Inhibiting blood to save the brain

A fibrous protein called fibrinogen, found in circulating blood and important in blood clotting, can promote multiple sclerosis (MS) when it leaks from the blood into the brain, triggering inflammation that leads to MS-related nerve damage. Researchers at the University of California, San Diego (UCSD) School of Medicine have identified a fibrin-derived peptide that inhibits this specific inflammation process in mouse models of MS, reducing MS symptoms.

"Current strategies to develop therapies to fight MS primarily target T cells," said Katerina Akassoglou, Ph.D., assistant professor in UCSD's Department of Pharmacology, whose study was published in the March 19 issue of Journal of Experimental Medicine. "Blood proteins have been neglected as a therapeutic target, but this research shows that a blood clotting factor is an important player in MS."

MS is an inflammatory disease that affects the central nervous system, causing symptoms such as loss of balance and muscle coordination, and changes in cognitive function. The disease is marked by loss of myelin, a material that coats nerve fibers. Past studies showed that the destruction of the myelin sheath is associated with the accumulation of fibrinogen deposits in the brain of human MS patients. In this study, Akassoglou and colleagues showed that fibrinogen is not merely associated with the damage in MS, but an active participant. Fibrinogen activates macrophage cells in the brain called microglia, causing inflammation which damages myelin.

The scientists sought to design a therapeutic strategy that would block the damaging effects of fibrinogen without affecting its beneficial blood coagulation. Studying a mouse model, the researchers identified a specific receptor called Mac-1 that is expressed by microglial cells and binds to fibrinogen. Mice expressing a mutant form of fibrinogen that failed to bind Mac-1 had fewer inflammatory lesions and less severe MS symptoms. Blocking the interaction between Mac-1 and fibrinogen after the first episode of paralysis using the fibrin peptide prevented subsequent relapses. It also prevented further microglia activation and damage to myelin in the diseased mice, allowing them to survive with improved motor function.

"Importantly, this approach blocks fibrin's interaction with microglia, but not with platelets, so clotting wouldn't be impacted," said Akassoglou, adding that this potential MS therapy might also have applications to other blood-brain barrier diseases where blood leakage and microglia activation is present such as spinal cord injury, Alzheimer's disease or stroke.

Source: University of California - San Diego

Related stories:

Blood-clotting protein may be new target for Alzheimer's drugs
Despite the rapid rise of Alzheimer’s disease — the Alzheimer’s Association predicts as many as 7.7 million cases by 2030 — there are no preventative treatments available, few in the pharmaceutical pipeline, and those drugs being developed all share the same two molecular targets. Now Rockefeller University researchers report that by targeting a different molecule, a blood-clotting protein called fibrin, they could reduce inflammation in the brains of mice with different models of the disease.
Study in 7,000 men and women ties obesity, inflammatory proteins to heart failure risk
Heart specialists at Johns Hopkins and elsewhere report what is believed to be the first wide-scale evidence linking severe overweight to prolonged inflammation of heart tissue and the subsequent damage leading to failure of the body’s blood-pumping organ.
FDA OKs new adhesive to treat burn victims
The U.S. Food and Drug Administration approved a medical adhesive -- a fibrin sealant called Artiss -- for use in attaching skin grafts to burn patients.
Key found to breakthrough drug for clot victims
A team of researchers at Oregon Health & Science University and Washington University in St. Louis have described for the first time the mechanism that gives a mutant enzyme molecule that they have engineered – and patented – the potential to become a breakthrough drug for treating heart attacks and strokes.
Poor sleep more dangerous for women
Researchers at Duke University Medical Center say they may have figured out why poor sleep does more harm to cardiovascular health in women than in men.
Mechanism of blood clot elasticity revealed in high definition
Blood clots can save lives, staunching blood loss after injury, but they can also kill. Let loose in the bloodstream, a clot can cause a heart attack, stroke or pulmonary embolism.
Elevated inflammatory marker may be linked to increased risk of age-related eye disease
High blood levels of C-reactive protein, a substance linked to inflammation, appear to be associated with an increased risk for age-related macular degeneration, according to a report in the October issue of Archives of Ophthalmology, one of the JAMA/Archives journals.
Air pollution linked to cardiovascular risk indices in healthy young adults
Researchers in Taiwan have demonstrated for the first time that urban air pollution simultaneously affects key indicators of cardiovascular risk in young adults: inflammation, oxidative stress, coagulation and autonomic dysfunction.

News discussion:

Medicine & Health news