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:6/25/2016)... ... June 25, 2016 , ... As a lifelong Southern Californian, Dr. Omkar Marathe ... from the David Geffen School of Medicine at UCLA. He trained in Internal Medicine ... his fellowship in hematology/oncology at the UCLA-Olive View-Cedars Sinai program where he had the ...
(Date:6/24/2016)... ... June 24, 2016 , ... A recent article ... are unfamiliar with. The article goes on to state that individuals are now more ... these less common operations such as calf and cheek reduction. The Los Angeles area ...
(Date:6/24/2016)... ... June 24, 2016 , ... The Pulmonary Hypertension ... that it will receive two significant new grants to support its work to ... its 25th anniversary by recognizing patients, medical professionals and scientists for their work ...
(Date:6/24/2016)... ... ... of Topricin and MyPainAway Pain Relief Products, join The ‘Business for a Fair Minimum Wage’ ... 2020 and then adjusting it yearly to increase at the same rate as the median ... floor does not erode again, and make future increases more predictable. , The company is ...
(Date:6/24/2016)... ... June 24, 2016 , ... ... Investment Group (TGIG), has initiated cultivation and processing operations at its production facility, ... Pahrump, Nevada. , Puradigm is the manufacturer of a complete system of proactive ...
Breaking Medicine News(10 mins):
(Date:6/23/2016)... Research and Markets has announced ... Type (Organic Chemical (Sugar, Petrochemical, Glycerin), Inorganic Chemical), Functionality ... - Global Forecast to 2021" report to their ... global pharmaceutical excipients market is projected to reach USD ... in the forecast period 2016 to 2021. ...
(Date:6/23/2016)... Research and Markets has announced the addition of the ... to 2022" report to their offering. ... financial data derived from varied research sources to present unique ... on the market during the next five years, including a ... markets, regional and country level analysis. The report provides a ...
(Date:6/23/2016)... 23, 2016 Bracket , a leading clinical ... generation clinical outcomes platform, Bracket eCOA (SM) 6.0, at ... 26 – 30, 2016 in Philadelphia , ... Outcome Assessment product of its kind to fully integrate with ... Bracket eCOA 6.0 is a flexible platform for electronic clinical ...
Breaking Medicine Technology: