Navigation Links
Making treatment of rare blood disorder more affordable and effective

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
University of Pennsylvania School of Medicine

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:
(Date:11/27/2015)... , ... November 27, 2015 , ... ... safe and convenient way to dispense prescription medications at home, so he invented ... way to monitor and dispense prescription medications. In doing so, it could help ...
(Date:11/27/2015)... (PRWEB) , ... November 27, 2015 , ... Lizzie’s Lice ... The company is offering customers 10% off of their purchase of lice treatment product. ... at full price. According to a company spokesperson. “Finding lice is a sure way ...
(Date:11/27/2015)... ... November 27, 2015 , ... ProSidebar: Fashion is a set of ... With ProSidebar: Fasion, video editors can easily add an informative sidebar to any FCPX ... Utilize presets featuring self-animating drop zones, lines, bars, and text with the ease ...
(Date:11/27/2015)... ... 2015 , ... Consistent with the Radiology Business Management ... Radiology Marketing Programs meeting will showcase some of the best 2015 radiology ... Palace in Las Vegas with a pre-conference session on a collaborative approach for ...
(Date:11/27/2015)... ... November 27, 2015 , ... A simply groundbreaking television series, "Voices in ... that delves into an array of issues that are presently affecting Americans. Dedicated to ... dialogue, this show is changing the subjects consumers focus on, one episode at a ...
Breaking Medicine News(10 mins):
(Date:11/26/2015)... 26, 2015 ... adds "Global Repaglinide Industry 2015 ... on China Repaglinide Market, 2010-2019" reports ... and information to its online business ... . --> ...
(Date:11/26/2015)... , November 26, 2015 ... of the "Radioimmunoassay Market by Type ... Pharmaceutical Industry, Academics, Clinical Diagnostic Labs), Application ... Forecast to 2020" report to their ... announced the addition of the "Radioimmunoassay ...
(Date:11/25/2015)... , Nov. 26, 2015  The total global healthcare ... 7% over 2015-2016. Latin America has ... , (excluding Japan ), is second ... continues to face increased healthcare expenditure. In 2013-2014, total ... declined from 43.5% in 2008-2009 to 41.2% in 2013-2014. In ...
Breaking Medicine Technology: