Novel Gene Therapy Effectively Reduces Asthma Symptoms in Mice

http://www.100md.com 2003年11月6日 中华基因网

     A novel nasal spray containing minuscule particles that deliver therapeutic protein-producing genes effectively reduces allergen-induced airway inflammation and hyper-reactivity, the hallmark symptoms of asthma.

    The study, by University of South Florida scientists, was posted online Monday, October 27, 2003, in the Journal of Genetics Vaccines and Therapy.

    "By treating asthmatic mice with this gene therapy, we have allowed their lungs to produce the protein, interferon gamma, that is needed to reduce asthmatic symptoms," said Shyam S. Mohapatra, PhD, principal investigator, professor of medicine, and director of basic research for the division of allergy and immunology and the Joy McCann Culverhouse Airway Disease Center.

    "Within six hours of intranasal delivery the mice showed reduced airway inflammation."

    Based on these findings in mice, the National Institutes of Health (news - web sites) has awarded $1.16 million to Mohapatra and his team to determine if the treatment will work in and be safe for humans with asthma.

    Asthmatics produce relatively low amounts of interferon gamma, and efforts to treat with the protein directly have not proven successful, because 50 percent of the protein degrades within one hour of administering it.

    "We want the cells in the lung to make interferon," Dr. Mohapatra said.

    "This method has potential to help alter immune response, so that the treatment may only need to be administered once a week rather than several times daily like current asthma treatments.

    "And now that scientists and clinicians consider allergy, sinus and asthma conditions as one disease, this therapy has the potential in the future to modify allergic immunotherapy by reducing injections and increasing effectiveness."

    Mohapatra and his team selected chitosan nanoparticles as a delivery method for interferon gamma gene. Previous efforts to deliver interferon gamma gene to the cells in the lungs have used viruses as a vehicle, but eventual immune resistance and side effects of the virus left scientists looking for a new delivery method, said Dr. Mohapatra.

    Chitosan is a carbohydrate that comes from shellfish, is naturally biodegradable and is used in many "fat buster" products. It sticks to epithelial cells, respiratory system cells that produce mucous, delivering the interferon gamma gene right where it is needed.

    "The problem with many drugs, including drugs to treat asthma, is that they accumulate in the body," Dr. Mohapatra said. "Chitosan is advantageous as a drug delivery method because it is naturally broken down by the body."

    Nanoparticles are the smallest particles known to man. At USF, faculty use nanotechnology in marine science, medicine, natural science, mathematics and engineering. Medically, nanoparticles have been used in treating terminal lung cancer patients.

    "We are possibly the only lab in the United States using nanoparticles to treat asthma," Dr. Mohapatra said. "When the NIH awarded our grant, experts there said we may be at least 10 years ahead of all others with this method."

    Source: University of South Florida

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