Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH MEDIA
GLOBETECH PUBLISHING LLC
GLOBETECH PUBLISHING LLC

Thrombin Levels Linked to Multiple Sclerosis Progression

By BiotechDaily International staff writers
Posted on 18 Dec 2013
Image: Using advanced detection and imaging techniques, Gladstone Institutes researchers were able to track thrombin activity in mice modified to mimic MS (three samples on the left) compared to healthy controls (Photo courtesy of the University of California, San Francisco).
Image: Using advanced detection and imaging techniques, Gladstone Institutes researchers were able to track thrombin activity in mice modified to mimic MS (three samples on the left) compared to healthy controls (Photo courtesy of the University of California, San Francisco).
Results obtained from experiments that tested a novel molecular probe directed at thrombin suggested that measurement of thrombin activity might be exploited for developing sensitive probes for preclinical detection and monitoring of inflammation and progression of multiple sclerosis (MS).

MS, which affects more than 200 million people worldwide, is an inflammatory disease in which the myelin sheaths around the axons of the brain and spinal cord are damaged by autoimmune attack, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms.

Thrombin is the central protease of the blood-clotting cascade, and beyond its key role in the dynamic process of thrombus formation, thrombin has a pronounced proinflammatory character. Investigators at the Gladstone Institutes of the University of California, San Francisco (USA) had shown previously that blood seeping into the brain due to MS-induced weakening of the blood brain barrier caused a buildup of fibrin in the brain. Fibrin is produced from fibrinogen due to the action of thrombin.

In the current study, the investigators used a mouse MS model (experimental autoimmune encephalomyelitis) to characterize the activity pattern of thrombin over the course of the disease. To determine the level of thrombin, the investigators developed a thrombin-specific "Activatable Cell-Penetrating Peptide" (ACPP), a novel type of molecular probe that delivered a fluorescent agent to regions of the mouse nervous system where thrombin was active.

Results published in the November 29, 2013, online edition of the journal Annals of Neurology revealed that thrombin activity preceded onset of neurological signs, increased at disease peak, correlated with fibrin deposition, microglial activation, demyelination, axonal damage, and clinical severity. Mice with a genetic deficit in prothrombin (the precursor of thrombin) confirmed the specificity of the thrombin probe.

"We already knew that the buildup of fibrin appears early in the development of MS - both in animal models and in human patients, so we wondered whether thrombin activity could in turn serve as an early marker of disease," said senior author Dr. Katerina Akassoglou, professor of neurology at the University of California, San Francisco. "In fact, we were able to detect thrombin activity even in our animal models, before they exhibited any of the disease's neurological signs."

"In the future," said Dr. Akassoglou, "this thrombin-specific ACPP could be developed to one day allow for early patient diagnosis and therapeutic intervention - including a way to effectively monitor how patients are responding to the latest treatments."

Related Links:

Gladstone Institutes



Channels

Drug Discovery

view channel
Image: Wafers like the one shown here are used to create “organ-on-a-chip” devices to model human tissue (Photo courtesy of Dr. Anurag Mathur, University of California, Berkeley).

Human Heart-on-a-Chip Cultures May Replace Animal Models for Drug Development and Safety Screening

Human heart cells growing in an easily monitored silicon chip culture system may one day replace animal-based model systems for drug development and safety screening. Drug discovery and development... Read more

Biochemistry

view channel
Image:  Model depiction of a novel cellular mechanism by which regulation of cryptochromes Cry1 and Cry2 enables coordination of a protective transcriptional response to DNA damage caused by genotoxic stress (Photo courtesy of the journal eLife, March 2015, Papp SJ, Huber AL, et al.).

Two Proteins Critical for Circadian Cycles Protect Cells from Mutations

Scientists have discovered that two proteins critical for maintaining healthy day-night cycles also have an unexpected role in DNA repair and protecting cells against genetic mutations that could lead... Read more

Business

view channel

“Softer” Mass Spec Techniques Gain Advantage in Biomarker Discovery

Two mass spectrometry (MS) technologies, MALDI and DESI, are increasing in applications as their effectiveness is established, according to Kalorama Information (New York, NY, USA) in its report “Proteomics Markets for Research and IVD Applications (Mass Spectrometry, Chromatography, Microarrays, Electrophoresis, Immunoassays,... Read more
 
Copyright © 2000-2015 Globetech Media. All rights reserved.