Science Current Events | Science News | Brightsurf.com
 

Gene therapy halts pulmonary hypertension progression in large animal pre-clinical study

May 02, 2016

Scientists have used a novel gene therapy to halt the progression of pulmonary hypertension, a form of high blood pressure in the lung blood vessels that is linked to heart failure, according to a study led by Roger J. Hajjar, MD, Professor of Medicine and Director of the Cardiovascular Research Center at the Icahn School of Medicine at Mount Sinai. The study was published online this week, and will appear in the May 3 issue of the Journal of the American College of Cardiology (JACC).

Pulmonary arterial hypertension (PAH) is a rare, rapidly progressing disease that occurs when blood pressure is too high in vessels leading from the heart to the lungs. There is currently no cure for PAH, and about 50 percent of people who are diagnosed will die from the disease within five years. The high pressure is caused by abnormal remodeling of the lung blood vessels that sometimes leads to failure of the right ventricle and premature death. Thickening and narrowing of pulmonary vessels is seen with all types of pulmonary hypertension and is triggered by abnormal calcium levels within the vascular cells. The sarcoplasmic reticulum calcium ATPase pump (SERCA2a) regulates intracellular calcium in vascular cells and prevents them from proliferating in the vessel wall.

"There is considerable need for new treatments that improve functional capacity, symptoms, and survival," said Dr. Hajjar. "This treatment with gene therapy offers a novel method of treating a deadly disease that disproportionately affects young adults and women," he said. Female patients make up about 72 percent of the total population of patients with PAH.

"The therapeutic potential of using gene therapy to treat pulmonary hypertension by delivery of aerosolized adeno-associated virus carrying SERCA2a to directly target vascular remodeling through the overexpression of the SERCA2a protein is very significant," said co-senior study author Jane A. Leopold, MD, of Brigham and Women's Hospital, Harvard Medical School. "In addition, as other novel targets are identified by deep phenotyping of patients with pulmonary hypertension in the National Institutes of Health/National, Heart, Lung, & Blood Institute-funded Pulmonary Vascular Disease Phenomics (PVDOMICS) study, they may be viable candidates for aerosolized gene transfer using adeno-associated viral vectors."

There were two primary objectives for this study, which was conducted by Mount Sinai and research teams from Brigham & Women's Hospital in Boston, MA, and Centro Nacional de Investigaciones Cardiovasculares Carlos III in Madrid, Spain. First, scientists wanted to learn if it is feasible to deliver a therapeutic gene called SERCA2a in aerosol form to damaged blood vessels of the lung using an engineered adeno-associated virus as a "vector." Second, they wanted to see if there was a sustained beneficial impact, and if the transferred genes effectively slowed or stopped the vascular changes in the airways that are the hallmark of PAH and other forms of pulmonary hypertension.

Previously, the novel aerosol inhalation technique used to deliver the SERCA2a gene in this study had proven effective in a rodent model. However, the current study is the first to explore this approach in a large animal--specifically, a Yorkshire swine model that closely resembles PH in humans.

In the study, 20 pigs were divided into two groups, half of which received the aerosolized viral vector carrying the SERCA2a gene and half a saline spray. Two months after the gene delivery, scientists performed tests to see if the new therapeutic genes were present and functioning in the vessels of the animals' lungs, and whether the transfer was producing the desired effects. When they examined the animals, they found that that heart and lung function had improved and abnormal cellular changes causing PH were reduced.

"I'm excited that there is a potential new treatment for patients with this deadly disease," Dr. Hajjar said. "By tailoring the gene therapy, it looks like we can halt the proliferation of smooth muscle cells in the blood vessels. This should help restore function and improve survival in human patients."

Dr. Hajjar said that additional animal studies focusing on long-term efficacy and safety are warranted before advancing this approach, known as airway gene delivery, to human clinical trials. That's because the current study involved a small number of animals, and they were assessed just eight weeks after gene delivery. Nevertheless, he said, airway gene delivery appears to modify fundamental pathophysiology, and therefore might offer therapeutic benefit to humans with a variety of pulmonary vascular diseases.

###

About the Mount Sinai Health System

The Mount Sinai Health System is an integrated health system committed to providing distinguished care, conducting transformative research, and advancing biomedical education. Structured around seven hospital campuses and a single medical school, the Health System has an extensive ambulatory network and a range of inpatient and outpatient services--from community-based facilities to tertiary and quaternary care.

The System includes approximately 6,100 primary and specialty care physicians; 12 joint-venture ambulatory surgery centers; more than 140 ambulatory practices throughout the five boroughs of New York City, Westchester, Long Island, and Florida; and 31 affiliated community health centers. Physicians are affiliated with the renowned Icahn School of Medicine at Mount Sinai, which is ranked among the highest in the nation in National Institutes of Health funding per investigator. The Mount Sinai Hospital is ranked as one of the nation's top 10 hospitals in Geriatrics, Cardiology/Heart Surgery, and Gastroenterology, and is in the top 25 in five other specialties in the 2015-2016 "Best Hospitals" issue of U.S. News & World Report. Mount Sinai's Kravis Children's Hospital also is ranked in seven out of ten pediatric specialties by U.S. News & World Report. The New York Eye and Ear Infirmary of Mount Sinai is ranked 11th nationally for Ophthalmology, while Mount Sinai Beth Israel is ranked regionally.

For more information, visit http://www.mountsinai.org or find Mount Sinai on Facebook, Twitter and YouTube.

The Mount Sinai Hospital / Mount Sinai School of Medicine


Related Pulmonary Hypertension Current Events and Pulmonary Hypertension News Articles


Older patients with atrial fibrillation at greater risk for post-op tricuspid regurgitation after mitral valve repair
Tricuspid regurgitation (TR) occurs when the heart's tricuspid valve leaks, allowing blood to flow back from the right ventricle to the right atrium.

UA College of Pharmacy faculty member develops inhalers to treat lung diseases
Heidi M. Mansour, PhD, assistant professor in the University of Arizona College of Pharmacy, is working to develop advanced dry powder inhalers to treat and prevent pulmonary diseases.

Proliferation of pulmonary endothelial cells is controlled by small RNA fragments
Pulmonary hypertension is an umbrella term used for many conditions that all result in elevation of the pulmonary arterial pressure.

Guidelines first to focus on children with pulmonary hypertension
For the first time, guidelines have been developed for children with pulmonary hypertension, a sometimes fatal heart and lung disease that affects nearly two of every 1,000 babies born each year.

Researchers use brain scans to predict response to antipsychotic medications
Investigators at The Feinstein Institute for Medical Research have discovered that brain scans can be used to predict patients' response to antipsychotic drug treatment. The findings are published online in the latest issue of The American Journal of Psychiatry.

Mass. General team generates therapeutic nitric oxide from air with an electric spark
Treatment with inhaled nitric oxide (NO) has proven to be life saving in newborns, children and adults with several dangerous conditions, but the availability of the treatment has been limited by the size, weight and complexity of equipment needed to administer the gas and the therapy's high price.

UGA researchers find potential treatment for fatal lung diseases
Researchers at the University of Georgia have discovered that the drug triciribine may reverse or halt the progression of pulmonary fibrosis and pulmonary hypertension, two respiratory diseases that are almost invariably fatal.

One in 5 young VTE patients require psychotropic drugs within 5 years
EuroHeartCare is the official annual meeting of the Council on Cardiovascular Nursing and Allied Professions (CCNAP) of the European Society of Cardiology (ESC). The 2015 meeting is held 14 to 15 June in Dubrovnik, Croatia, in collaboration with the Croatian Association of Cardiology Nurses.

Study identifies possible role for carbon monoxide in treating hemorrhagic stroke
Carbon monoxide is known by many as a poisonous gas that causes brain injury and other neurological symptoms, including memory loss and confusion.

Single low-magnitude electric pulse successfully fights inflammation
The Feinstein Institute for Medical Research, the research arm of the North Shore-LIJ Health System, and SetPoint Medical Inc., a biomedical technology company, today released the results of research on the therapeutic potential of vagus nerve stimulation.
More Pulmonary Hypertension Current Events and Pulmonary Hypertension News Articles

Pulmonary Hypertension: Basic Science to Clinical Medicine

Pulmonary Hypertension: Basic Science to Clinical Medicine
by Bradley A. Maron (Editor), Roham T. Zamanian (Editor), Aaron B. Waxman (Editor)


This book provides the framework for a singular reference in the field of pulmonary hypertension. Pulmonary vascular disease is a complex and heterogeneous condition characterized by remodeling of distal pulmonary arterioles that increases pulmonary vascular resistance to affect cardiopulmonary hemodynamic and right ventricular function adversely, resulting in a clinical syndrome of diminished exercise tolerance, shortness of breath, and heart failure-associated morbidity and mortality. Owing to the availability of novel pulmonary circulation-selective pharmacotherapies over the previous decade, the number of pulmonary hypertension patients eligible for treatment has increased substantially. Despite this progress, under-awareness persists within the practicing pulmonary, cardiovascular,...

Pulmonary Hypertension: A Patient's Survival Guide - Fifth Edition, 2013 Revision

Pulmonary Hypertension: A Patient's Survival Guide - Fifth Edition, 2013 Revision
by Pulmonary Hypertension Association


Pulmonary Hypertension: A Patient’s Survival Guide is a a soup-to-nuts guide for pulmonary hypertension (PH) patients and their loved ones that covers topics like the mechanics of PH, the latest treatments, patient care and lifestyle issues. Written by a PH patient for fellow patients, this valuable resource is medically updated every year to keep up with the cutting-edge research and developments in the pulmonary hypertension field.

Author Gail Boyer Hayes wrote the Survival Guide to help answer the questions that a newly diagnosed patient and his or her loved ones may have after leaving the doctor’s office with a PH diagnosis. The book explains the disease process, presently available treatments, and promising new treatments that may be available in the not-too-distant...

Pulmonary hypertension e chart: Full illustrated

Pulmonary hypertension e chart: Full illustrated


Table of Contents
Pulmonary hypertension
Normal pulmonary circulation
Clinical picture 1
Epidemiology 1
Physical exam 2
Prognosis 1
Pathophysiology 1


A  Simple  Guide  To  Pulmonary Artery Hypertension,  Diagnosis, Treatment  And  Related Conditions (A Simple Guide to Medical Conditions)

A Simple Guide To Pulmonary Artery Hypertension, Diagnosis, Treatment And Related Conditions (A Simple Guide to Medical Conditions)


Chapter 1

Pulmonary Artery Hypertension

Pulmonary Arterial Hypertension (PAH) is a rare medical disorder which causes high blood pressure in the arteries to the lungs with no apparent cause.

PAH is also called precapillary pulmonary hypertension or idiopathic pulmonary arterial hypertension (IPAH).

It is a serious condition.

If a person has it, the blood vessels that carry blood from the heart to the lungs become hard and narrow.

In order to pump the blood through, the heart has to work harder.

An overworked heart which becomes weaker over time cannot do its job and the patient can develop heart failure.

IPAH which is not treated will result in right-sided heart failure and death.

Pulmonary hypertension (PH) Miniatlas

Pulmonary hypertension (PH) Miniatlas
by Letbar Asociados S.A.


Pulmonary hypertension is a disease with severe consequences on the quality of life of patients. It is a disorder that may affect individuals of all ages and races, though certain cases have evidenced a genetic predisposition to develop the disease. Initial symptoms are relatively nonspecific, which makes it difficult to establish early diagnosis.As the disease advances, these symptoms which with certain behavioral changes allow leading an acceptable life, become highly disabling. Usual activities that form part of everyday life such as the simple act of walking becomes difficult. The prognosis of pulmonary hypertension is poor, though recent data has indicated that the life expectancy is currently higher than that estimated years ago. Research done over the last few years has attempted...

Pulmonary Hypertension: A Patient's Survival Guide

Pulmonary Hypertension: A Patient's Survival Guide
by Gail Boyer Hayes (Author), Maureen Keane M.S. (Author), Ronald J. Oudiz (Editor)


Brand New Paperback, shrink wrapped, in excellent condition. Ready to ship...(car)

A Simple Guide to Pulmonary Hypertension, Treatment and Related Diseases (A Simple Guide to Medical Conditions)

A Simple Guide to Pulmonary Hypertension, Treatment and Related Diseases (A Simple Guide to Medical Conditions)



Introduction

Ode to Pulmonary Hypertension

Pulmonary hypertension refers to abnormally high pressure
In the pulmonary arteries resulting in right heart failure
Unless treated pulmonary hypertension can be a life-threatening illness.
The fluid in the lung cavity prevents the air to fill the lungs to fullness

Symptoms are often the first clue to pulmonary hypertension
Shortness of breath may be due to the pulmonary congestion
Chest pain and ankle edema indicate evidence of heart failure
Chest x-ray may show enlarged heart and abnormal lung vessels pressure

Pulmonary function tests may be done to look for other lung conditions.
An ECG may be done to record the electrical activity and heart function
Pulmonary Hypertension

Pulmonary Hypertension
by Jim Foster (Editor)


The book consists of overviews and descriptive reviews of several aspects of the clinical presentation, treatment, and pathophysiology of Pulmonary Hypertension (PH), especially pulmonary hypertension associated with thromboembolic disease. Several veteran researchers and expert scientists from across the globe have contributed significant information in this all-inclusive book. The aim of this book is to serve as a good source of reference for researchers, scientists, students, doctors, etc. who are interested in studying about the various aspects of the disease of pulmonary hypertension.

Treatment of Pulmonary Hypertension (Current Cardiovascular Therapy)

Treatment of Pulmonary Hypertension (Current Cardiovascular Therapy)
by Brendan Madden (Editor)


​This title will be presented as highly practical information on pharmaceutical options in pulmonary hypertension, written in a quick-access, no-nonsense format. The emphasis will be on a just-the-facts clinical approach, heavy on tabular material, light on dense prose. The involvement of the ISCP will ensure that the best quality contributors will be involved and establish a consistent approach to each topic in the series. Each volume is designed to be between 100 and 150 pages containing practical illustrations and designed to improve understand and practical usage of cardiovascular drugs in specific clinical areas.​

Diagnosis and Treatment of Pulmonary Hypertension: From Bench to Bedside

Diagnosis and Treatment of Pulmonary Hypertension: From Bench to Bedside
by Yoshihiro Fukumoto (Editor)


This book focuses on pulmonary arterial hypertension (PAH, Group 1) and chronic thromboembolic pulmonary hypertension (CTEPH, Group 4) among the various groups of pulmonary hypertension (PH) whose classification was updated into five major categories at the 5th World Symposium held in Nice, France, in 2013. Readers will find recent progress, methods, and up-to-date information on PH mechanisms, diagnostic images, and treatment in the management of PH.This volume, with contributions by leading researchers worldwide in the field , consists of five parts, starting with the fundamentals of PH, then pathophysiology and genetics, treatment, and right ventricular function.

© 2017 BrightSurf.com