Hopkins Researchers Find Drug May Help Cystic Fibrosis Patients

November 17, 1997

Researchers at the Johns Hopkins Children's Center have found that a drug used to normalize blood ammonia levels also holds promise for cystic fibrosis.

People with cystic fibrosis have mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, which normally codes for a protein that transports chloride across the cell membrane. Approximately 70% of cystic fibrosis patients have the same mutation (called the deltaF508 mutation) in this gene, which results in a protein that is partly functional but that rarely gets transported to the surface of the cell. Instead, these CFTR proteins become "stuck" on the way to the surface and are degraded. Consequently, little or no chloride can be transported across the cell membrane. In cystic fibrosis, this chloride imbalance results in a thick mucus that causes recurrent airway and intestinal obstructions, as well as chronic respiratory infections.

The addition of sodium 4-phenylbutyrate (4PBA) to cells with the deltaF508 mutation allows more CFTR proteins to reach cell surfaces, where they can transport chloride, according to Ronald C. Rubenstein, M.D., Ph.D., an instructor in pediatrics at Hopkins and lead author of the study. This phenomenon occurs at concentrations of 4PBA normally seen in patients who already take the drug for urea cycle disorders, which are genetic diseases characterized by high levels of ammonia in the bloodstream.

The study appears in the November 15 issue of the Journal of Clinical Investigation.

"A therapy directed at correcting the abnormal intracellular transport of the deltaF508 mutation is potentially beneficial to the majority of CF patients," says Rubenstein. "We are very encouraged by 4PBA's apparent action to repair this mutation's function in the lab."

Cystic fibrosis occurs in about one in every 2,500 births in the Caucasian population, one in every 16,000 births in the African American population, and about one in every 90,000 births in the Asian American population.

"There are currently an estimated 23,000 patients diagnosed with CF in the United States, with an average survival age of 31 years," says Pamela Zeitlin, M.D., Ph.D., associate professor of pediatrics at Johns Hopkins and a co-author of the study. "4PBA has the potential to benefit more than two-thirds of these patients."

However, say Rubenstein and Zeitlin, it is not clear if this therapy alone would lead to significant improvement in patients. Even if the mutant protein reaches the surface of the cell, it still does not transport as much chloride as normal proteins do.

Rubenstein and Zeitlin are currently conducting clinical trials of 4PBA in CF patients who have the deltaF508 mutation.

Marie E. Egan, M.D., of Yale University, is also an author of the study.

The Johns Hopkins Children's Center is the children's hospital of the Johns Hopkins medical institutions. Maryland's most comprehensive acute-care hospital for children, the center, with its 177-bed hospital and more than 40 divisions and services, treats some 8,000 inpatients and more than 64,000 outpatients annually.


Nancy Volkers (410) 223-1747

Johns Hopkins Medical Institutions' news releases are available on a PRE-EMBARGOED basis on EurekAlert at http://www.eurekalert.org, Newswise at http://www.newswise.com and from the Office of Communications and Public Affairs' direct e-mail news release service. To enroll, call 410-955-4288 or send e-mail to bsimpkin@welchlink.welch.jhu.edu or 76520.560@compuserve.com.

On a POST-EMBARGOED basis find them at http://hopkins.med.jhu.edu, Quadnet at http://www.quad-net.com, ScienceDaily at http://www.sciencedaily.com or on CompuServe in the SciNews-MedNews library of the Journalism Forum under file extension ".JHM".

Joint Policy Board for Mathematics

Related Cystic Fibrosis Articles from Brightsurf:

Treating cystic fibrosis with mRNA therapy or CRISPR
The potential for treating cystic fibrosis (CF) using mRNA therapies or CRISPR gene editing is possible regardless of the causative mutation.

Cystic fibrosis: why so many respiratory complications?
Cystic fibrosis, one of the most common genetic diseases in Switzerland, causes severe respiratory and digestive disorders.

A newly discovered disease may lead to better treatment of cystic fibrosis
Cystic fibrosis is the most frequent severe inherited disorder worldwide.

New treatment kills off infection that can be deadly to cystic fibrosis patients
The findings, which are published in the journal Scientific Reports, show that scientists from Aston University, Mycobacterial Research Group, combined doses of three antibiotics -- amoxicillin and imipenem-relebactam and found it was 100% effective in killing off the infection which is usually extremely difficult to treat in patients with cystic fibrosis.

Cystic fibrosis carriers are at increased risk for cystic fibrosis-related conditions
A University of Iowa study challenges the conventional wisdom that having just one mutated copy of the cystic fibrosis (CF) gene has no effects on a person's health.

Rare mutations drive cystic fibrosis in Caribbean
Cystic Fibrosis (CF) in the Caribbean is dominated by unusual gene mutations not often observed in previously studied CF populations, according to comprehensive genome sequencing led by physician-scientists at UC San Francisco and Centro de Neumología Pediátrica in San Juan.

Cystic fibrosis carriers at increased risk of digestive symptoms
Researchers have found that carriers of the most common genetic variant that causes cystic fibrosis experience some symptoms similar to those of people with cystic fibrosis.

In cystic fibrosis, lungs feed deadly bacteria
A steady supply of its favorite food helps a deadly bacterium thrive in the lungs of people with cystic fibrosis, according to a new study by Columbia researchers.

Cibio knocks out cystic fibrosis
The fight against cystic fibrosis continues, targeting in particular some of the mutations that cause it.

Hypertonic saline may help babies with cystic fibrosis breathe better
Babies with cystic fibrosis may breathe better by inhaling hypertonic saline, according to a randomized controlled trial conducted in Germany and published in the American Thoracic Society's American Journal of Respiratory and Critical Care Medicine.

Read More: Cystic Fibrosis News and Cystic Fibrosis Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.