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Archive for the tag “National MS Society”

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

 

Antihistamine Shows Evidence of Stimulating Myelin Repair in Small Phase II MS Study – More studies needed before the full benefits and risks of this approach can be verified

Summary

  • In a small, phase II clinical trial, the oral antihistamine clemastine modestly improved the transmission of electrical signals in the optic nerve in participants with MS who had optic nerve damage.
  • The improved transmission indicates that nerve-insulating myelin was repaired along the nerve pathways.
  • Clemastine is an over-the-counter allergy medication. Doses in this trial exceeded the maximum recommended for over-the-counter use. Clemastine affects a range of targets in the body, and involves the risk for side effects, particularly at increased dosages.
  • This team is planning an additional trial to further determine the safety and effectiveness of clemastine, as well as studies to identify compounds that may enhance myelin repair and cause fewer side effects.
  • Clemastine was identified as having possible myelin-repairing properties through innovative preclinical research conducted by National MS Society-funded Jonah Chan, PhD, who went on to become first recipient of the Barancik Prize for Innovation in MS Research for this pioneering work.
  • Preliminary results will be presented by the clinical trial’s lead investigator Ari Green, MD (University of California, San Francisco), at the annual meeting of the American Academy of Neurology being held in Vancouver, Canada, April 15 to 21.

Background: In MS, the immune system attacks and destroys myelin, the fatty substance that surrounds and protects the nerve fibers, and the nerve fibers can also be damaged. Current therapies are largely aimed at dampening the immune attacks. However, a therapy that repairs damage to myelin and nerve fibers is also necessary.
A team at the University of California, San Francisco led by National MS Society-funded Harry Weaver Neuroscience Scholar Jonah Chan, PhD, invented a new micropillar technology to rapidly identify compounds that stimulate the regrowth of myelin. The team initiated a screen using this technology, testing a library of 1000 drugs already approved by the FDA for other conditions for their ability to promote the development of myelin-making cells and wrapping of myelin around the micropillars. Clemastine, an oral antihistamine used to treat allergy symptoms, was identified through this process. Dr. Chan was the first recipient of the Barancik Prize for Innovation in MS Research for this pioneering work.

The Clinical Trial: Ari Green, MD, led the team conducting the clinical trial. They administered oral clemastine or inactive placebo twice daily to 50 people with MS and optic nerve damage for 150 days. For the first three months of the study, people were given either clemastine or a placebo, and for the second two months, those initially given clemastine received the placebo and vice-versa. Tests were performed before and after treatment that measured visual evoked potentials. Visual evoked potentials measure transmission of electric signals along optic nerve pathways in response to stimulation. Delays in this transmission occur when the myelin is damaged and if these delays are reduced, it is an indication that myelin repair is occurring along the nerve pathways. (Participants had significant delays in transmission in at least one eye.)

Delays in visual evoked potential were reduced by 1.9 milliseconds per eye, a statistically significant result. The results hinted at a reduction in vision impairment as well, but it did not reach statistical significance. Fatigue increased mildly in participants taking clemastine.

Clemastine is an over-the-counter allergy medication. Doses in this trial exceeded the maximum recommended for over-the-counter use. Also, clemastine affects a range of targets in the body, and involves the risk for side effects, particularly at increased dosages.

Dr. Green cautions that more research with larger numbers of people is needed before doctors can recommend clemastine as a treatment for people with MS. This team is planning an additional trial to further determine the safety and effectiveness of clemastine, as well as studies to identify compounds that may enhance myelin repair and cause fewer side effects.

Drs. Green and Chan both received Society funding to launch their early careers as independent researchers focused on MS, including Harry Weaver Neuroscience Scholar Awards.

Comment: “This preliminary report is exciting, and we look forward to seeing the full results of this clinical trial of clemastine presented and then published,” says Bruce Bebo, PhD, Executive Vice President, Research at the National MS Society. “Finding a way to repair nervous system damage to restore function to people with MS is a very high research priority.”

The 2016 Annual Meeting of the American Academy of Neurology will take place in Vancouver, BC, Canada, April 15-21. The National MS Society will be providing reports summarizing studies. Anyone can get a preview of the technical summaries, or abstracts, of presentations to be given at the meeting at this link, free of charge. 

How Do You Weigh the Risks and Benefits of MS Treatments? Take a Survey Developed by Researchers Funded by the National MS Society

Summary: Investigators want to know how people living with MS weigh risks against benefits when choosing MS therapies. This 20-minute survey is funded by the National MS Society, and was developed by Robert Fox, MD, and colleagues at the Cleveland Clinic and the MS patient registry NARCOMS.

Click Here to participate in this survey.

Rationale: Although the effectiveness and risks of MS therapies are well-defined, relatively little is known about how these benefits and risks are perceived and evaluated by people with MS. This benefit/risk trade-off is important for clinicians, industry, and regulators to understand when considering which therapies to develop, approve for use, and recommend. For these reasons, the Society released a targeted request for proposals on this topic. Dr. Fox and colleagues were awarded a Health Care Policy & Delivery Research Contract to administer a large-scale survey regarding preferences related to various benefits/risks of MS therapies. They are looking for patterns of how people weigh risks and benefits based on their health status and other factors.

Goal: The results should provide a deeper understanding of various perspectives concerning risks and benefits of MS therapies among the various stakeholders involved in the development and use of MS therapies: people with MS and their care partners, clinicians, industry, and regulators such as the U.S. Food and Drug Administration.

Eligibility and Details: All people who have MS are invited to participate. The survey has a series of questions related to MS, MS therapies, and other personal characteristics; several clinical scenarios accompanied by a series of questions related to your willingness to take risks in each scenario; and questions about how you think people with MS should be involved in the government’s review of new MS therapies. The survey should take about 20 minutes to complete.

Click Here to participate in this survey

If you have questions about the survey, please contact MSregistry@narcoms.org, or 1-800-253-7884.

Read more about NARCOMS.

 

Studies Uncover Possible New Factors That Alter a Person’s Risk for Developing MS

Two recent studies have uncovered new lifestyle factors that may influence whether a person develops multiple sclerosis or not:

Harvard researchers — including National MS Society-funded Dr. Cassandra Munger — reported that children whose mothers were deficient in vitamin D during pregnancy may have nearly twice the risk of developing MS. Additional research is needed to confirm and understand this finding.

On the flip side, researchers at the Karolinska Institute in Sweden and Johns Hopkins University reported that people who drank about four cups of coffee daily had a lower risk of developing MS compared to those who did not drink coffee. Further research is needed to understand this link.

MORE: Research on risk factors is complicated, and cause and effect are difficult to establish. It’s important to note that not every mother with low levels of vitamin D will have a child who develops MS, and not everyone who drinks large amounts of coffee will avoid developing MS.

Read more about risk factors for MS

Hearing Loss and MS

Hearing loss is an uncommon symptom of MS. About 6 percent of people who have MS complain of impaired hearing; hearing loss may take place during an acute exacerbation.
In very rare cases, hearing loss has been reported as the first symptom of the disease.
Deafness due to MS is exceedingly rare, and most acute episodes of hearing deficit caused by MS tend to improve.

Hearing loss is usually associated with other symptoms that suggest damage to the brainstem — the part of the nervous system that contains the nerves that help to control vision, hearing, balance and equilibrium.

Hearing deficits caused by MS are thought to be due to inflammation and/or scarring around the eighth cranial nerve (the auditory nerve) as it enters the brainstem, although plaques (abnormal areas that develop on nerves whose myelin has been destroyed) at other sites along the auditory pathways could also contribute to hearing problems.

Because hearing deficits are so uncommon in MS, people with MS who do develop hearing loss should have their hearing thoroughly evaluated to rule out other causes.

Finding an audiologist or speech-language therapist:
The American Academy of Audiology provides an online search tool to locate audiologists who are members of the Academy. The American Speech-Language-Hearing Association (ASHA) provides an online search tool to locate certified speech-language pathologists (SLPs) and audiologists.

American Academy of Audiology
11480 Commerce Park Drive, Suite 220 Reston, VA 20191
Phone: 800-222-2336, website or email

American Speech-Language-Hearing Association (ASHA)
2200 Research Boulevard
Rockville, MD 20850-3289
Phone: 800-638-8255, website

MRI Study Yields Clues to the Development of Primary-Progressive MS

Summary

  • In a study of 453 people described as having radiologically isolated syndrome (specific areas of damage on MRI scans with no accompanying symptoms), about 12% eventually developed primary-progressive MS. This mirrors the frequency of primary-progressive MS seen in other studies of people with MS.
  • Those who developed primary-progressive MS were more likely to be men, were significantly older, and were more likely to have MS-like lesions in the spinal cord compared to those who went on to develop clinically isolated syndrome (CIS) or relapsing-remitting MS.
  • This study provides a rare glimpse of a very early stage of disease even before progression begins, and provides additional evidence of the value of research into radiologically isolated syndrome. Finding a way to identify and track primary-progressive MS earlier may help to improve access to care for those who have it.
  • The team (Dr. Orhun Kantarci, Mayo Clinic and Foundation, and national and international collaborators) published their findings in Annals of Neurology (published online, December 29, 2015).

Background: Diagnosing MS can be challenging, and it often happens in stages. The term “clinically isolated syndrome” (CIS) is used to describe a first episode of neurologic symptoms  that lasts at least 24 hours and is caused by inflammation and demyelination in one or more sites in the brain and spinal cord. Individuals who experience a CIS may or may not go on to develop definite MS. However, clinical trials of specific disease-modifying therapies have led to approvals for their use to treat CIS.

Some people have specific, “clinically silent” lesions (areas of inflamed or damaged tissue) on MRI, meaning that they are experiencing no symptoms and only have imaging findings. There has been growing research on this phenomenon, called “radiologically isolated syndrome (RIS),” which like CIS may or may not go on to develop into definite MS. There is debate as to whether people with RIS would benefit from early treatment with disease-modifying therapies.

Primary-progressive multiple sclerosis is a relatively rare form of MS, with about 10% of all people with MS receiving this diagnosis. It is characterized by steady worsening of neurologic functioning, without any distinct relapses (also called attacks or exacerbations) or periods of remission.

The Study:  This team examined data from 453 people with RIS collected from 22 investigators in five countries; a database of 210 people with MS in Olmsted County, Minnesota; and a cohort of 754 people with progressive MS.

Of the 453 people with RIS, 128 (28%) went on to develop a first neurological event consistent with CIS or relapsing MS. Of these, 15 (11.7%) developed primary-progressive MS. Those who developed primary-progressive MS were more commonly men, and older at diagnosis by approximately 10 years, than the 113 people who developed CIS/MS. The frequency of primary-progressive MS and age comparisons were similar to those identified in other groups of MS. Of the 15 who went on to develop primary-progressive MS, 12 had MRI scans of the spinal cord, and all 12 had lesions in the spinal cord, compared with 64% of those who developed CIS/MS.

The team (Dr. Orhun Kantarci, Mayo Clinic and Foundation, and national and international collaborators) published their findings in Annals of Neurology (published online, December 29, 2015).

Conclusions: This study provides a rare glimpse of a very early stage of disease even before progression begins, and provides additional evidence of the value of research into radiologically isolated syndrome. Finding a way to identify and track primary-progressive MS earlier may help to improve access to care for those who have it.

Read more about primary-progressive MS

– See more at: http://mjnickum-mynewbook.blogspot.com/#sthash.AQU8pdwj.dpuf

The Latest on Stem Cell Treatment

Recent media reports have featured news about a clinical trial involving harvesting a person’s own stem cells to treat aggressive multiple sclerosis.
• This treatment, called autologous haematopoietic stem cell transplant (HSCT), attempts to “reboot” the immune system, which is believed to launch attacks on the brain and spinal cord in people with MS.
• HSCT is under investigation in clinical trials in Canada, the United States, Europe and elsewhere. Clinical trials are needed to fully understand the benefits and risks of HSCT in MS, and who might benefit most from this approach, since it does not seem to be effective in all types of MS.
• In HSCT, stem cells 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 and over time they produce new cells that repopulate the body with immune cells.
• There is exciting progress being made through innovative research related to the potential of many types of stem cells both for slowing MS disease activity and for repairing damage to the nervous system.
• At present, there are no approved stem cell therapies for MS. Stem cell therapy is in the experimental stage, and it’s important for people to have the best available information to understand this exciting area of research and make decisions related to this complex issue.
• In November 2015, the International Conference on Cell-Based Therapy for Multiple Sclerosis was convened by the National MS Society and the European Committee for Treatment and Research in Multiple Sclerosis, bringing leading researchers and clinicians together to confer 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. A summary and consensus on next steps will be published by the conference organizers, with recommendations to help speed the development of new cell-based treatment solutions.
• With the urgent need for more effective treatments for MS, particularly for those with more progressive forms of the disease, we believe that the potential of all types of cell therapies must be explored. The Society is currently supporting 12 research projects exploring various types of stem cells, including cells derived from bone marrow, fat and skin, and has supported 68 stem cell studies over the past 10 years.

Small Pilot Trial Suggests High-Dose Vitamin D is Safe and Regulates Immune Responses in People with MS

Summary
• High-dose vitamin D supplementation increased vitamin D levels in the blood, was safe and tolerable, and reduced the proportion of immune cells that are thought to drive disease, in a small study of 40 people with relapsing-remitting MS.
• The trial was too small to detect differences in disease activity, but a larger Society sponsored trial of vitamin D supplementation is currently recruiting participants.
• The team (Elias S. Sotirchos, MD, Pavan Bhargava, MD, Peter A. Calabresi, MD, and colleagues, Johns Hopkins University School of Medicine, Baltimore) has published results in Neurology. Dr. Bhargava was funded by a Sylvia Lawry Physician Fellowship from the National MS Society.

Background: Multiple sclerosis involves immune attacks on the brain and spinal cord. A number of genetic and environmental factors influence whether a person will develop MS. These factors may also impact the severity of the disease. There is growing scientific evidence that low levels of vitamin D in the blood are a risk factor for developing MS. In lab mice, vitamin D can reduce the effects of EAE, an MS-like disease, and some evidence suggests it may impact ongoing disease activity in people who have MS.

An important initial step to pursuing this lead was to determine whether taking large doses of vitamin D was safe and provides any hints of impact against the immune activity that is associated with MS. A team at Johns Hopkins University undertook this preliminary step to determine whether a larger-scale clinical trial was warranted.

The Study: Investigators randomly assigned 40 people with MS to receive either 800 IU of vitamin D, or 10,400 IU, daily for six months (nutritional supplementation is typically 600 IU). Participants were maintained on standard disease modifying treatment throughout the course of the study. Blood tests were done at three and six months to determine whether the dose increased the levels of vitamin D in the blood, and immune system effects. Blood and urine were assessed for calcium levels, since an excess of calcium can be a side effect of high-dose vitamin D supplementation. The primary goals of this study were to determine safety and effects on immune activity markers.

The investigators reported a few adverse events that did not differ between the groups, and they were all minor.

Vitamin D levels increased more in the high-dose group, to a level that has been suggested as the optimal target for people with MS. Immune cells known as Th17 cells – which have been suggested to be major players in the immune attack on the brain and spinal cord in MS – were reduced in the high-dose group, but not in the low-dose group. Investigators also found that the higher the levels of vitamin D in the blood, the greater the reduction of Th17 cells.

Results were published in Neurology (published early online, December 30, 2015).

Next Steps: This team is now conducting a larger trial at several centers nationwide, in which they are recruiting 172 people with relapsing-remitting MS to compare the effectiveness of 600 IU of vitamin D supplementation versus 5000 IU vitamin D supplementation at reducing MS disease activity, when added to standard therapy with glatiramer acetate (Copaxone®, Teva Pharmaceutical Industries). The study is funded by a research grant from the National MS Society, with support from the Society’s Greater Delaware Valley Chapter.

Further research in the laboratory also is suggesting that vitamin D’s capabilities go beyond immune regulation. Read more

Read more about the larger, ongoing study
Read more about research on vitamin D and MS

New Study Suggests People with MS are at Increased Risk for Depression, Anxiety and other Psychiatric Disorders

Summary
• A large-scale study from Canada suggests that people with MS have increased rates of anxiety, bipolar disorder, depression, and schizophrenia compared to people without MS.
• Among people with MS, women were more likely than men to develop depression, anxiety disorder, and bipolar disorder, while men were more likely than women to develop schizophrenia. Although women with MS were more likely to develop depression than men, men developed depression at a much higher rate compared to men without MS.
• This study provides new information about the risks of psychiatric disorders in people with MS. Recognizing and addressing issues related to mental and emotional health can greatly improve quality of life for individuals and families.
• The National MS Society is focusing a light on psychosocial issues and emotional health in MS as part of its commitment to drive research and programs in wellness.
• The team (Ruth Ann Marrie, MD, PhD) published their results in Neurology (2015;85:1–8).
Details
Background: In scientific terms, having two chronic medical conditions at once is called “comorbidity.” There is growing recognition that comorbidities may complicate the diagnosis of MS and also influence disease progression, as well as an individual’s wellness and quality of life. It has long been known that depression and bipolar disorder are more common among people with MS than in the general population. In a recent study from Dr. Marrie and others, psychiatric disorders (depression and anxiety) were among the five most prevalent disorders occurring alongside MS. The current study specifically looks at psychiatric comorbidities in people with MS.

The Study: The team identified 44,452 persons with MS and 220,849 controls without the disease in administrative medical data from four Canadian provinces. They examined medical records to determine the incidence (new cases) and prevalence (all existing cases) of depression, anxiety, bipolar disorder, and schizophrenia from 1995 to 2005 among these groups.

The results show that the incidence and prevalence of anxiety, bipolar disorder, depression, and schizophrenia were all higher in people with MS than in people without MS in the control population. Among people with MS, women were more likely than men to develop depression, anxiety disorder, and bipolar disorder, while men were more likely than women to develop schizophrenia. Although women with MS were more likely to develop depression than men, men developed depression at a much higher rate compared to men without MS.

Results were published in Neurology (2015;85:1–8).

Next Steps: This study adds to a growing body of evidence on conditions that occur alongside MS. The National MS Society is focusing increased attention on psychosocial conditions in MS as part of its commitment to drive research and programs in wellness. Read more

In the face of a chronic, often progressive illness like MS, people may tend to focus primarily on their physical health and neglect their emotional health — which is an essential component of overall health and wellness. Recognizing and addressing issues related to mental and emotional health can greatly improve quality of life for individuals and families. Read more about emotional health and MS

New Lab Studies Add Evidence That High Salt Diets Increase Inflammation and May Have Implications for MS

Summary
• The results from two recently published laboratory studies suggest that high levels of salt shift the balance of the immune system toward inflammation, and that salt alters the function of several types of immune cells pertinent to MS.
• These two studies, which were both published in the Journal of Clinical Investigation, were led by Dr. David Hafler (Yale University) and Dr. Dominik Müller (Max-Delbruck Center, Berlin, Germany).
• Dr. Hafler is funded by the National MS Society to study the impact of high salt on the immune system, and the Yale team is also conducting a pilot clinical trial to explore the impact of high- and low-salt diets on MS disease activity.

Background: Eating high levels of salt, which is part of the typical Western diet, has been linked to heart disease, chronic inflammation, and cancer. Recent lab reports have also suggested that dietary salt can speed the development of the immune attack in an MS-like disease in mice, and that the mouse disease responds differently to salt depending on the gender and genetic makeup of the mice. One small study in people found a possible link between dietary salt levels and relapses in people with MS, but this study suggested a link, which is not the same as establishing an actual cause. So far, laboratory findings related to the effects of salt have been stronger than the few studies that have been reported in people. Understanding whether high dietary salt is a risk factor for developing MS or for worsening disease activity is an active area of research.

The Studies: Two studies recently published in the Journal of Clinical Investigation suggest that high dietary salt affects two types of immune cells in a way that increases inflammation, a state that is generally considered harmful in MS. A study by National MS Society-supported researchers at Yale University and Harvard Medical School led by David Hafler, MD, investigated the effects of high salt on regulatory immune cells called “Tregs.” Tregs normally suppress immune responses by other immune cells, but in people with MS Tregs have been shown to be less able to perform this helpful function to turn off attacks. The team showed in mice and in cells in lab dishes that high salt blocks the ability of Tregs to suppress potentially harmful immune cells, and shifts Tregs toward activity that increases inflammation.

The other study, by an international team led by Dominik N. Müller at the Max-Delbruck Center in Berlin, Germany, investigated immune cells called “macrophages.” This study showed that high salt blocks the activation of a subset of macrophages, reducing their ability to suppress inflammatory cells and creating an imbalance in the immune system. In mouse models, high salt diets also delayed wound healing.

Comment: Taken together, these laboratory studies add new evidence that high levels of dietary salt may increase inflammation and autoimmunity, and decrease the ability of regulatory cells and processes to limit harmful immune cell activity. More studies are needed to determine the possible role of a high-salt diet in the risk of developing MS and whether reducing salt intake may be helpful for reducing disease activity in people with MS. Dr. Hafler is funded by the National MS Society to study the impact of high salt on the immune system, and the Yale team is also conducting a pilot clinical trial to explore the impact of high- and low-salt diets on MS disease activity.

Read more about dietary factors that may play a role in MS
Read more about research on the immune system in MS

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