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Compound may point way to improve asthma treatment

Monday, January 12, 2004

WASHINGTON -- Researchers have found a compound that blocks the production of excessive mucus, which could point the way to better treatments for asthma, chronic bronchitis, cystic fibrosis and other diseases.

Mucus, a thick fluid produced by mucus membranes, moistens and protects areas such as the digestive and nasal canals. Excess production of mucus in diseases such as asthma can block airways.

Scientists working with asthmatic mice found that excess mucus production could be sharply reduced or eliminated using a peptide called MANS. It blocks the protein that causes the excess secretion.

The findings of the research team, led by Kenneth B. Adler of North Carolina State University, are reported in the February issue of the journal Nature Medicine. Their paper was published Sunday in the journal's online issue.

"These findings could be very important as far as providing direction to eventually lead to therapeutic treatment" of certain respiratory diseases, Adler said in an e-mail interview.

He said it could take time before such a treatment would be ready for testing in people.

Dr. Philip S. Norman, an asthma expert at Johns Hopkins University in Baltimore, noted that excess mucus is a major problem in asthma and that finding a safe way to limit it would be a help toward treatment.

It would not be a cure, however, because other symptoms of asthma occur, said Norman, who was not part of the research team.

No side effects

No side effects were noted in the mice, Adler said, but they were treated for less than an hour. Longer-term studies would be needed to assess the safety of the compound, he said.

Nevertheless, depending on the dose, the chemical was effective in reducing excess mucus production in different types of mice.

In one group, excess mucus was reduced by 80 percent or more, with larger doses cutting the mucus to below normal flows.

In a different strain of mice, excess mucus was cut by between 50 percent and 100 percent, depending on dosage. A third group, using a different chemical to induce the allergy, saw a reduction in excess mucus by between 20 percent and 90 percent as doses were increased.

The researchers found that mucus production requires a protein called myristoylated, alanine-rich C-kinase substrate, or MARCKS.

In lab tests, they found that an amino acid fragment called myristoylated N-terminal sequence, or MANS, reduces mucus flow, possibly by inhibiting the attachment of MARCKS to membrane cells.

They then turned to the mouse experiments to see if the same would result would occur.

In addition to the researchers at North Carolina State, the team includes scientists at the Pasteur Institute, Paris; the University of Sao Paulo, Brazil; and the School of Veterinary Medicine, Hannover, Germany.

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