For the first time scientists have found an antibody treatment that not only stops PAH getting worse, but also reverses the condition in mice and rats. The research was funded by the British Heart Foundation and the Medical Research Council (MRC) and is published in the Journal of Experimental Medicine.
PAH – high pressure in the blood vessels supplying the lungs – is a devastating condition that affects almost 2,200 adults in England and Wales. It is caused by changes in the cells lining the arteries that take blood from the heart to the lungs (a process called vascular remodelling).
Vascular remodelling causes the walls of the vessels to become stiff and thickened making it harder for blood to flow through them, which in turn causes an elevation in blood pressure. This increased pressure places significant strain on the right side of the heart, which can lead to fatal heart failure if left untreated. PAH often affects young people, and more commonly women.
Current treatments for PAH target the constriction of the arteries, but fail to fully reverse the underlying vascular remodelling. The researchers demonstrated that a protein called TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) worsened the progression of PAH in animal models, but blocking TRAIL with an antibody improved the disease.
Dr Allan Lawrie, a MRC Career Development Fellow from the University of Sheffield's Department of Cardiovascular Science, who led the study, said: "This research opens up a new insight into the mechanisms of PAH and suggests that TRAIL is critical to this process. If we can interrupt this process by blocking the TRAIL pathway, we have the potential to stop the disease in its tracks and even reverse the damage already done."
Since the discovery of TRAIL and its network of receptors, the majority of attention has focused on the clinical potential of manipulating this pathway in cancer therapy. However new research suggests that TRAIL plays broader roles in regulating immune processes, with this latest study suggesting it is critical to PAH.
"These data, from animal models, provide validation and we are now actively pursuing a route to develop human antibodies as a potential new treatment for PAH, though this is likely to be several years from the clinic," said Dr Lawrie.
Dr Shannon Amoils, Research Advisor at the British Heart Foundation (BHF), which co-funded the study, said:
"We urgently need to find new treatments for people with pulmonary arterial hypertension, a condition which can have a devastating effect on people's quality of life and is often fatal. This study shows that a protein called TRAIL plays a role in the disease by driving the overproduction of cells lining the lungs' blood vessels. This overproduction of cells is one of the factors leading to high blood pressure in the lungs."Importantly, the researchers show that in rodents, blocking TRAIL using an antibody dampens down this high cell turnover and reduces the disease severity. There is still a long way to go, but the hope is that the TRAIL antibody might be developed into a new treatment for patients in the future."
Notes for Editors
Medical Research CouncilFor almost 100 years the Medical Research Council has improved the health of people in the UK and around the world by supporting the highest quality science. The MRC invests in world-class scientists. It has produced 29 Nobel Prize winners and sustains a flourishing environment for internationally recognised research. The MRC focuses on making an impact and provides the financial muscle and scientific expertise behind medical breakthroughs, including one of the first antibiotics penicillin, the structure of DNA and the lethal link between smoking and cancer. Today MRC funded scientists tackle research into the major health challenges of the 21st century. www.mrc.ac.uk
For more information visit: www.bhf.org.uk/pressoffice.
For further information please contact: Amy Pullan, Media Relations Officer, on 0114 222 9859 or email firstname.lastname@example.org
To read other news releases about the University of Sheffield, visit: http://www.shef.ac.uk/news
Amy Pullan | EurekAlert!
Speed data for the brain’s navigation system
06.12.2016 | Deutsches Zentrum für Neurodegenerative Erkrankungen e.V. (DZNE)
Study suggests possible new target for treating and preventing Alzheimer's
02.12.2016 | Oregon Health & Science University
In recent years, lasers with ultrashort pulses (USP) down to the femtosecond range have become established on an industrial scale. They could advance some applications with the much-lauded “cold ablation” – if that meant they would then achieve more throughput. A new generation of process engineering that will address this issue in particular will be discussed at the “4th UKP Workshop – Ultrafast Laser Technology” in April 2017.
Even back in the 1990s, scientists were comparing materials processing with nanosecond, picosecond and femtosesecond pulses. The result was surprising:...
Have you ever wondered how you see the world? Vision is about photons of light, which are packets of energy, interacting with the atoms or molecules in what...
A multi-institutional research collaboration has created a novel approach for fabricating three-dimensional micro-optics through the shape-defined formation of porous silicon (PSi), with broad impacts in integrated optoelectronics, imaging, and photovoltaics.
Working with colleagues at Stanford and The Dow Chemical Company, researchers at the University of Illinois at Urbana-Champaign fabricated 3-D birefringent...
In experiments with magnetic atoms conducted at extremely low temperatures, scientists have demonstrated a unique phase of matter: The atoms form a new type of quantum liquid or quantum droplet state. These so called quantum droplets may preserve their form in absence of external confinement because of quantum effects. The joint team of experimental physicists from Innsbruck and theoretical physicists from Hannover report on their findings in the journal Physical Review X.
“Our Quantum droplets are in the gas phase but they still drop like a rock,” explains experimental physicist Francesca Ferlaino when talking about the...
The Max Planck Institute for Physics (MPP) is opening up a new research field. A workshop from November 21 - 22, 2016 will mark the start of activities for an innovative axion experiment. Axions are still only purely hypothetical particles. Their detection could solve two fundamental problems in particle physics: What dark matter consists of and why it has not yet been possible to directly observe a CP violation for the strong interaction.
The “MADMAX” project is the MPP’s commitment to axion research. Axions are so far only a theoretical prediction and are difficult to detect: on the one hand,...
16.11.2016 | Event News
01.11.2016 | Event News
14.10.2016 | Event News
06.12.2016 | Power and Electrical Engineering
06.12.2016 | Earth Sciences
06.12.2016 | Physics and Astronomy