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.
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."
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.
"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."
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.
Shawn Rhea | EurekAlert!
Bristol scientists see through glass frogs' translucent camouflage
26.05.2020 | University of Bristol
Complex genetic regulation of flowering time
26.05.2020 | Christian-Albrechts-Universität zu Kiel
Early detection of tumors is extremely important in treating cancer. A new technique developed by researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from normal tissue. The work is published May 25 in the journal Nature Nanotechnology.
researchers at the University of California, Davis offers a significant advance in using magnetic resonance imaging to pick out even very small tumors from...
Microelectronics as a key technology enables numerous innovations in the field of intelligent medical technology. The Fraunhofer Institute for Biomedical Engineering IBMT coordinates the BMBF cooperative project "I-call" realizing the first electronic system for ultrasound-based, safe and interference-resistant data transmission between implants in the human body.
When microelectronic systems are used for medical applications, they have to meet high requirements in terms of biocompatibility, reliability, energy...
Thomas Heine, Professor of Theoretical Chemistry at TU Dresden, together with his team, first predicted a topological 2D polymer in 2019. Only one year later, an international team led by Italian researchers was able to synthesize these materials and experimentally prove their topological properties. For the renowned journal Nature Materials, this was the occasion to invite Thomas Heine to a News and Views article, which was published this week. Under the title "Making 2D Topological Polymers a reality" Prof. Heine describes how his theory became a reality.
Ultrathin materials are extremely interesting as building blocks for next generation nano electronic devices, as it is much easier to make circuits and other...
Scientists took a leukocyte as the blueprint and developed a microrobot that has the size, shape and moving capabilities of a white blood cell. Simulating a blood vessel in a laboratory setting, they succeeded in magnetically navigating the ball-shaped microroller through this dynamic and dense environment. The drug-delivery vehicle withstood the simulated blood flow, pushing the developments in targeted drug delivery a step further: inside the body, there is no better access route to all tissues and organs than the circulatory system. A robot that could actually travel through this finely woven web would revolutionize the minimally-invasive treatment of illnesses.
A team of scientists from the Max Planck Institute for Intelligent Systems (MPI-IS) in Stuttgart invented a tiny microrobot that resembles a white blood cell...
By studying the chemical elements on Mars today -- including carbon and oxygen -- scientists can work backwards to piece together the history of a planet that once had the conditions necessary to support life.
Weaving this story, element by element, from roughly 140 million miles (225 million kilometers) away is a painstaking process. But scientists aren't the type...
19.05.2020 | Event News
07.04.2020 | Event News
06.04.2020 | Event News
26.05.2020 | Health and Medicine
26.05.2020 | Medical Engineering
26.05.2020 | Life Sciences