Navigation Links
Making treatment of rare blood disorder more affordable and effective
Date:2/27/2014

PHILADELPHIA A University of Pennsylvania research team has defined a possible new way to fight a disease that is currently treatable only with the most expensive drug available for sale in the United States. In a study published this month in Blood, the Penn team describes the strategy, based on the oldest part of the human immune system called "complement" -- that could turn out to be less costly and more effective for the majority of patients with a rare blood disorder.

Complement is a network of more than 50 proteins in the blood and on cell surfaces that quietly cruise the body, keeping a low profile until triggered into action. On the other hand, this system can turn, contributing to a broad spectrum of immune, inflammatory, and age-related diseases.

John Lambris, PhD, the Dr. Ralph and Sallie Weaver Professor of Research Medicine in the Department of Pathology and Laboratory Medicine in the Perelman School of Medicine, studies this early-warning system and how to correct it when its response goes overboard.

This is known to be the case with paroxysmal nocturnal hemoglobinuria (PNH), a rare but life-threatening hematological disorder, which is estimated to affect between 1 and 5 per million people. In PNH, defective expression of regulatory proteins on the surface of blood cells leaves them vulnerable to complement attack. This can lead to premature death of the red blood cells, a process called hemolysis, which clinically results in severe anemia and contributes to a high risk of clotting.

Lambris and Daniel Ricklin, PhD, research assistant professor of Pathology and Laboratory Medicine, are developing novel therapeutics to tame this inappropriate complement activation and protect cell surfaces from attack.

Eculizumab (Soliris, an Alexion Pharmaceuticals drug) -- to date the only approved therapeutic for PNH -- reduces hemolysis and gives relief from blood transfusions for most PNH patients. However, Eculizumab is costly (currently the most expensive drug used in the US at more than $400,000 per year per patient), and one third of PNH patients continue to require blood transfusions to manage their anemia. As first described by co-author Antonio Risitano, MD, at the University of Naples in Italy, this non-response is due to fragments of complement C3 proteins on the surface of their red blood cells, which are eventually attacked by immune cells.

Lambris and colleagues have thought that inhibition of the "complement cascade" at the level of C3 proteins using small inhibitory molecules might be a superior strategy as it prevents both hemolysis and immune cell recognition while being potentially more cost-effective when compared to the current antibody-based treatment.

The team investigated the effect of a C3 inhibitor called Cp40 and its long-acting form PEG-Cp40 on self attack and resulting hemolysis using human PNH cells. Both compounds demonstrated inhibition of hemolysis and efficiently prevented deposition of C3 fragments on PNH red blood cells. In non-human primates, a single injection of PEG-Cp40 into the blood stream resulted in a longer time that the drug stayed in circulation, a property important for drug development.

"We think these two compounds are excellent and potentially cost-effective candidates for further clinical investigation," says Lambris, who hopes that the compounds could be tested in clinical trials by 2015.


'/>"/>

Contact: Karen Kreeger
karen.kreeger@uphs.upenn.edu
215-349-5658
University of Pennsylvania School of Medicine
Source:Eurekalert

Related medicine news :

1. Brain Changes May Hamper Decision-Making in Old Age
2. OHSU Oregon National Primate Research Center develops new, safer method for making vaccines
3. After 25 years, World No Tobacco Day is making an impact
4. Making bad worse for expectant mothers
5. DotComSecrets’ Russell Brunson Is Revealing Online Money Making Secrets in Free Webinars for Students
6. New Electronic Cigarette Free Trial Kit Adds More Years to Smokers Life by Making it Easy to Quit Smoking
7. First Is Viewed as Best When Making Quick Decisions
8. Neuroeconomics to study decision-making in anxious individuals
9. Making it easier to learn to read
10. The making and unmaking of stem-like, aggressive breast cancer cells
11. UH students spent summer making a difference with hands-on research
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:3/23/2017)... New York, NY (PRWEB) , ... March 23, 2017 , ... 82% of adults are ... every 3 kids do not brush their teeth the minimum two times a day that ... teeth; with students missing 51 million hours of school and adults missing 164 million hours ...
(Date:3/23/2017)... Los Angeles, CA (PRWEB) , ... March 23, ... ... Series A funding investment in Los Angeles based healthcare technology company California Healthcom ... group’s portfolio into the US, and healthcare arena. With headquarters in California, CHG ...
(Date:3/23/2017)... ... 2017 , ... After raising more than $1.135 million ($1,479,231 AUD) from nearly ... in crowdfunding history, has established a U.S. Headquarters in New York City, FaceCradle ... , “We’re excited to be operating on U.S. shores, where most of our initial ...
(Date:3/23/2017)... ... 23, 2017 , ... According to the National Sleep Foundation , poor ... the only cause of the sunken-eye look, which can include dark circles or bags ... poor health are likely due to genetics, dehydration, allergies, and losing fat beneath the ...
(Date:3/23/2017)... ... March 23, 2017 , ... The American Board of Quality Assurance ... Anniversary of ABQAURP’s dedication to Health Care Quality and Management and Patient Safety. , ... only to the association, but also to the Health Care Quality and Patient Safety ...
Breaking Medicine News(10 mins):
(Date:3/23/2017)... VANCOUVER, British Columbia , March 23, 2017 /PRNewswire/ ... "Company" or "Sophiris"), a clinical late-stage biopharmaceutical company developing ... announced that data from its successful Phase 2a study ... treatment for localized prostate cancer, will be presented as ... nd Annual European Association of Urology in ...
(Date:3/23/2017)... 2017  Ethicon* today announced the completion of ... held medical device company that manufactures and markets ... treatment of Gastroesophageal Reflux Disease (GERD). This acquisition ... portfolio of minimally invasive options for patients suffering ... of the transaction have not been disclosed. ...
(Date:3/23/2017)... LITTLE SILVER, N.J. , March 23, 2017 ... device company, today announced that it has kicked ... in-growth into their 3D printed bone segments. ... of Engineering, "Our unique variable honeycomb lattice structures ... bone in-growth as compared to current allograft wedges ...
Breaking Medicine Technology: