Features | Partner Sites | Information | LinkXpress
Sign In
GLOBETECH PUBLISHING
PZ HTL SA
GLOBETECH PUBLISHING

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: Chitosan is derived from the shells of shrimp and other sea crustaceans, including Alaskan pink shrimp, pictured here (Photo courtesy of NOAA - [US] National Oceanic and Atmospheric Administration).

Chitosan Treatment Clears the Way for Antibiotics to Eliminate Recurrent Urinary Tract Infections

Recurrent urinary tract infection was successfully resolved in a mouse model by treatment with the exfoliant chitosan followed by a round of antibiotics. Bacterial urinary tract infection (UTI), most... Read more

Biochemistry

view channel

Mitochondrial Cause of Aging Can Be Reversed

Researchers have found a cause of aging in lab animals that can be reversed, possibly providing an avenue for new treatments for age-related diseases including type 2 diabetes, cancer, muscle wasting, and inflammatory diseases. The researchers plan to begin human trials late 2014. The study, which was published December... Read more

Therapeutics

view channel

Cytokine Identified That Causes Mucositis in Cancer Therapy Patients

The action of the cytokine interleukin 1-beta (IL-1beta) has been found to underlie the onset of mucositis, a common, severe side effect of chemotherapy and irradiation of cancer patients. Mucositis occurs as a result of cell death in reaction to chemo- or radiotherapy. The mucosal lining of the mouth becomes thin, may... Read more

Business

view channel

Analytical Sciences Trade Fair Declared a Rousing Success

Organizers of this year's 24th "analytica" biosciences trade fair have reported significant increases in both the number of visitors and exhibitors compared to the 2012 event. The analytica trade fair for laboratory technology, analysis, and biotechnology has been held at the Munich (Germany) Trade Fair Center every... Read more
 
Copyright © 2000-2014 Globetech Media. All rights reserved.