Features Partner Sites Information LinkXpress
Sign In
Advertise with Us
RANDOX LABORATORIES

Events

10 Oct 2016 - 12 Oct 2016
12 Nov 2016 - 16 Nov 2016

Thrombin Levels Linked to Multiple Sclerosis Progression

By BiotechDaily International staff writers
Posted on 18 Dec 2013
Print article
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



Print article

Channels

Drug Discovery

view channel
Image: Ginger is the source of a novel class of nanolipid transport vector (Photo courtesy of Georgia State University).

Ginger-Derived Doxorubicin-Loaded Nanovectors as Drug Delivery for Cancer Therapy

A novel type of nanoparticle drug transport system based on lipids isolated from ginger was used to deliver the toxic chemotherapeutic agent doxorubicin (Dox) to colon cancer cells with minimal damage... Read more

Biochemistry

view channel
Image: A space-filling model of the anticonvulsant drug carbamazepine (Photo courtesy of Wikimedia Commons).

Wastewater May Contaminate Crops with Potentially Dangerous Pharmaceuticals

Reclaimed wastewater used to irrigate crops is contaminated with pharmaceutical residues that can be detected in the urine of those who consumed such produce. Investigators at the Hebrew University... Read more

Business

view channel

Collaborative Agreement to Aid in Setting Guidelines for Evaluating Potential Ebola Therapy

Cooperation between an Israeli biopharmaceutical company and medical branches of the US government is designed to set ground rules for continued evaluation of an experimental therapy for Ebola virus disease. RedHill Biopharma Ltd. (Tel Aviv, Israel), a biopharmaceutical company primarily focused on development and c... Read more
Copyright © 2000-2016 Globetech Media. All rights reserved.