Corporate Banner
Satellite Banner
Genomics
Scientific Community
 
Become a Member | Sign in
Home>News>This Article
  News
Return

Common Childhood Asthma Not Rooted in Allergens, Inflammation

Published: Friday, May 24, 2013
Last Updated: Friday, May 24, 2013
Bookmark and Share
Discovery of origins of a unique form of asthma may lead to a precision medicine approach to treatment.

Little is known about why asthma develops, how it constricts the airway or why response to treatments varies between patients. Now, a team of researchers at Weill Cornell Medical College, Columbia University Medical Center and SUNY Downstate Medical Center has revealed the roots of a common type of childhood asthma, showing that it is very different from other asthma cases.

Their report, in Science Translational Medicine, reveals that an over-active gene linked in 20 to 30 percent of patients with childhood asthma interrupts the synthesis of lipid molecules (known as sphingolipids) that are part of cell membranes found all over the body.

Although the researchers do not yet understand why asthma results from reduced production of sphingolipids, their experiments clearly show a link between loss of these lipids and bronchial hyperreactivity, a key feature of asthma.

What makes this pathway unique, investigators say, is that it is not related to allergens and, the investigators discovered, has nothing to do with inflammation.

“Usually asthma is thought to be an inflammatory disease or a reaction to an allergen. Our model shows that asthma can result from having too little of a type of sphingolipids. This is a completely new pathway for asthma pathogenesis,” says the study’s senior author, Dr. Stefan Worgall, chief of the Pediatric Pulmonology, Allergy and Immunology Division at NewYork-Presbyterian Hospital/Weill Cornell Medical Center.

This is very good news, he adds. “Our findings are not only valuable in understanding the pathogenesis of this complex disease, but provide a basis to develop novel therapies, especially asthma agents based on a patient’s genotype,” says Dr. Worgall, who is also a distinguished professor of pediatric pulmonology, professor of pediatrics and associate professor of genetic medicine at Weill Cornell Medical College.

Precision Medicine for Asthma

Asthma is a significant health problem affecting about 7 million children in the United States. Nearly 10 percent of American children 0–17 years of age have asthma, making it the most common serious respiratory childhood disease. Its prevalence is even higher among inner-city children, says Dr. Worgall. Besides causing suffering, disability and alarm, the economic toll is significant, he says: In 2009, asthma caused 640,000 emergency room visits and 157,000 hospitalizations, plus 10.5 million missed school days.

“Yet while it has become increasingly evident that asthma takes several forms, treatment of the disorder is uniform,” he says. “Most therapies are designed to reduce inflammation, but they do not help all sufferers.”

The notion that asthma has different forms gained ground after several genome-wide association studies (GWAS) found variation in a gene, later identified as ORMDL3, in to up to 30 percent of asthma cases. In 2007, over-production of the gene’s protein was connected to childhood asthma, and this gene has been the most consistent genetic factor identified so far for asthma.

In 2010, a study in yeast found that ORMDL3 protein inhibits sphingolipid de-novo synthesis.

This finding prompted the researchers to investigate whether sphingolipid production is connected to asthma. Their study shows that this is indeed true in mouse models of the disease. Using mouse models, the researchers found that inhibition of an enzyme, serine palmitoyl-CoA transferase (SPT), which is critical to sphingolipid synthesis, produced asthma in mice and in human airways, as it did in mice that had a genetic defect in SPT.

The airway hyperactivity seen in the mice was not linked to increased inflammation, and the scientists saw a decreased response of the lung and airways to magnesium — which is often used in emergency rooms to relieve chest tightness of patients with asthma attacks.

“In our mouse models, we found that magnesium was not effective at inducing airway relaxation, suggesting the same would be true for humans whose asthma is linked to ORMDL3,” says the study’s first author, Dr. Tilla S. Worgall, assistant professor in the Department of Pathology and Cell Biology and a member of the Institute of Human Nutrition at Columbia University Medical Center. “The association of decreased de novo sphingolipid synthesis with alterations in cellular magnesium homeostasis provides a clue into the mechanism of asthma. Therefore, therapies that circumvent the effect of the ORMDL3 genotype may be effective treatments for asthma sufferers. We are now working towards developing these new therapies.”

The paper is titled, “Impaired sphingolipid synthesis in the respiratory tract induces airway hyperreactivity.” Additional authors include Arul Veerappan, Biin Sung, Evan Weiner, Rheeshma Bholah and Dr. Randy B. Silverfrom Weill Cornell Medical College; Benjamin I. Kimfrom Columbia University Medical Center; and Dr. Xian-Cheng Jiang from SUNY Downstate Medical Center (formally known as The State University of New York at Brooklyn).


Further Information

Join For Free

Access to this exclusive content is for Technology Networks Premium members only.

Join Technology Networks Premium for free access to:

  • Exclusive articles
  • Presentations from international conferences
  • Over 3,200+ scientific posters on ePosters
  • More than 4,600+ scientific videos on LabTube
  • 35 community eNewsletters


Sign In



Forgotten your details? Click Here
If you are not a member you can join here

*Please note: By logging into TechnologyNetworks.com you agree to accept the use of cookies. To find out more about the cookies we use and how to delete them, see our privacy policy.

Related Content

New Neurodevelopmental Syndrome Identified
Study pinpoints underlying genetic mutations, raising hopes for targeted therapies.
Friday, April 22, 2016
New Link Between Obesity and Diabetes Found
Targeting a single enzyme that raises both sugar and insulin levels in the obese could prevent and treat diabetes.
Monday, November 25, 2013
Is There a Role for Vitamins in Cancer Prevention?
According to recent national surveys, approximately 40 percent of U.S. adults take multivitamins/multiminerals.
Monday, August 12, 2013
Study Reveals Genes That Drive Brain Cancer
About 15 percent of glioblastoma patients could receive personalized treatment with drugs currently used in other cancers.
Tuesday, August 06, 2013
Key Molecular Pathways Leading to Alzheimer’s Identified
Research approach highlights potential therapeutic targets.
Thursday, July 25, 2013
New Genetic Cause of Pulmonary Hypertension Identified
Study finds druggable target for rare fatal lung disease.
Thursday, July 25, 2013
Mutation Linked to Congenital Urinary Tract Defects
Findings point to new diagnostic category.
Thursday, July 18, 2013
Mouse Study Suggests Lead May Trigger Schizophrenia
Behavioral and MRI study in mice points to a synergistic relationship between lead exposure and schizophrenia gene.
Monday, June 10, 2013
Many Birth Defects in Heart Caused by Spontaneous Mutations
A study has found that at least 10 percent of cases stem from genetic mutations that occur spontaneously early in development.
Thursday, May 30, 2013
Looking for the Telltale Gene
A new genetic test allows parents to peer into their unborn children's medical future.
Friday, May 24, 2013
Hundreds of Alterations and Potential Drug Targets to Starve Tumors Identified
A massive study analyzing gene expression data from 22 tumor types has identified multiple metabolic expression changes associated with cancer.
Monday, April 22, 2013
New Gene Associated with Almost Doubled Alzheimer’s Risk in African-Americans
ABCA7, a minor gene variant in whites, is major player in African-Americans.
Wednesday, April 10, 2013
Schizophrenia Gene Networks Found, and a Link to Autism
Although schizophrenia is highly genetic in origin, the genes involved in the disorder have been difficult to identify.
Thursday, November 15, 2012
New de novo Genetic Mutations in Schizophrenia Identified
Columbia University Medical Center (CUMC) researchers have identified dozens of new spontaneous genetic mutations that play a significant role in the development of schizophrenia, adding to the growing list of genetic variants that can contribute to the disease.
Thursday, October 04, 2012
New de novo Genetic Mutations in Schizophrenia Identified
Columbia University Medical Center (CUMC) researchers have identified dozens of new spontaneous genetic mutations that play a significant role in the development of schizophrenia, adding to the growing list of genetic variants that can contribute to the disease.
Thursday, October 04, 2012
Scientific News
Benchtop Automation Trends
Gain a better understanding of current interest in and future deployment of benchtop automated systems.
Higher Frequency of Huntington's Disease Mutations Discovered
University of Aberdeen study shows that the gene change that causes Huntington's disease is much more common than previously thought.
Revealing the Genetic Causes of Bowel Cancer
A landmark study has given the most detailed picture yet of the genetics of bowel cancer — the UK's fourth most common cancer.
The Epigenetic Influences of Chronic Pain
Researchers at Drexel University College of Medicine are aiming to identify new molecular mechanisms involved in pain.
Fighting Resistant Blood Cancer Cells
Biologists present new findings on chronic myeloid leukemia and possible therapeutic approaches.
Tumor Cells Develop Predictable Characteristics
Scientists have discovered that cancer cells at the edge of a tumor that are close to the surrounding environment are predictably different from the cells within the interior of the tumor.
Mothers Obesity Could be Passed on in mtDNA
Obesity can predispose offspring in multiple generations to metabolic problems.
New Imaging Method Reveals Nanoscale Details about DNA
Enhancement to super-resolution microscopy shows orientation of individual molecules, providing a new window into DNA’s structure and dynamics.
Genetic Research Can Significantly Improve Drug Development
With drug development costs topping $1.2bn (£850 million) to get a single treatment to the point it can be sold and used in the clinic, could genetic analysis save hundreds of millions of dollars?
Naked Mole Rat Exhibits “Extraordinary” Cancer Resistance
Scientists are getting closer to understanding the anti-cancer mechanism of the naked mole rat by making induced pluripotent stem cells.
Skyscraper Banner

SELECTBIO Market Reports
Go to LabTube
Go to eposters
 
Access to the latest scientific news
Exclusive articles
Upload and share your posters on ePosters
Latest presentations and webinars
View a library of 1,800+ scientific and medical posters
3,200+ scientific and medical posters
A library of 2,500+ scientific videos on LabTube
4,600+ scientific videos
Close
Premium CrownJOIN TECHNOLOGY NETWORKS PREMIUM FOR FREE!