NEW YORK (Reuters Health) - Individuals with cystic fibrosis (CF) have higher ratios of arachidonic to docosahexaenoic acid in CF-affected tissues than do individuals with other inflammatory disorders, investigators report in The New England Journal of Medicine for February 5th.
“We think that this fatty acid imbalance may be causing too much inflammation,” lead author Dr. Steven D. Freedman told Reuters Health, “so correcting the imbalance may decrease inflammation” in patients affected by cystic fibrosis transmembrane regulator (CFTR) gene mutations.
Dr. Freedman’s team previously showed that levels of these two fatty acids are altered in mice lacking the CFTR gene (see Reuters Health report, October 11, 1999). Although deficiencies in fatty acids have been recognized in patients with CF, it was not known if the alterations in CFTR-regulated tissues from patients with CF matched those of the knockout mice.
The researchers therefore analyzed fatty acid levels in tissue specimens from 38 individuals with CF, 13 individuals heterozygous for CFTR mutations, 11 with inflammatory bowel disease, 9 with upper respiratory tract infection and 16 with asthma.
The median ratio of arachidonic to docosahexaenoic acid in nasal biopsies was 13.0 in CF patients with pancreatic insufficiency, 10.7 in CF patients with normal pancreas function, and 5.8 in healthy control subjects. Similar patterns were seen in rectal biopsy tissue.
The ratios of arachidonic to docosahexaenoic acid in obligate heterozygotes and those with asthma and upper respiratory tract infections were intermediate between those of CF patients and healthy controls. Ratios in patients with inflammatory bowel disease were lower than in control subjects.
The findings suggest that the differences in fatty acid levels could not be attributed to abnormal intestinal absorption of fat due to pancreatic insufficiency, the authors note.
According to Dr. Freedman, his group is collaborating with Genzyme Corporation to develop a docosahexaenoic acid-based compound for the treatment of disorders caused by CFTR mutations, including chronic sinusitis, male infertility and primary sclerosing cholangitis, as well as CF.
Because mouse studies showed that their agent corrected CFTR-related fatty acid abnormality and reversed histological changes in multiple tissue types, without causing toxicity, the investigators hope to begin human clinical trials soon.
However, Dr. Freedman agrees with the views of Dr. Birgitta Strandvik, at Goteborg University in Sweden, who in an editorial suggests that treatments to correct fatty acid abnormalities “should be approached with great caution.”
“It’s always important to be cautious,” he added. “It’s probably unlikely without gene therapy that any one drug will be the cure.” In fact, he compares treatment of CFTR-related abnormalities to that for cancer, for which “multiple drugs are required.”
Source: N Engl J Med 2004;350:560-569,605-607. [ Google search on this article ]
MeSH Headings:Dietary Fats: Dietary Fats, Unsaturated: Docosahexaenoic Acids: Fats: Fish Oils: Ion Channels: Membrane Glycoproteins: Membrane Proteins: Mice, Mutant Strains: Drugs, Investigational: Fatty Acids, Omega-3: Chloride Channels: Mice, Knockout: Cystic Fibrosis Transmembrane Conductance RegulatorCopyright © 2002 Reuters Limited. All rights reserved. Republication or redistribution of Reuters content, including by framing or similar means, is expressly prohibited without the prior written consent of Reuters. Reuters shall not be liable for any errors or delays in the content, or for any actions taken in reliance thereon. Reuters and the Reuters sphere logo are registered trademarks and trademarks of the Reuters group of companies around the world.
