Navigation Links
In blood vessel stents, innovative materials allow better control, delivery of gene therapy
Date:4/15/2008

Before gene therapy becomes practical for treating human diseases, researchers must master the details of safe and effective delivery. Cardiology researchers at The Childrens Hospital of Philadelphia have advanced delivery techniques by creating a versatile synthetic material that can bind to a variety of gene therapy vectors and can be custom-designed for controlled local release of therapeutic genes at a disease site.

In an animal study, the research team used their new synthetic formulation to bind adenoviruses to bare metal stents, tiny metal scaffolds inside the carotid arteries of rats. Adenovirus served as a gene therapy vector to carry genes for an enzyme that significantly reduced restenosis, the hazardous narrowing of a blood vessel that often occurs despite the presence of a stent designed to hold it open.

Although the materials are in an early stage, the hope is that this method may help to treat artery disease in people. We developed a synthetic gene delivery system that can be used for any gene therapy vector, not just adenoviruses, said study leader Robert J. Levy, M.D., the William J. Rashkind Chair of Pediatric Cardiology at The Childrens Hospital of Philadelphia. Furthermore, this new formulation allows us to increase the dosage of gene therapy vectors delivered, and we can tune the materials for sustained release over a longer time period.

Levys group reported its study this week in the online version of the journal Circulation, published by the American Heart Association.

Over the past decade, stents have become increasingly useful in treating constricted blood vessels in heart disease and in peripheral artery disease. Stents, which expand partially blocked blood vessels to improve circulation, may be made of bare metal or may have a coating of polymers that release drugs.

Neither type is ideal. Polymer coatings cause inflammation in vessels, which may lead to new bottlenecks at the same time the coating releases drugs meant to reduce vessel injury. Bare metal stents produce less inflammation, but without the benefit of drug delivery. Previously, in a proof-of-principle study in animals, Levys group attached to stents an extremely thin layer of protein, one molecule thick, containing adenovirus vectors that delivered genes that successfully inhibited restenosis. However, that method had serious limitations; it operated only within a narrow range of temperatures and acidity levels, and was useable only with adenovirus vectors.

The new formulation, said Levy, is more robust, more controllable and adaptable to any virus used as a gene therapy vector, not just adenoviruses. His team synthesized three components into a complex that tethers viral vectors to stent surfaces. One of the three components is an amplifier that increases the dose of gene vector more than fourfold over the previous formulation.

In addition, by varying another component, the stent can be tuned to release vector at a controlled rate that can theoretically be tailored to a schedule appropriate for the particular treatment. Prior studies have shown that 90 percent of the gene vector is released within 12 to 24 hours, after which vessel blockages regrow, said Levy. In this study, the stents had significant coverage of the vector seven days laterand less restenosis. Our goal is to customize the materials to allow peak release of the vector when it can have the maximum benefit.

The adenovirus vector carries genes that code for inducible nitric oxide synthase (iNOS), a protein that controls cell damage in blood vessels. In the current study, the iNOS reduced restenosis by 56 percent in the carotid arteries of treated rats, as compared with control animals.

Although this particular study used adenovirus vectors, said Levy, the synthetic formulation could tether any other type of viral gene therapy vector to the metal stents. It might also carry other therapeutic agents in addition to gene vectors. Further studies, he added, will refine these methods and investigate them in larger animal models that more closely simulate human vessel disease.


'/>"/>

Contact: John Ascenzi
Ascenzi@email.chop.edu
267-426-6055
Children's Hospital of Philadelphia
Source:Eurekalert

Related medicine news :

1. Mediware Introduces Comprehensive Vision for Blood Center Technology
2. High Blood Pressure May Be Buffer Against Headaches
3. Potential blood test for chronic sinusitis identified
4. Blood pressure drugs halt pancreatic cancer cell growth, Jefferson researchers find
5. Abbott FreeStyle Freedom(R) Lite Blood Glucose Monitoring System Now Available With No Coding for People With Diabetes
6. PATHFAST(R): Rapid Whole Blood Immunoassay Analyzer from Polymedco
7. Blood vessels: The pied piper for growing nerve cells
8. Cholesterol, blood pressure control may reverse atherosclerosis in adults with diabetes
9. Aggressive Cholesterol, Blood Pressure Treatment Shows Some Benefit
10. Microwave treatments for enlarged prostate cause blood pressure surges
11. Blood pressure enzyme can have tumor-sensing role
Post Your Comments:
*Name:
*Comment:
*Email:
(Date:10/13/2017)... ... October 13, 2017 , ... The International Association of ... of excellence for the field of eating disorders, announces the opening of early ... in Orlando, Florida at the Omni Resort at ChampionsGate. , The ...
(Date:10/13/2017)... Shelton, CT (PRWEB) , ... October 13, 2017 , ... ... and long-term care services, staged a mock evacuation of the facility as part of ... Department, Shelton Fire Department, Echo Hose EMS and Shelton City Emergency Manager, as well ...
(Date:10/13/2017)... ... ... Global Healthcare Management’s 4th Annual Kids Fun Run brought out many kids ... sponsored by Global Healthcare Management’s CEO, Jon Letko, is aimed at getting kids excited ... all ages; it is a non-competitive, non-timed event, which is all about having fun ...
(Date:10/13/2017)... ... ... Journey: From the Mountains to the Mission Field”: the story of a missionary couple ... From the Mountains to the Mission Field” is the creation of published author, Carole ... and currently teaches a class of ladies at her church, which she has taught ...
(Date:10/12/2017)... , ... October 12, 2017 , ... Planet Fitness, one ... U.S., announced today its plans to open a flagship location in Covington, LA at ... former Rooms To Go store next to Office Depot in the Holiday Square shopping ...
Breaking Medicine News(10 mins):
(Date:10/12/2017)... AVACEN Medical , Inc. (AVACEN) announced that Frost & ... Innovation Award for Its fibromyalgia pain management device. The ... market research by Frost & Sullivan,s industry experts. ... product, the AVACEN 100, offers a safe and effective solution ... ...
(Date:10/11/2017)...  Caris Life Sciences ® , a leading innovator ... precision medicine, today announced that St. Jude Medical Center,s ... (POA) as its 17 th member. Through participation ... Cancer Institute will help develop standards of care and ... making cancer treatment more precise and effective. ...
(Date:10/10/2017)... 2017   West Pharmaceutical Services, Inc. (NYSE: ... drug administration, today shared the results of a study ... the intradermal administration of polio vaccines. The study results ... May 2017 by Dr. Ondrej Mach , Clinical ... Organization (WHO), and recently published in the journal ...
Breaking Medicine Technology: