Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

UCSD researchers determine fibrin depletion decreases multiple sclerosis symptoms

20.04.2004


Tissue damage due to Multiple Sclerosis (MS) is reduced and lifespan lengthened in mouse models of the disease when a naturally occurring fibrous protein called fibrin is depleted from the body, according to researchers at the University of California, San Diego (UCSD) School of Medicine.



The study, reported online the week of April 19, 2004 in the Proceedings of the National Academy of Sciences, identifies fibrin as a potential target for therapeutic intervention in the disease, which affects an estimated one million people worldwide.

However, the research team cautions that fibrin plays an important role in blood clotting and systemic fibrin depletion could have adverse effects in a chronic disease such as MS. Therefore, additional research is needed to specifically target fibrin in the nervous system, without affecting its ability as a blood clotting protein.


"Multiple sclerosis is a nervous system disease with vascular damage, resulting from the leakage of blood proteins, including fibrin, into the brain," said the study’s first author, Katerina Akassoglous, Ph.D., a UCSD School of Medicine assistant professor of pharmacology. "Our study shows that fibrin facilitates the initiation of the inflammatory response in the nervous system and contributes to nerve tissue damage in an animal model of the disease."

MS is an autoimmune disease that affects the central nervous system (CNS), causing a variety of symptoms including loss of balance and muscle coordination, changes in cognitive function, slurred speech, bladder and bowel dysfunction, pain, and diminished vision. While the exact cause of MS is unknown, a hallmark of the disease is the loss of a material called myelin that coats nerve fibers, and the inability of the body’s natural processes to repair the damage.

Although fibrin is best known for its important role in blood clotting, recent studies have shown that fibrin accumulates in the damaged nerves of MS patients, followed by a break down of myelin. However, the cellular mechanisms of fibrin action in the central nervous system have not been known, nor have scientists determined if fibrin depletion could alleviate or lessen the symptoms of MS.

In work performed at The Rockefeller University, New York and the UCSD School of Medicine, in collaboration with colleagues at the University of Vienna, Austria and Hellenic Pasteur Institute, Greece, researchers studied normal mice and transgenic mice with an MS-like condition. The normal mice had normal spinal cords and with no fibrin deposits in the central nervous system. In contrast, the transgenic mice showed fibrin accumulation, inflammation and a degradation of the myelin in their spinal cord. When transgenic mice were bred without fibrin, they developed a later onset of the MS-like paralysis as compared to their transgenic brothers that had fibrin. In addition, the fibrin-depleted mice lived for one additional week longer than the normal, disease-impacted mice. This difference is significant in animal models such as mice that have very short lifespans.

Fibrin’s role in excessive inflammation was shown in a follow-up experiment where transgenic mice were shown to experience high expression of pro-inflammatory molecules, followed by myelin loss, as compared to the fibrin-negative transgenic mice with no signs of inflammation or myelin destruction.

In addition to the genetic deletion of fibrin, the researchers tested drug-induced fibrin depletion, which was accomplished by administering ancrod, a snake venom protein, to the transgenic mice. Consistent with the genetics-based experiments, the pharmacological depletion also delayed the onset of inflammatory myelin destruction and down-regulated the immune response. Previous studies by other investigators who used ancrod in experimental autoimmune encephalomyelitis (EAE), another animal model of MS, also showed amelioration of neurologic symptoms.

In the current study, the investigators also used cell culture studies to determine that fibrin activates macrophages, the major cell type that contributes to inflammatory myelin destruction.

Akassoglou said that "further research to identify the cellular and molecular mechanisms that fibrin utilizes in the nervous system will provide pharmacologic targets that will specifically block the actions of fibrin in nervous system disease."


The study was funded by grants from the National Institutes of Health, the Wadsworth Foundation Award, and the National Multiple Sclerosis Society.

Sidney Strickland, Ph.D., Laboratory of Neurobiology and Genetics, The Rockefeller University, New York, in whose lab Akassoglou first began her studies, was the senior author of the paper. Additional authors were Ryan Adams, Ph.D., UCSD Department of Pharmacology; Jan Bauer, Ph.D. and Hans Lassmann, M.D., Laboratory of Experimental Neuropathology, University of Vienna, Austria; Lesley Probert, Ph.D., and Vivi Tseveleki, B.Sc., Laboratory of Molecular Genetics, Hellenic Pasteur Institute, Athens, Greece; and Peter Mercado, B.Sc., The Rockefeller University

Sue Pondrom | EurekAlert!
Further information:
http://www.ucsd.edu/

More articles from Health and Medicine:

nachricht Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University

nachricht The first analysis of Ewing's sarcoma methyloma opens doors to new treatments
01.12.2016 | IDIBELL-Bellvitge Biomedical Research Institute

All articles from Health and Medicine >>>

The most recent press releases about innovation >>>

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

Im Focus: Novel silicon etching technique crafts 3-D gradient refractive index micro-optics

A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.

Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...

Im Focus: Quantum Particles Form Droplets

In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.

“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...

Im Focus: MADMAX: Max Planck Institute for Physics takes up axion research

The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.

The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...

Im Focus: Molecules change shape when wet

Broadband rotational spectroscopy unravels structural reshaping of isolated molecules in the gas phase to accommodate water

In two recent publications in the Journal of Chemical Physics and in the Journal of Physical Chemistry Letters, researchers around Melanie Schnell from the Max...

Im Focus: Fraunhofer ISE Develops Highly Compact, High Frequency DC/DC Converter for Aviation

The efficiency of power electronic systems is not solely dependent on electrical efficiency but also on weight, for example, in mobile systems. When the weight of relevant components and devices in airplanes, for instance, is reduced, fuel savings can be achieved and correspondingly greenhouse gas emissions decreased. New materials and components based on gallium nitride (GaN) can help to reduce weight and increase the efficiency. With these new materials, power electronic switches can be operated at higher switching frequency, resulting in higher power density and lower material costs.

Researchers at the Fraunhofer Institute for Solar Energy Systems ISE together with partners have investigated how these materials can be used to make power...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

ICTM Conference 2017: Production technology for turbomachine manufacturing of the future

16.11.2016 | Event News

Innovation Day Laser Technology – Laser Additive Manufacturing

01.11.2016 | Event News

#IC2S2: When Social Science meets Computer Science - GESIS will host the IC2S2 conference 2017

14.10.2016 | Event News

 
Latest News

UTSA study describes new minimally invasive device to treat cancer and other illnesses

02.12.2016 | Medical Engineering

Plasma-zapping process could yield trans fat-free soybean oil product

02.12.2016 | Agricultural and Forestry Science

What do Netflix, Google and planetary systems have in common?

02.12.2016 | Physics and Astronomy

VideoLinks
B2B-VideoLinks
More VideoLinks >>>