Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

Researchers identify how metabolites target brain-homing immune cells to treat MS

04.03.2019

The discovery could lead to novel, more specific, and more effective MS therapies and a better understanding of how the disease develops

Understanding and mitigating the role of epigenetics (environmental influences that trigger changes in gene expression) in disease development is a major goal of researchers.


Fumaric Acid Ester Metabolites act as a regulator of the micro RNA MIR-21, which is necessary to create the brain-homing T cells that are active in multiple sclerosis.

Credit: Carter Eitreim

Usage Restrictions: Use in conjunction only with this research paper

Now, a newly published paper featured on the March cover of the journal Brain adds significantly to this work by detailing how metabolites can be used to inhibit epigenetic mechanisms and effectively treat a range of diseases, including multiple sclerosis (MS).

Dimethyl fumarate (Tecfidera™)--a cell-permeable metabolite in the family of fumaric acid esters (FAEs)--is an approved treatment for MS and is potentially an effective therapy for other autoimmune diseases. The precise mechanism of the drug's action has been only partially understood, however.

In their new paper, researchers at the Advanced Science Research Center (ASRC) at The Graduate Center of The City University of New York and the Icahn School of Medicine at Mount Sinai take a major step toward unraveling the mystery by identifying a possible mechanism of action for FAEs. In doing so, they also highlight new concepts that may lay the groundwork for the development of novel classes of drugs for the treatment of MS and other diseases.

Scientists believe that MS develops when epigenetic changes cause certain brain-homing immune cells--or T cells--to attack the central nervous system. In their current paper, researchers posited that FAE metabolites work by mitigating the development of certain brain-homing T cells.

"This work has given us extremely useful insight into how we might leverage the metabolic-epigenetic interplay between cells and their environment to create new immune-modulating therapies for diseases like MS," said Patrizia Casaccia, director of the ASRC Neuroscience Initiative and a professor of genetics and neuroscience at Mount Sinai. "It may one day be possible to target and suppress production of the specific brain-homing T cells that play a role in the development of MS."

Methodology

Researchers recruited 97 volunteers with MS that were either treatment-naïve (47), FAE-treated (35), or glatiramer acetate-treated (16). Blood samples were collected from each participant and their levels of brain-homing T cells were measured by looking at the percentages of the chemokine receptors CCR4 and CCR6, which are critical to T cell trafficking between the gut, brain, and skin. The data showed significantly lower levels of these brain-homing T cells in the FAE-treated group than in the other comparison groups.

Researchers subsequently analyzed how FAEs change the epigenetic landscape of T cells to reduce the development of these pathogenic cells. Specifically, they found that FAEs have a strong epigenetic effect on a particular DNA region in T cells that includes a micro RNA called MIR-21, which is necessary to create disease-associated brain-homing T cells. Taken together, the results suggest that the immunomodulatory effect of FAEs in MS is at least in part due to the epigenetic regulation of these specific brain-homing T cells.

Significance

"Our findings about therapeutically active metabolites have implications for the treatment of not only multiple sclerosis but also other autoimmune diseases such as psoriasis and inflammatory bowel disease, which involve the same type of T cells," said Achilles Ntranos, lead author of the paper and a physician and neuroimmunology fellow at Mount Sinai Hospital whose work is supported by the Leon Levy Foundation and the National Institute of Neurological Disorders and Strokes. "Understanding the epigenetic effect of metabolites on the immune system will help us develop several novel strategies for the treatment of autoimmune diseases, which could help patients and physicians achieve better clinical outcomes."

###

Organizational Attribution

Our correct name is the Advanced Science Research Center at The Graduate Center of The City University of New York. For the purpose of space, Advanced Science Research Center, GC/CUNY is acceptable. On second reference, ASRC is correct.

About the Advanced Science Research Center

The ASRC at The Graduate Center elevates scientific research and education at CUNY and beyond through initiatives in five distinctive, but increasingly interconnected disciplines: environmental sciences, nanoscience, neuroscience, photonics, and structural biology. The ASRC promotes a collaborative, interdisciplinary research culture with renowned researchers from each of the initiatives working side by side in the ASRC's core facilities, sharing equipment that is among the most advanced available.

About The Graduate Center of The City University of New York

The Graduate Center of The City University of New York (CUNY) is a leader in public graduate education devoted to enhancing the public good through pioneering research, serious learning, and reasoned debate. The Graduate Center offers ambitious students more than 40 doctoral and master's programs of the highest caliber, taught by top faculty from throughout CUNY -- the nation's largest public urban university. Through its nearly 40 centers, institutes, and initiatives, including its Advanced Science Research Center (ASRC), The Graduate Center influences public policy and discourse and shapes innovation. The Graduate Center's extensive public programs make it a home for culture and conversation.

Media Contact

Shawn Rhea
srhea@gc.cuny.edu
212-817-7180

 @asrc_gc

http://asrc.cuny.edu 

Shawn Rhea | EurekAlert!
Further information:
http://dx.doi.org/10.1093/brain.5303708

More articles from Life Sciences:

nachricht For bacteria, the neighbors co-determine which cell dies first: The physiology of survival
17.07.2019 | Technische Universität München

nachricht Atacama Desert: Some lichens can meet their need for water from air humidity
17.07.2019 | Technische Universität Kaiserslautern

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Megakaryocytes act as „bouncers“ restraining cell migration in the bone marrow

Scientists at the University Würzburg and University Hospital of Würzburg found that megakaryocytes act as “bouncers” and thus modulate bone marrow niche properties and cell migration dynamics. The study was published in July in the Journal “Haematologica”.

Hematopoiesis is the process of forming blood cells, which occurs predominantly in the bone marrow. The bone marrow produces all types of blood cells: red...

Im Focus: Artificial neural network resolves puzzles from condensed matter physics: Which is the perfect quantum theory?

For some phenomena in quantum many-body physics several competing theories exist. But which of them describes a quantum phenomenon best? A team of researchers from the Technical University of Munich (TUM) and Harvard University in the United States has now successfully deployed artificial neural networks for image analysis of quantum systems.

Is that a dog or a cat? Such a classification is a prime example of machine learning: artificial neural networks can be trained to analyze images by looking...

Im Focus: Extremely hard yet metallically conductive: Bayreuth researchers develop novel material with high-tech prospects

An international research group led by scientists from the University of Bayreuth has produced a previously unknown material: Rhenium nitride pernitride. Thanks to combining properties that were previously considered incompatible, it looks set to become highly attractive for technological applications. Indeed, it is a super-hard metallic conductor that can withstand extremely high pressures like a diamond. A process now developed in Bayreuth opens up the possibility of producing rhenium nitride pernitride and other technologically interesting materials in sufficiently large quantity for their properties characterisation. The new findings are presented in "Nature Communications".

The possibility of finding a compound that was metallically conductive, super-hard, and ultra-incompressible was long considered unlikely in science. It was...

Im Focus: Modelling leads to the optimum size for platinum fuel cell catalysts: Activity of fuel cell catalysts doubled

An interdisciplinary research team at the Technical University of Munich (TUM) has built platinum nanoparticles for catalysis in fuel cells: The new size-optimized catalysts are twice as good as the best process commercially available today.

Fuel cells may well replace batteries as the power source for electric cars. They consume hydrogen, a gas which could be produced for example using surplus...

Im Focus: The secret of mushroom colors

Mushrooms: Darker fruiting bodies in cold climates

The fly agaric with its red hat is perhaps the most evocative of the diverse and variously colored mushroom species. Hitherto, the purpose of these colors was...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

VideoLinks
Industry & Economy
Event News

2nd International Conference on UV LED Technologies & Applications – ICULTA 2020 | Call for Abstracts

24.06.2019 | Event News

SEMANTiCS 2019 brings together industry leaders and data scientists in Karlsruhe

29.04.2019 | Event News

Revered mathematicians and computer scientists converge with 200 young researchers in Heidelberg!

17.04.2019 | Event News

 
Latest News

For bacteria, the neighbors co-determine which cell dies first: The physiology of survival

17.07.2019 | Life Sciences

Harvesting energy from the human knee

17.07.2019 | Physics and Astronomy

Neutrino-Observatorium IceCube am Südpol wird ausgebaut

17.07.2019 | Physics and Astronomy

VideoLinks
Science & Research
Overview of more VideoLinks >>>