Navigation Links
Potential Treatment Found for Debilitating Bone Disease in Wounded Soldiers and Children
Date:4/3/2011

PHILADELPHIA, April 3, 2011 /PRNewswire-USNewswire/ -- Promising new research reveals a potentially highly effective treatment for heterotopic ossification (HO), a painful and often debilitating abnormal buildup of bone tissue. HO comes in two main forms—one that appears in children and is congenital, another that strikes wounded military personnel and surgery patients and is triggered by severe injuries and wounds.

An animal study by developmental biologists shows that a drug that interrupts a signaling-nuclear protein pathway can prevent HO. The study appeared online today in Nature Medicine.

"There are currently no effective treatments for this disease," said study leaders Masahiro Iwamoto, D.D.S., Ph.D., and Maurizio Pacifici, Ph.D., developmental biologists in the Division of Orthopaedic Surgery at The Children's Hospital of Philadelphia. "Surgeons can remove the abnormal bone masses, but surgery itself may trigger more of those growths."

Calling the work an "elegant study," Frederick Kaplan, M.D., said that it "addresses a vast unmet need in clinical medicine." Kaplan, the Isaac & Rose Nassau Professor of Orthopaedic Molecular Medicine at The University of Pennsylvania School of Medicine, who wrote a commentary on the research in the same issue of Nature Medicine, added that the study "provides great hope, insight and direction for the development of effective medications to prevent and treat catastrophic extraskeletal bone formation."

Iwamoto and Pacifici recently came to Children's Hospital from Thomas Jefferson University, where they performed the study. Pacifici holds the new Bong Lee Endowed Chair in Pediatric Orthopaedics at The Children's Hospital of Philadelphia, where he is director of Orthopaedic Research.

The exact mechanism by which HO occurs is not fully understood, but trauma, surgery or deep burns cause local inflammation, followed by the arrival of skeletal cells that develop into chondrocytes (cartilage cells), and are then replaced by intrusive bone. Thus, 10 to 13 percent of orthopedic patients may develop HO, mostly without major symptoms, after knee replacement or other invasive surgeries. The incidence of HO is far higher in wounded soldiers—nearly 65 percent—because modern weapons cause extreme, wide and deep tissue damage.

Although HO is not life-threatening, the bone growths can press against nerves and blood vessels, resulting in chronic pain, limited motion, problems fitting prosthetic limbs and other complications.

The congenital form of the disorder is called fibrodysplasia ossificans progressiva (FOP) and becomes manifest in children by the age of 5 or 6. While very rare, affecting an estimated 700 U.S. children, it is progressive and often fatal in young adults. Surgery cannot be used in children with FOP because it would trigger explosive HO.  

In the current study, Iwamoto and colleagues used retinoid agonists, a class of agents related to vitamin A, in mice that were genetically engineered to model HO. Specifically, they used nuclear retinoic acid receptor-gamma (RAR-gamma) agonists, which selectively target a regulatory pathway during cartilage formation—an essential step in the development of HO.

The RAR-gamma agonists prevented HO from occurring in the mice, with minimal side effects. In contrast, control mice developed HO-like bone masses. Even more encouragingly, the protective effect appeared to be permanent, persisting even after drug treatment ended.

Furthermore, the same agent blocked HO from occurring in mice that had been genetically engineered to express a mutant protein analogous to the one found in children with FOP.

"These agents have the biological properties needed to interfere with the specific events that occur in HO," said Pacifici. "If these animal results are borne out in humans, we may have very potent and effective treatments for both forms of this disease—injury-induced HO and the congenital form."

The authors cautioned that more in-depth preclinical studies must be performed before retinoid agonists are tested in humans with HO. They pointed out, however, that one retinoid agonist is already being used in a current clinical trial for another disease, and it might be possible to gain access to this agent from the manufacturer for clinical trials.

The U.S. Department of the Army and the National Institutes of Health supported this study. Co-authors are from The Children's Hospital of Philadelphia, Thomas Jefferson University College of Medicine, as well as the University of Michigan, Ann Arbor, and Io Therapeutics, Inc., Irvine, California.

"Potent inhibition of heterotopic ossification by nuclear retinoic acid receptor-gamma agonists," Nature Medicine, published online April 3, 2011. doi:10.1038/nm.2334

About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 516-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.

A joint news release from The Children's Hospital of Philadelphia and Thomas Jefferson University John Ascenzi

Rick CushmanThe Children's Hospital of Philadelphia

Thomas Jefferson University 267-426-6055

215-955-2240Ascenzi@email.chop.edu

Richard.Cushman@jefferson.edu
'/>"/>

SOURCE The Children's Hospital of Philadelphia
Copyright©2010 PR Newswire.
All rights reserved

Related biology technology :

1. John Grisham Joins Focused Ultrasound Surgery Foundation Board, Citing Novel Technologys Potential to Help Millions of Patients
2. Self-assembling polymer arrays improve data storage potential
3. Rosetta Genomics and the National Institute of Health (NIH) to Identify Potential MicroRNA Drug Targets for HIV
4. CV Therapeutics Initiates Phase 1 Clinical Trial of CVT-3619, a Novel Potential Treatment for Cardiometabolic Diseases
5. Insmed and Premacure Cite Study Results Demonstrating Potential Effectiveness of IPLEX(TM) in Preventing Blindness in Premature Infants
6. CPC of America, Inc. to Explore Strategic Alternatives; Appoints FTI Capital Advisors to Assess Potential Opportunities
7. Jellyfish Protein Shows Potential to Help With Memory
8. Innovation and Strong Therapeutic Potential Seen in Adult Stem Cells, According to Frost & Sullivan
9. The Medicare Hospital-Acquired Conditions Initiative Will Spur Increased Patient Screening and Potentially Increased Antibiotic Use
10. RVX-208 Exploratory Study Illustrates Early Potential for Alzheimers Disease
11. New Publications Show Noninvasive Magnetic Resonance-Guided Focused Ultrasound to be a Potentially Safe, Effective Pain-Relieving Treatment for Bone Metastases
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:5/25/2016)... (PRWEB) , ... May 25, 2016 , ... Lajollacooks4u has ... and has consistently been rated one of its top attractions. Fortune 500 companies, ... to participate in a unique and intimate team-building experience. , Each event kicks off ...
(Date:5/25/2016)... ... 2016 , ... The Ankle Plating System 3 and Small ... fractures of the distal tibia and fibula. This system marks Acumed's continued commitment ... is composed of seven plate families that span the lateral, medial, and posterior ...
(Date:5/25/2016)... ... May 25, 2016 , ... The American Medical Informatics ... of the National Coordinator for Health IT (ONC) outlining a measurement approach to ... were available when and where it was needed. The organization of health informatics ...
(Date:5/25/2016)... ... May 25, 2016 , ... WEDI, the nation’s leading authority on the ... Charles W. Stellar has been named by the WEDI Board of Directors as WEDI’s ... an executive leader with more than 35 years of experience in healthcare, association management ...
Breaking Biology Technology:
(Date:3/17/2016)... , March 17, 2016 ABI Research, ... forecasts the global biometrics market will reach more ... 118% increase from 2015. Consumer electronics, particularly smartphones, ... fingerprint sensors anticipated to reach two billion shipments ... Dimitrios Pavlakis , Research Analyst at ABI ...
(Date:3/14/2016)... , Allemagne, March 14, 2016 ... http://www.apimages.com ) - --> - Renvoi : ... - --> --> ... solutions biométriques, fournit de nouveaux lecteurs d,empreintes digitales ... LF10 de DERMALOG sera utilisé pour produire des ...
(Date:3/10/2016)... 10, 2016   Unisys Corporation (NYSE: UIS ... (CBP) is testing its biometric identity solution at the ... to help identify certain non-U.S. citizens leaving the country. ... designed to help determine the efficiency and accuracy of using ... and will run until May 2016. --> ...
Breaking Biology News(10 mins):