Navigation Links
Gene Mutation Could Be Key to Rare Blood Vessel Disease

Finding may lead to new treatments, researcher says

WEDNESDAY, July 22 (HealthDay News) -- Mutations in a protein called thrombomodulin, which is involved in blood clotting and preventing cell damage, may be the cause of some atypical HUS, a new Canadian study suggests.

The finding might lead to new therapies for this rare disease, researchers say. There are about 300 children affected by it in the United States, and it can be fatal, according to the Foundation for Children with Atypical Hemolytic-Uremic Syndrome (aHUS).

"Identification of all of the mechanisms leading to aHUS will hopefully lead to new treatments that are currently lacking and urgently needed," said lead researcher Dr. Edward M. Conway, director of the Centre for Blood Research at the University of British Columbia Life Sciences Centre in Vancouver.

HUS is a serious condition, most often seen in children. The major cause of the disorder is damage to the endothelial cells that form the inner lining of blood vessels, Conway explained. This leads to clotting of the blood in small blood vessels, and deforming of red blood cells, causing anemia; and loss of platelets, which causes bleeding and inadequate blood supply, particularly to the kidneys, which leads to kidney failure, he said.

The trigger for the endothelial cell injury in HUS is most often a toxin that is released from bacteria after ingestion of contaminated water or food, Conway said.

"There is, however, a more rare 'atypical' form of HUS that is not induced by the bacterial toxin," he said. "In contrast to the more common form, patients with aHUS often do poorly."

Approximately 25 percent of patients with aHUS die, and about 50 percent end up needing dialysis for kidney failure, according to Conway, who added, "aHUS is seen in individuals who have, in their blood, excess activation of the so-called complement system."

The complement system is a complex set of proteins in the blood and on cells that work together to rapidly destroy any invading pathogens such as bacteria or viruses, but without damaging any of the host cells, particularly the blood vessel endothelial cells, Conway explained.

"When the system is too active and without adequate normal protective mechanisms, the endothelial cells become more easily damaged, and this places individuals at increased risk of developing aHUS," Conway said.

Mutations in different complement proteins that cause excess activation of the system and cause loss of protection to the host cells "have been identified in about 50 percent of the patients. For the rest, the etiology has remained a mystery," he said.

For the study, published in the July 23 issue of the New England Journal of Medicine, Conway's team studied 152 patients with aHUS and compared them with 380 healthy people. "In seven patients, we identified six different mutations in a protein that is on the surface of endothelial cells," he said.

The protein, called thrombomodulin, is known to prevent clotting. Using a variety of biochemical techniques, the researchers found that thrombomodulin not only protects blood from excess clotting, but it also prevents complement proteins from activating and damaging endothelial cells.

In patients with aHUS and thrombomodulin mutations, the mutated thrombomodulin was less effective at interfering with complement activation, Conway said. "Thus, the endothelial cells in these patients would be more likely to become damaged, increasing the risk of these individuals developing aHUS."

Thrombomodulin mutations only explain about 5 percent to 6 percent of aHUS cases, he noted, but for these patients it could be a breakthrough.

"It is reasonable to consider that administration of thrombomodulin might be effective as a treatment, at least for some patients with aHUS," Conway said. "Further studies, however, would be necessary to show that."

In addition, many other common diseases are associated with excess complement activation, including some types of arthritis and atherosclerosis, Conway said.

"It is reasonable to consider that thrombomodulin mutations may contribute to increasing the risk of patients developing these diseases. If that is the case, new forms of therapy might be designed for these diseases," he said.

Dr. Ajay Singh, clinical chief of the renal division and director of dialysis at Brigham and Women's Hospital in Boston, said this finding is an important addition to the understanding of this rare condition.

"This paper is a major advance," Singh said. "Since the 1970s, the role of alternative pathway complement activation has been recognized as being important in explaining the disease."

However, the precise mechanisms have been unknown, Singh said. "This paper demonstrates that mutations in the gene for thrombomodulin interfere with its ability to protect cells from complement-mediated injury. This could allow the development of therapies that could effectively treat this devastating disease," he said.

More information

For more information on atypical HUS, visit the Foundation for Children with Atypical HUS.

SOURCES: Edward M. Conway, M.D., Ph.D., director, Centre for Blood Research, and professor, medicine, University of British Columbia Life Sciences Centre, Vancouver; Ajay Singh, M.D., clinical chief, renal division, director, dialysis, Brigham and Women's Hospital, and associate professor, medicine, Harvard Medical School, Boston; July 23, 2009, New England Journal of Medicine

Copyright©2009 ScoutNews,LLC.
All rights reserved  

Related medicine news :

1. Study Shows a Link Between Schizophrenia & Genetic Mutations
2. Gene Mutation Is Linked to Heart Muscle Disease
3. JNCI news brief: Hepatitis B virus mutations may predict risk of liver cancer
4. Cancer Researchers Link DICER1 Gene Mutation to Rare Childhood Cancer
5. New Cancer Drug Fights Tumors in Those With BRCA Mutations
6. Clarient Launches New Gene Mutation Test to Help Select Therapy for Non-Small Cell Lung Cancer
7. USC researchers identify DNA mutation that occurs at beginning point of T-cell lymphoma
8. Quest Diagnostics Introduces First Comprehensive Laboratory Test To Analyze KRAS, NRAS, and BRAF Gene Mutations in Reflex Testing Service
9. Gene Mutation May Up Risks of Endometrial Cancer
10. Quest Diagnostics Discovers New Genetic Mutations Affecting Cystic Fibrosis Screening
11. First noninvasive technique to accurately predict mutations in human brain tumors
Post Your Comments:
Related Image:
Gene Mutation Could Be Key to Rare Blood Vessel Disease
(Date:11/30/2015)... , ... November 30, 2015 , ... Stress, anxiety, illness, ... a parent worry about possible tumors? , Heather Spader, MD, a new pediatric neurosurgeon ... are common, some signs might point to tumors. , “Bad headaches that ...
(Date:11/30/2015)... Minneapolis, MN (PRWEB) , ... November 30, 2015 ... ... launched at . The directory is specialized and only includes chiropractic ... is to find a competent and trustworthy alternative health practitioner when back pain ...
(Date:11/30/2015)... ... , ... The world of hair transplants and restoration is filled with methods ... procedures have been in use for many years and are among the most commonly ... has utilized many of these methods over the years, he also keeps an eye ...
(Date:11/30/2015)... ... 2015 , ... In an effort to make it easier ... information provided directly from top experts in mesothelioma, in 2016 the International ... major cities: Houston, San Francisco, and Chicago. , “For many mesothelioma patients ...
(Date:11/30/2015)... ... November 30, 2015 , ... According to an ... made a brave but slightly unusual choice to show her Instagram followers that the ... form may have been pre-mature. Saying that she didn’t “want to mislead any mommy's ...
Breaking Medicine News(10 mins):
(Date:11/30/2015)... TERRACE, Wash. and ST. LOUIS ... and Express Scripts (NASDAQ: ESRX ) today announced ... agreement. The partnership, which began in 1999, will now ... --> --> After evaluating pharmacy benefit ... Premera concluded that Express Scripts continues to offer the ...
(Date:11/30/2015)... NASHUA, N.H. , Nov. 30, 2015 /PRNewswire/ ... today that it will feature its latest solutions ... the early identification of cancer at the Radiological ... in Chicago from November ... showcase recent product advances including iReveal®, an automated ...
(Date:11/30/2015)... , Nov. 30, 2015 NHS ... further 20 TrueBeam™ machines from Varian Medical Systems ... ongoing program to replace older machines and institute ... the UK,s public hospitals. The order, placed in ... 50 licenses for Varian,s RapidArc® and Eclipse™ software ...
Breaking Medicine Technology: