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Thursday, April 18, 2019
Immature Myelin-Making Cells Can Trigger Inflammation, Says New Report Funded by National MS Society
- Researchers report finding that immature myelin-making cells can form abnormal clusters on blood vessels in the brains of people with MS. Studies in mice also reveal that, instead of migrating to form new myelin, these cells disrupt the blood-brain barrier that normally protects the brain and spinal cord from damage, and also trigger immune system activity in the brain.
- Opening a research focus on the understudied area of the interactions between blood vessels and oligodendrocytes may help to identify therapeutic opportunities that could both slow down or stop myelin damaging immune activity and promote repair in MS.
- The team (Stephen Fancy, PhD, DVM, University of California, San Francisco, and colleagues) published their findings in Nature Neuroscience. (published online April 15) Dr. Fancy is a Harry Weaver Neuroscience Scholar of the National MS Society.
Background: In multiple sclerosis, myelin sheaths that insulate nerve fibers are damaged, and so are myelin-making cells called oligodendrocytes. The loss of myelin makes nerve fibers more vulnerable to injury. These myelin sheaths can be regenerated in a process called remyelination or myelin repair. Remyelination by immature oligodendrocyte precursor cells (OPCs) is critical to recovery, but myelin repair often fails, especially in the later stages of MS, contributing to disease progression. Myelin repair generally involves two stages: First, OPCs are recruited to migrate into the area of damage (lesion) from surrounding brain areas, and then the OPCs develop (“differentiate”) into mature oligodendrocytes within the lesion and start to make myelin.
A team led by Dr. Stephen Fancy at the University of California, San Francisco, investigated the idea that interactions with blood vessels that make up the “blood-brain barrier” may influence the ability of OPCs to both migrate and also properly differentiate to repair lesions. The blood-brain barrier is a system of blood vessels that controls what can enter the brain from the bloodstream, and research indicates that this barrier is disrupted early in MS, facilitating the immune response that targets the brain and spinal cord.
The Study: Dr. Fancy’s team used sophisticated microscopic imaging to examine the remyelination process in mice and in brain tissue obtained from people with MS via autopsy. They explored the possibility that OPCs use the blood vessels in the brain as a climbing frame to crawl around on and gain access to areas of damage.
The researchers observed abnormal clusters of OPCs in blood vessels near areas of active inflammation in MS tissues. To explore whether such clusters interfered with OPC migration and with blood-brain barrier integrity, they conducted extensive experiments in mice with an MS-like disease. The studies show that OPC clustering along blood vessels reduces their ability to migrate to areas of damage. Also, these OPCs interfere with several aspects of blood-brain barrier integrity, causing certain cells to be displaced and others to dysfunction – thus increasing this barrier’s leakiness and triggering inflammation in the brain.
The team published their findings in Nature Neuroscience. (published online April 15) Dr. Fancy is a Harry Weaver Neuroscience Scholar of the National MS Society.
National Multiple Sclerosis Society Commits Over $24 Million to 64 New Research Projects to Stop Multiple Sclerosis, Restore Function and End MS Forever
The National MS Society has just committed $24.4 million to support 64 new MS research projects and training fellowships. These are part of a comprehensive approach to accelerate breakthroughs by stopping multiple sclerosis, restoring function that has been lost, and ending the disease forever.
This financial commitment is the latest in the Society’s relentless research effort, investing more than $35 million in 2019 alone to support new and ongoing studies around the world, in line with our Research Priorities and commitment to supporting pathways to a cure for MS. To date, the Society has committed more than $1 billion in research funding.
Just a few of the of the new cutting-edge research projects include a phase II clinical trial at Tisch MS Research Center of New York to see if stem cells derived from individuals' own bone marrow can inhibit immune mechanisms and augment repair of nerve-insulating myelin in progressive MS; a University of Edinburgh team attempting to enhance energy production in nerve cells to protect them from damage in MS; a study in Milan, Italy analyzing how gut bacteria influence immune cell activity in the brain; and Beth Israel Deaconess Medical Center researchers in Boston asking whether treating sleep apnea can reduce MS-related fatigue. Download a summary of the new research projects
“These strategic research investments strengthen the Society’s comprehensive approach to addressing research priorities that will accelerate breakthroughs and build pathways to cures for MS,” noted Bruce Bebo, PhD, National MS Society’s Executive Vice President, Research.
“Funding research gets us closer to a cure,” said Cyndi Zagieboylo, the Society’s President and CEO. “As our new MS prevalence research shows, there are nearly 1 million people living with MS in the U.S. -- that’s twice as many as previous estimates, and it means twice as many people need solutions. If you are among the hundreds of thousands of people who participate in our fundraising events such as Walk MS, then the progress we’re seeing now is thanks to you. Ending MS will take all of us.”
The Society is the largest private funder of MS research in the world and is recognized as a global leader in driving MS research, stimulating studies worldwide, leveraging opportunities, fostering collaboration, and shaping the research landscape to find solutions for the urgent needs of people with MS.
To find the best research with the most promise, the 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.
Download a summary of the new research projects (.pdf)
Read about newly funded high-risk pilot research projects
New High-Risk Pilot Projects Explore Probiotics, Virtual Reality, Repairing MS Damage, And Other Novel Solutions For People Affected By MS
- The National MS Society has just committed funding for 14 high-risk pilot research grants to quickly test novel ideas, as part of a $24.4-million commitment to 64 new MS research and training projects focused on stopping MS, restoring what’s been lost, and ending MS forever. Additional research studies will be funded throughout the year as part of a comprehensive research program that will support 340 new and ongoing research projects in 2019 alone.
- Pilot grants are designed to quickly answer novel questions for people affected by MS, including: Can cholesterol-like molecules enhance myelin repair and restore function? Can we stop MS in its tracks by altering the gut microbiome? Can understanding more about the experience of MS in Zambia help to end the disease? Download a list of new pilot projects
- The Pilot Research Grants program is one way that the Society maintains a diverse research portfolio that includes short- and long-term investments, balances risks and rewards, and funds research globally, in line with our Research Priorities and commitment to supporting pathways to a cure for MS.
The National MS Society has just committed more than $750,000 to fund 14 high-risk pilot grants to quickly answer novel questions, as part of a $24.4-million commitment to 64 new research and training projects focused on stopping MS, restoring what’s been lost, and ending MS forever. Additional pilot studies will be funded throughout the year as part of a comprehensive research program that will support 340 new and ongoing research projects in 2019 alone.
Before investigators can get funding to test a cutting-edge research idea, they need to generate the first bit of data to prove their ideas are worth pursuing. Pilot grants allow researchers to gather preliminary data so they can apply for longer-term funding – or put the idea to rest. The grant provides one year of funding. This program is one way that the Society maintains a diverse research portfolio that includes short- and long-term investments, balances risks and rewards, and funds research globally. A survey of previous Society pilot grant recipients indicated that 90% agreed the funding was impactful to their research program.
Here are summaries of a few of the new pilot projects to which the Society has made commitments:
- Clues to repairing myelin: MS symptoms result from damage to brain and spinal cord tissues, including the loss of myelin that wraps around and supports nerve cells. Drew Adams, PhD (Case Western Reserve University, Cleveland) and his team recently reported that myelin repair can be promoted by cholesterol-like molecules. Now they are exploring how these molecules act to enhance myelin repair, by using advanced technology to obtain data on thousands of proteins that may interact with these molecules. They hope to uncover new targets for the development of novel therapeutics that promote myelin repair to improve function in people with MS.
- Prebiotics vs. Probiotics for MS: Excess inflammation associated with MS disease activity in the brain and spinal cord may in part be due to changes in the gut microbiome – millions of bacteria that live in the intestines. Rebecca Straus Farber, MD (Columbia University, New York) is leading an effort to evaluate the potentially beneficial effect of two strategies in people with MS: prebiotics (high fiber foods that act as food for bacteria) and probiotics (live microorganisms that can maintain or improve gut bacterial composition). These strategies are being compared in terms of their effects on gut bacteria content, immune system impacts, and quality of life. Results of the study, if confirmed by larger trials, could potentially identify a dietary supplement that could reduce disease activity and symptoms.
- Virtual reality to reduce pain: Pain is one of the most common symptoms in MS and often leads to disability and reduced quality of life. Leigh Charvet, PhD (New York University Langone Medical Center) and colleagues are testing whether virtual reality devices can reduce pain. Virtual reality refers to the experience of wearing a headset that allows the user to view a video or interactive space in 360° that moves as the user moves. Recently, programmers have created guided experiences that are specifically designed to distract users from pain. This small clinical trial involving people with MS who have pain will determine if this new technique has potential to reduce this troubling symptom of MS.
- Improving balance: Balance problems are a commonly experienced by people with MS, and may lead to a higher risk of falling during everyday activities. Richard Van Emmerik, PhD (University of Massachusetts, Amherst) and colleagues are testing two methods of addressing balance: tai chi (deep breathing, relaxation, and slow, gentle movements) and mindfulness meditation training (mental training that involves focusing your mind on your experiences in the present moment). Both are considered safe and can be practiced for a lifetime. This team is comparing them in an 8-week study to determine which might lead to greater improvements in physical balance and balance confidence in people with MS, and whether benefits remain after a period of not practicing.
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