa Hospital, University of Ottawa and other institutions in Canada conducted a Phase 2 trial of HSCT that involved 24 people with aggressive relapsing-remitting MS whose disease was not controlled with available therapies. No control group was used which would have enabled comparison against the results found in the treatment group. The procedure used by this group included complete destruction of bone marrow cells and an additional step that enriched the transplanted cells for stem cells.

Results – Safety: One of the participants died of transplantation-related complications that caused liver failure and another required intensive hospital care for liver complications. The treatment regimen was modified over the course of the study to reduce toxicity, but all participants still developed fevers, which were frequently associated with infections.

Results – Effectiveness: Three years after the procedure, 70% of the participants remained free of disease activity, meaning they had no relapses, no new MRI-detected inflammatory brain lesions, and no signs of progression. The remaining 30% experienced progression of disability. In addition, for the entire follow-up period ranging from 4 to 13 years after the procedure, of the 23 survivors:

  • None experienced clinical relapse, had new active inflammatory MRI brain lesions, or required MS disease-modifying therapies to control their disease.
  • The average rate of brain atrophy (shrinkage), a measure that has been linked to MS progression, returned to levels associated with normal aging.
  • 40 percent experienced some lasting reversal of disability such as vision loss, muscle weakness and balance problems.
  • Some were able to return to work or school.

The results were published online on June 9, 2016 in The Lancet.  Major funding for the study came from the MS Society of Canada and its affiliated Multiple Sclerosis Scientific Research Foundation.

Next Steps: Rigorous clinical trials of stem cell therapies are needed to determine their safety and effectiveness in people with MS. Trials of this and other stem cell therapy approaches are taking place in Canada, the United States, Europe and elsewhere. To help explore the potential of stem cell therapy, in November 2015, the International Conference on Cell-Based Therapy for Multiple Sclerosis was convened in Lisbon, Portugal under the auspices of the International Advisory Committee on Clinical Trials in MS (a group jointly sponsored by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis). Seventy leading researchers and clinicians conferred on clinical trials needed to provide answers about which types of cells, which route of delivery, and which types and stages of disease, would be the most promising approach for treating MS. Read more about this meeting

Read more about stem cells and MS

Canadian Researchers Uncover Rare Gene that Increases Risk of Progressive MS

Researchers at the University of British Columbia have uncovered a rare gene mutation that appears to dramatically increase the risk, in some individuals, of developing a severe form of progressive multiple sclerosis. While the cause of MS is not known, scientists believe several different factors, including susceptibility genes, may interact to trigger the disease. The gene was discovered in two unrelated families that had multiple members with MS. The researchers also determined that the gene (NR1H3) contains instructions for a protein called LXRA, which is thought to be a control switch for genes involved in many functions, including some that help control inflammation and integrity of nerve-insulating myelin in the brain and spinal cord. This type of discovery can provide crucial clues to biological pathways that underlie MS, and may lead to new approaches for stopping MS and restoring function. The study, by Drs. Carles Vilariño-Güell, Weihong Song, A. Dessa Sadovnick and others, was funded in part by the MS Society of Canada and appeared in the journal Neuron on June 1, 2016.

German Study Suggests Leukemia and Colorectal Cancer Rates Increased with Mitoxantrone Use for MS

Summary

  • A study of 676 people with MS treated with the MS therapy mitoxantrone in Germany reveals that the rates of acute myeloid leukemia (a type of cancer) and colorectal cancer were significantly increased above what would be expected in the general population there. Rates of other cancers were not increased.
  • The authors note that if the findings are confirmed, recommending colonoscopy after treatment may be advisable, since if found early enough, colorectal cancer is curable.
  • The team (led by Dr. Mathias Buttmann, University of Würzburg, Germany) has published results in Neurology (published early online, May 11, 2016).

Background: Mitoxantrone is a powerful immune-suppressing therapy. Prior to its approval for use in MS, it was used only to treat certain forms of cancer. It acts in MS by suppressing the activity of immune T cells, B cells, and macrophages that are thought to lead the attack on nerve-insulating myelin. The U.S. Food and Drug Administration approved mitoxantrone for reducing neurologic disability and/or the frequency of relapses in people with secondary progressive MS or worsening relapsing-remitting MS. The total lifetime dose is limited to avoid possible heart damage. Acute myeloid leukemia has been previously reported in people treated with mitoxantrone for MS or cancer.

The Study: Investigators identified 677 people with MS seen at the University of Würzburg MS center between January 1994 and December 2007 who had received mitoxantrone. They were able to follow up with 676 of these patients.

The results show that 37 people developed cancer after taking mitoxantrone, including nine cases of breast cancer, seven cases of colorectal cancer, and four cases of acute myeloid leukemia. The rate of acute myeloid leukemia was 10 times that seen in the general population in Germany. The rate of colorectal cancer was three times that seen in the general population in Germany. The rate of breast and other cancers was not increased over that seen in the general population in Germany. Older age at treatment was associated with increased risk of cancer, but not prior use of other immunosuppressive treatments, or duration of treatment with mitoxantrone.

The team (led by Dr. Mathias Buttmann, University of Würzburg, Germany) has published results in Neurology (published early online, May 11, 2016).

Comment: The authors state that if the findings are confirmed, “posttreatment colonoscopy might improve the risk-benefit ratio of this highly active immunosuppressive drug,” since if found early enough, colorectal cancer is curable. They also note that mitoxantrone is currently the only MS therapy approved for treating secondary progressive MS, and that the overall rate of cancers may still justify the use of mitoxantrone in people who are severely affected with MS and where there are no better treatment options available.

Read more about mitoxantrone
Read more about treating secondary progressive MS
Read more about making treatment decisions in MS

 

Post Navigation