• E-mail
• Print
• Comment
• Font Size
• Digg
• del.icio.us
• Discuss article

Researchers Uncover New Clinical Syndrome: Destruction of Red Blood Cells Tied to Severe Symptoms in Diverse Diseases and Conditions

Posted on: Tuesday, 5 April 2005, 18:00 CDT

CHESHIRE, Conn., April 5 /PRNewswire-FirstCall/ -- Researchers have identified a new clinical syndrome that produces serious and sometimes fatal symptoms in a variety of seemingly unrelated diseases. The syndrome, described in the April 6 issue of the Journal of the American Medical Association, is caused by hemolysis, the destruction of red blood cells. The syndrome includes symptoms such as abdominal and swallowing pain, erectile dysfunction, blood clotting and systemic and pulmonary hypertension.

Hemolysis is a critical factor in such conditions as sickle cell disease, paroxysmal nocturnal hemoglobinuria (PNH), malaria, and certain anemias, including those caused by infection, mechanical heart valves and cardiopulmonary bypass. The symptoms caused by hemolysis had not been previously tied together into a single syndrome.

The report was authored by researchers from the National Heart, Lung and Blood Institute of the National Institutes of Health, the Leeds Teaching Hospital NHS Trust, Leeds, UK and Alexion Pharmaceuticals, Inc.

According to the researchers, the syndrome is caused by a novel disease mechanism that begins with the destruction of red blood cells and leads to elevated levels of free hemoglobin in the blood and the subsequent depletion of a key chemical mediator, nitric oxide. Nitric oxide depletion has a profound impact on smooth muscle cells, causing blood vessel constriction, gastrointestinal contractions and cramping, and erectile dysfunction. Nitric oxide is also an important inhibitor of platelet activation and aggregation, and its depletion may play a pivotal role in blood clotting in patients with hemolytic conditions. The researchers reviewed clinical data from volunteers that received hemoglobin preparations as well as from patients with sickle cell disease or PNH, two hemolytic diseases characterized by many of the symptoms of the clinical syndrome.

"This report should raise awareness of physicians from various disciplines of the potential clinical consequences of hemolysis, hemoglobin release and nitric oxide depletion," said Robert Brodsky, M.D., Associate Professor and Director of Hematology, Johns Hopkins University. "The understanding that a common thread likely connects seemingly unrelated conditions further highlights the medical importance of effectively treating hemolysis and its downstream effects."

There are currently no therapies targeted to specifically reduce hemolysis, however, research with an experimental monoclonal antibody, eculizumab, designed to prevent red blood cell destruction in PNH patients, has shown promise. The researchers reported on data published in the New England Journal of Medicine (2004;350:552-559) showing a dramatic reduction in hemolysis in PNH patients. Long-term evaluation of these patients has shown a decrease in symptoms attributed to hemoglobin release and the subsequent depletion of nitric oxide, including abdominal and swallowing pain and erectile dysfunction.

"We are encouraged by the data on eculizumab in the treatment of hemolysis," said Peter Hillmen, MB, Ph.D., Department of Hematology, Leeds Teaching Hospitals NHS Trust Leeds, England and coauthor of the review. "The improvement in patients with PNH following resolution of hemolysis highlights the potential importance of hemoglobin release in the disease process."

The researchers also emphasize the need for intensive ongoing investigation into the link between hemoglobin release, nitric oxide consumption and symptoms of hemolytic disease.

"There are many reasons why nature has chosen to keep hemoglobin hidden inside the red blood cell, but one of the most important is to prevent the removal of nitric oxide from the blood," said Dr. Jack R. Lancaster, Jr., Ph.D., Professor, Center for Free Radical Biology, University of Alabama at Birmingham. "This important report focuses attention on the critical medical implications of this phenomenon and underscores that even small amounts of hemolysis can deplete nitric oxide and disrupt many aspects of normal physiology."

About Alexion Pharmaceuticals

Alexion is engaged in the discovery and development of therapeutic products aimed at treating patients with a wide array of severe disease states, including hematologic and cardiovascular disorders, autoimmune diseases and cancer. Alexion's two lead product candidates, pexelizumab and eculizumab, are currently undergoing evaluation in several clinical development programs, including two Phase III trials of eculizumab for the treatment of paroxysmal nocturnal hemoglobinuria (PNH), a Phase III trial of pexelizumab in coronary artery bypass graft (CABG) surgery patients undergoing cardiopulmonary bypass (CPB), and a Phase III trial of pexelizumab in acute myocardial infarction (AMI) patients. The pexelizumab trials are conducted in collaboration with Procter and Gamble Pharmaceuticals. Under the Special Protocol Assessment process, the FDA has agreed to the design of protocols for the Phase III pexelizumab trials that could, if successful, serve as the primary basis of review for approval of licensing applications for the two indications. Also under the Special Protocol Assessment process, the FDA has agreed to the design of protocols for the two trials of eculizumab in PNH patients that could, if successful, serve as the primary basis of review for approval of a licensing application for eculizumab in the PNH indication. Eculizumab is also being studied in rheumatoid arthritis and membranous nephritis. Alexion is engaged in discovering and developing a pipeline of additional antibody therapeutics targeting severe unmet medical needs, through its wholly owned subsidiary, Alexion Antibody Technologies, Inc. This press release and further information about Alexion Pharmaceuticals, Inc. can be found on the World Wide Web at: http://www.alexionpharm.com/.

This press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. These statements are subject to certain factors which may cause our plans and results to differ significantly from plans and results discussed in such forward-looking statements, including but not limited to the risks discussed in Alexion's Annual Report on Form 10-K for the year ended July 31, 2004 and in our other filings with the Securities and Exchange Commission. Alexion is providing this information as of the date of this press release and does not undertake any obligation to update any forward-looking statement, whether as a result of new information, future events, or otherwise.

Contacts:

Alexion Pharmaceuticals, Inc.

Leonard Bell, M.D.

Chief Executive Officer

(203) 272-2596

Rx Communications

Patricia Garrison (Scientific Media)

(917) 322-2567

Rhonda Chiger (Investors)

(917) 322-2569

Noonan/Russo

Emily Poe (Business and Financial Media)

(212) 845-4266

Alexion Pharmaceuticals

CONTACT: Leonard Bell, M.D., Chief Executive Officer of AlexionPharmaceuticals, Inc., +1-203-272-2596; or Patricia Garrison (ScientificMedia), +1-917-322-2567, or Rhonda Chiger (Investors), +1-917-322-2569, bothof Rx Communications; or Emily Poe (Business and Financial Media) ofNoonan/Russo, +1-212-845-4266

Web site: http://www.alexionpharm.com/

Source: PRNewswire-FirstCall

More News in this Category