Featured Research

from universities, journals, and other organizations

Discovery Promises Simpler Therapy For Sickle Cell Disease

Date:
February 2, 2005
Source:
Duke University Medical Center
Summary:
A new understanding of the causes for symptoms of sickle cell disease, a condition affecting one in every 600 African-Americans, has resulted from a study by researchers at Duke University Medical Center and Howard Hughes Medical Institute (HHMI). Their findings may lead to a new, more direct method for treating the disease, they said.

Durham, N.C. – A new understanding of the causes for symptoms of sickle cell disease, a condition affecting one in every 600 African-Americans, has resulted from a study by researchers at Duke University Medical Center and Howard Hughes Medical Institute (HHMI). Their findings may lead to a new, more direct method for treating the disease, they said.

Related Articles


Their research suggests that an inability of red blood cells to relax blood vessels through the release of nitric oxide is a major factor behind the disease's primary symptoms -- including oxygen deprivation and blocked vessels that can lead to pain, clots and stroke. Thus, therapies that restore nitric oxide to blood cells might serve as a useful method for treating the disease, said HHMI researcher Jonathan Stamler, M.D., professor of pulmonary medicine and cardiology at Duke University Medical Center.

The researchers reported their findings on Jan. 31, 2005, in an early edition of Proceedings of the National Academy of Sciences.

The symptoms of sickle cell disease have generally been attributed to the physical obstruction of blood vessels by distorted, or "sickled," and rigid red cells, Stamler said. The new findings, for the first time, implicate abnormal vessel dilation by the red cells themselves in oxygen deficiency. That oxygen deficiency, in turn, may result in sickling and, ultimately, the irreversible obstruction of blood vessels.

Relieving the vascular constriction and resulting oxygen deficiency through the restoration of nitric oxide to red cell membranes might therefore prevent the disease symptoms, opening up a new realm of therapeutic possibilities, Stamler said. Current therapies fail to treat the disease itself and are instead geared toward minimizing pain and preventing infection, he added. In patients who become anemic, blood transfusions replenish the red blood cell supply in the body.

The team further found that differences among patients in their ability to process nitric oxide in the blood correspond to the severity of their disease symptoms. That result might explain a long-standing puzzle: patients with sickle cell exhibit extreme variability in the severity of their symptoms, despite the fact that the disease stems from a single genetic defect, Stamler said.

"This finding, if verified in clinical trials, could change physicians' approach to sickle cell disease," Stamler said. "Current efforts for managing the disease completely miss the role that red blood cell-derived nitric oxide plays. The disease might therefore be treated by more simple and effective methods than those now available to patients through the delivery of nitric oxide to blood cells."

The finding marks the first time that a defect in the ability of patients' red blood cells to process nitric oxide has been linked to a disease, the researchers said. The findings also raise the possibility that defective nitric oxide processing by red blood cells may represent a new class of blood diseases.

Patients with sickle cell disease have an abnormal form of hemoglobin. In the late 1990s, Stamler's team discovered that, in addition to its role in oxygen delivery, hemoglobin acts a biosensor, adjusting blood flow according to the oxygen demand of tissues and organs, by distributing nitric oxide.

Reports by the team in 2001 and 2002 further detailed nitric oxide's role in the red blood cell membrane, confirming it as the third major blood gas, along with oxygen and carbon dioxide. Those findings suggested that nitric oxide defects might play a role in the cardiovascular side effects of many disorders, including diabetes, heart attacks, septic shock and sickle cell disease.

In the current study, the researchers found that hemoglobin in the red cells of patients with sickle cell disease fails to process nitric oxide properly. As a result, they reported, the membranes of sickle red blood cells are deficient for the form of nitric oxide normally released by the cells. The blood cells therefore fail to open blood vessels normally.

Red cells taken from patients with mild sickle cell disease dilate blood vessels under low oxygen conditions, but to a lesser extent than normal red cells. In contrast, red cells from those with severe disease symptoms cause blood vessels to constrict when oxygen levels drop, they found, a response which would further exacerbate the oxygen deficiency. Treatment of red blood cells with nitric oxide reversed that effect, they reported.

"Our results suggest that abnormal blood vessel control by red blood cells contributes to the vessel obstruction characteristic of sickle cell disease, and that variation in symptom severity among patients may be explained, in part, by variable deficiency in the processing of nitric oxide," Stamler said.

In light of the discovery, the researchers call for a re-evaluation of the role that nitric oxide may play in other blood diseases and conditions characterized by a deficiency in oxygen delivery to tissues, such as heart failure, diabetes and pulmonary hypertension.

Collaborators on the study include lead author John Pawloski and Douglas Hess. The work was supported by the National Institutes of Health and a Doris Duke Clinical Scientist Development Award.


Story Source:

The above story is based on materials provided by Duke University Medical Center. Note: Materials may be edited for content and length.


Cite This Page:

Duke University Medical Center. "Discovery Promises Simpler Therapy For Sickle Cell Disease." ScienceDaily. ScienceDaily, 2 February 2005. <www.sciencedaily.com/releases/2005/02/050201104935.htm>.
Duke University Medical Center. (2005, February 2). Discovery Promises Simpler Therapy For Sickle Cell Disease. ScienceDaily. Retrieved October 25, 2014 from www.sciencedaily.com/releases/2005/02/050201104935.htm
Duke University Medical Center. "Discovery Promises Simpler Therapy For Sickle Cell Disease." ScienceDaily. www.sciencedaily.com/releases/2005/02/050201104935.htm (accessed October 25, 2014).

Share This



More Health & Medicine News

Saturday, October 25, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Texas Nurse Nina Pham Cured of Ebola

Texas Nurse Nina Pham Cured of Ebola

AFP (Oct. 25, 2014) — An American nurse who contracted Ebola while caring for a Liberian patient in Texas has been declared free of the virus and will leave the hospital. Duration: 01:01 Video provided by AFP
Powered by NewsLook.com
Toxin-Packed Stem Cells Used To Kill Cancer

Toxin-Packed Stem Cells Used To Kill Cancer

Newsy (Oct. 25, 2014) — A Harvard University Research Team created genetically engineered stem cells that are able to kill cancer cells, while leaving other cells unharmed. Video provided by Newsy
Powered by NewsLook.com
IKEA Desk Converts From Standing to Sitting With One Button

IKEA Desk Converts From Standing to Sitting With One Button

Buzz60 (Oct. 24, 2014) — IKEA is out with a new convertible desk that can convert from a sitting desk to a standing one with just the push of a button. Jen Markham explains. Video provided by Buzz60
Powered by NewsLook.com
Ebola Protective Suits Being Made in China

Ebola Protective Suits Being Made in China

AFP (Oct. 24, 2014) — A factory in China is busy making Ebola protective suits for healthcare workers and others fighting the spread of the virus. Duration: 00:38 Video provided by AFP
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins