Navigation Links
Researchers develop gene therapy to reverse pulmonary arterial hypertension

A University of Alberta research team has discovered important new information they hope will lead to more effective treatments for pulmonary arterial hypertension (PAH)--a deadly form of high blood pressure in the pulmonary arteries caused by uncontrolled cell growth. Therapies are currently limited for a disease that can lead to heart failure and death within a few years.

The researchers have shown that Survivin, a protein almost exclusively expressed in cancer, is also heavily expressed in both human and animal lung arteries with PAH. Survivin is an inhibitor of apoptosis--or programmed cell death--which promotes cancer by suppressing the body's ability to limit excessive cell growth.

Armed with this new information and using animal models, the researchers developed a nebulized and inhaled gene therapy to deliver an inactive Survivin-mutant via a virus--known in science as a "dominant negative construct"--effectively inhibiting endogenous Survivin. The therapy reversed PAH in rats and improved their heart function and their survival, thus holding out some promising avenues of treatment for human PAH. The team members believe that as in cancer, Survivin drives excessive cell growth in the PAH lung blood vessels.

"The most intriguing aspect," explains principal researcher Evangelos Michelakis, "is we've shown for the first time that this cancer protein is also expressed within the blood vessels of the lung in patients suffering with PAH, but not in normal human blood vessels, making survivin a very attractive target for selective intervention.

"This makes the proliferation of lung blood vessels in this disease a 'form of cancer' or a form of neoplasia to be more precise, first proposed by Drs. Voelkel and Tuder from the University of Colorado. We've demonstrated for the first time that, like cancer, apoptosis is suppressed in the lung blood vessel wall in this disease."

"Our biggest challenge in treating PAH is the fact we don 't know what makes the cells in the lung blood vessel wall grow excessively," says the University of Alberta cardiology professor and Canada Research Chair holder. "And therapies also have to target the lung blood vessels and spare the normal cells in the rest of the body."

The paper is entitled Gene therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. It's published in the June issue of The Journal of Clinical Investigation. In an accompanying editorial entitled Lessons learned from cancer may help in the treatment of pulmonary hypertension, written by French researcher Serge Adnot, the journal stated: "These findings raise important issues regarding the role of survivin in the pathogenesis of PAH, its value as a prognostic indicator, and its use as a target for new therapeutic strategies."

Other authors include: Sean McMurtry, Pulmonary Hypertension Program; Stephen Archer, Canada Research Chair in Translational Cardiovascular Research; Dario Altieri, Department of Cancer Biology and the Cancer Center, University of Massachusetts Medical School; Sebastien Bonnet, Alois Haromy, Gwyneth Harry and Sandra Bonnet, the Vascular Biology Group and Pulmonary Hypertension Program; and Lakshmi Puttagunta, Department of Laboratory Medicine and Pathology, U of A.

The latest research builds on previous work by the group, published a few months ago in Circulation Research, showing that an orally available drug, Dichloroacetate, selectively enhances apoptosis in PAH and thus reverses PAH, prolonging the survival of rats. Because this oral therapy has already been tried in humans with congenital mitochondrial diseases, the team is initiating a clinical trial in human PAH. Similarly, newer drugs that inhibit Survivin, currently in trials in oncology, might also be directly applicable to PAH patients, Dr. Michelakis explains.

The researchers are supported by the Canadian Institutes o f Health Research and Canada Research Chair Program, the Alberta Heart and Stroke Foundation, the Alberta Heritage Foundation for Medical Research, the Canadian Institutes of Health Research, the National Institutes of Health, and the Alberta Cardiovascular and Stroke Research Centre (ABACUS). Dr. McMurtry is supported by the University's clinician investigator program and TORCH, a CIHR-sponsored multidisciplinary training program in cardiovascular disease, and a training grant from Bristol-Myers Squibb Company.


'"/>

Source:University of Alberta


Related biology news :

1. Researchers discover way to make cells in the eye sensitive to light
2. Researchers find how protein allows insects to detect and respond to pheromones
3. Researchers Uncover Key Step In Manufacture of Memory Protein
4. Researchers reveal the infectious impact of salmon farms on wild salmon
5. Researchers identify target for cancer drugs
6. Researchers discover molecule that causes secondary stroke
7. Researchers find missing genes of ancient organism
8. Researchers trace evolution to relatively simple genetic changes
9. Researchers add new tool to tumor-treatment arsenal
10. UF Researchers Map Bacterial Proteins That Cause Tooth Loss
11. VCU Researchers Identify Networks Of Genes Responding To Alcohol In The Brain
Post Your Comments:
*Name:
*Comment:
*Email:


(Date:6/22/2016)... BETHESDA, Md. , June 22, 2016  The American ... by Trade Show Executive Magazine as one of ... Summit on May 25-27 at the Bellagio in ... based on the highest percentage of growth in each of ... number of exhibiting companies and number of attendees. The 2015 ...
(Date:6/20/2016)... 20, 2016 Securus Technologies, a leading ... for public safety, investigation, corrections and monitoring announced ... it has secured the final acceptance by all ... Managed Access Systems (MAS) installed. Furthermore, Securus will ... be installed by October, 2016. MAS distinguishes between ...
(Date:6/9/2016)... , June 9, 2016 ... deploy Teleste,s video security solution to ensure the safety of ... during the major tournament Teleste, an ... systems and services, announced today that its video security solution ... to back up public safety across the country. The ...
Breaking Biology News(10 mins):
(Date:6/27/2016)...  Liquid Biotech USA , ... Sponsored Research Agreement with The University of Pennsylvania ... cancer patients.  The funding will be used to ... clinical outcomes in cancer patients undergoing a variety ... employed to support the design of a therapeutic, ...
(Date:6/24/2016)... June 24, 2016  Regular discussions on a range of ... between the two entities said Poloz. Speaking at ... Ottawa , he pointed to the country,s inflation target, ... government. "In certain ... institutions have common economic goals, why not sit down and ...
(Date:6/24/2016)... ... June 24, 2016 , ... While the majority of commercial spectrophotometers and ... and the 6000i models are higher end machines that use the more unconventional z-dimension ... light beam from the bottom of the cuvette holder. , FireflySci has developed ...
(Date:6/23/2016)... ... 23, 2016 , ... Mosio, a leader in clinical research ... Recruitment and Retention Tips.” Partnering with experienced clinical research professionals, Mosio revisits the ... tools, and strategies for clinical researchers. , “The landscape of how patients receive ...
Breaking Biology Technology: