Mom's Story

A discussion about Mom's Story and MS…

Archive for the tag ““chronic diseases””

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

Researchers seek volunteers for self-compassion survey

Oregon State University researchers are seeking participants for an online survey to investigate the relationship of self-compassion on resilience, physical activity, and quality of life for individuals with MS.
Subjects between the ages of 18 and 65 who can communicate in English and have a medical diagnosis of MS are eligible to participate in this study. The survey takes 20 to 30 minutes to complete. Participation in the survey is voluntary. Personal identification information will be removed from the survey data.
Survey answers will help improve understanding of the process of self-compassion and physical activity on improving health-related quality of life for individuals with MS. Results from this study will also help researchers develop effective health interventions to improve wellness and quality of life for people with MS.
To complete the survey, visit http://oregonstate.qualtrics.com/SE/?SID=SV_8ktgzQ9Jki71UEt
If you are interested or have any questions, contact the research team at nerym@onid.oregonstate.edu.

MS Trial Alert: Investigators Nationwide Recruiting People with MS for Phase I Study to Determine Safety of Experimental Antibody in Treating Relapse

Summary: Investigators nationwide are recruiting 30 people with MS for a phase I study to determine the safety and tolerability of rHIgM22, an experimental antibody. Participants may remain on their current therapy throughout the study. The study is enrolling participants experiencing a clinical acute relapse (new or worsening neurological symptoms attributable to MS preceded by a stable or improving neurological state of at least 30 days) and with at least one new, active lesion (damaged area) on MRI scans. The study is funded by Acorda Therapeutics, Inc.

Rationale: Although the body repairs some damage to nerve-insulating myelin that occurs in MS, this repair is insufficient. One strategy under study is to stimulate the body’s own internal repair capabilities. With funding from the Hilton Foundation, NIH, the National MS Society and others, Moses Rodriguez, MD, and colleagues (Mayo Clinic Foundation) identified a human antibody – rHIgM22 – that targets and attaches to myelin-making cells. When given to mice with an experimental MS-like disease, rHIgM22 promotes myelin repair. This antibody was well tolerated in another phase I study (trial NCT01803867, as listed on clinicaltrials.gov) in 55 people with all types of MS. (Abstract #P4.339, Annual Meeting of the American Academy of Neurology 2015)

Eligibility and Details: Men and women between the ages of 18 and 70 with a diagnosis of MS are eligible. The study is enrolling participants with a clinical acute relapse; an MRI will be performed to confirm that there is an active lesion (damaged area). There are detailed exclusion criteria related to laboratory, cardiac, immune and other factors. For more information on these criteria, please use the contact information below.

Participants will remain on their current therapy throughout the study. Upon entering the study with an acute relapse, subjects will receive high-dose oral steroids for five days, a standard treatment for an acute relapse. Following completion of the oral steroids for the acute relapse the subjects will receive either a single dose of rHIgM22 or placebo.

Investigators are testing 2 dose levels. For each dose, 10 participants are being randomly assigned to receive active treatment (rHIgM22) and 5 are being randomly assigned to receive inactive placebo, both via a single intravenous infusion. Blood samples will be collected from participants before and at specified times for up to 48 hours after dosing, so participants must agree to remain in the hospital for that time. Participants are being followed for 180 days after dosing, which includes return visits to the clinic and MRI scans.

The primary outcome of the study is to determine the safety and tolerability of rHIgM22 in people with MS. Adverse events are being monitored throughout the study. The investigators will also evaluate how this experimental treatment is absorbed in the body, and how the immune and nervous systems react to it. Phase I studies are the first of three stages of clinical trials that determine whether an exploratory treatment is safe and beneficial.

Contact: To learn more about the enrollment criteria for this study, and to find out if you are eligible to participate, please contact Kevin Cronin, Manager Corporate Communications, kcronin@acorda.com, 914-326-5279, or visit the trial’s listing on clinicaltrials.gov to find the site nearest you.

Sites are recruiting in the following cities:

Aurora, CO
Centennial, CO (Denver metro-area)
Dallas, TX
Indianapolis, IN
Long Beach, CA
Rochester, NY
Sacramento, CA
Saint Louis, MO
San Francisco, CA
Seattle, WA
Stanford, CA
Teaneck, NJ (NY metro area)

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

Scientists fault gene mutation for inflammation

A new mouse model study has identified a faulty “brake” within immune cells, one that should control inflammation, and points to a potential target for developing new therapies to treat multiple sclerosis. The results suggest new research models of multiple sclerosis symptoms such as movement disorders and balance control problems.
A mutation in the gene Nlrp12 was causing a malfunction in T cells. Normally, the protein the gene produces acts as a brake within T cells to control the inflammatory response. But a mutation in that gene disrupts the natural process and provokes severe inflammation. The resulting inflammation produced MS symptoms such as movement disorders and problems with balance control.
Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. However, according to researcher John Lukens, Ph.D., of the University of Virginia School of Medicine, “It’s important to note that MS is a spectrum disorder – some patients present with paralyzing conditions and some patients don’t. Not everybody’s symptoms are the same, so this might give us a glimpse into the etiology or pathogenesis of that family of MS.”

Researchers implicate chemical in MS

A new study confirms that the cytokine granulocyte macrophage colony-stimulating factor (GM-CSF) likely plays an important role in multiple sclerosis. Researchers also offer a new explanation for why the MS treatment interferon-Beta (INF-β) is often effective at reducing attacks.

Researchers, led by Abdolmohamad Rostami, M.D., Ph.D., Chair of the Department of Neurology at Thomas Jefferson University and director of its neuroimmunology laboratory, tested blood samples of patients with MS who had not yet received therapy, and those currently being treated with INF-β, a commonly used therapy. On average, untreated patients had two to three times as many immune cells producing GM-CSF as did patients being treated with INF-β, or normal subjects. Researchers looked at brain samples of deceased patients with MS and found increased numbers of GM-CSF-producing cells in comparison to normal brain samples.

“Abundant GM-CSF production at the sites of CNS inflammation suggests that GM-CSF contributes to MS pathogenesis. Our findings also reveal a potential mechanism of IFN-β therapy, namely suppression of GM-CSF production,” the authors said.

The findings were published online in the Journal of Immunology.

Experimental drug that may repair nerve damage in MS moves forward

A new study suggests that an investigational drug for multiple sclerosis (MS) may repair myelin according to a study that will be presented at the American Academy of Neurology’s 67th Annual Meeting in Washington, DC, April 18 to 25, 2015.
“This study, for the first time, provides biological evidence of repair of damaged myelin in the human brain, and advances the field of neuro-reparative therapies,” said study lead author Diego Cadavid, MD, with Biogen in Cambridge, Mass., and a fellow with the American Academy of Neurology.
The Phase 2 study involved 82 people who had their first incident of acute optic neuritis, a disease that typically affects one eye and is characterized by inflammation, damage to the nerve fibers and loss of myelin within the optic nerve. It is estimated that about half of people with optic neuritis will later develop multiple sclerosis.
All participants were treated with high dose steroids and then randomly selected with equal probability to receive either the experimental antibody, called anti-LINGO-1, or a placebo once every four weeks, for a total of six doses. Participants were then assessed every four weeks for six months and a final visit at eight months. The drug’s effectiveness in repairing myelin was evaluated by comparing the recovery of the optic nerve latency in the damaged eye at six and eight months to the normal unaffected eye at the start of the study.
The main finding of the study focused on the latency of the visual evoked potential (VEP), a test that measures the visual system’s ability to conduct electrical signals between the retina and the brain. The results showed that people treated with the experimental drug and who did not miss more than one dose (per protocol population) had significantly improved conduction as measured by latency recovery compared to people who received the placebo. At six months, those who received the drug improved on average by 7.55 milliseconds, or 34 percent, compared to placebo. The effect continued to eight months with an average improvement of 9.13 milliseconds or 41 percent over placebo.
In addition, the percentage of subjects whose VEP latency in the affected eye recovered to normal or nearly normal (within 10 percent of the normal eye) more than doubled, from 26 percent on placebo to 53 percent on the drug.
A substudy using an exploratory method of measuring latency called multifocal VEP revealed similar treatment effects.
“More studies are needed to evaluate whether these changes lead to clinical improvement,” said Cadavid.
A second study of anti-LINGO-1 in people with multiple sclerosis is ongoing.
See more at: http://www.neuroscientistnews.com/clinical-updates/experimental-drug-may-repair-nerve-damage-ms-moves-forward#sthash.KsNzebw1.dpuf

New molecule may lead to inflammation inhibitor

Scientists have developed a new drug-like molecule that can inhibit inflammation. The find has shown promise in preventing the progression of multiple sclerosis.
Walter and Eliza Hall Institute scientists have developed a small drug-like molecule called WEHI-345 that binds to and inhibits a key immune signaling protein called RIPK2. This prevents the release of inflammatory cytokines. Examining WEHI-345’s potential to treat immune diseases in experimental models of MS, it was found that WEHI-345 prevented further progression of the disease in 50 percent of cases after symptoms of MS first appeared.
Results of mouse model studies sometimes do not translate to humans and may be years away from being a marketable treatment. Calling the results extremely important, researchers said WEHI-345 had potential as an anti-inflammatory agent.
The study’s lead author, Dr Ueli Nachbur, said institute scientists would use WEHI-345 to further investigate the signaling pathway that produced inflammatory cytokines and to develop a better, stronger inhibitor of RIPK2 for treating inflammatory disease. “This signaling pathway must be finely balanced, because WEHI-345 only delayed signaling rather than blocked it. Nevertheless, this delay is enough to completely shut off cytokine production,” he said.
The research was published in the journal Nature Communications.

Give-away

The Giveaway for Mom’s Story on Amazon has ended. Thanks for participating. Mom’s Story, a Child Learns about MS is available on Amazon in paper: http://www.amazon.com/Moms-Story-Child-Learns-About/dp/147835819X/ref=tmm_pap_title_0?ie=UTF8&qid=1427210007&sr=1-1

and as an ebook on Kindle: http://www.amazon.com/Moms-Story-Mary-Nickum-ebook/dp/B00C0BO9TA/ref=tmm_kin_swatch_0?_encoding=UTF8&sr=1-1&qid=1427210007

Also Available:
http://www.barnesandnoble.com

GiveAway

Enter to win:

https://giveaway.amazon.com/p/0a71db8e470f5b54

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.

Post Navigation