WASHINGTON, D.C. -- Good news for Bill Clinton. Ourperpetually stuffed-up president may no longer have to avoidhis daughter's cat if ImmuLogic Pharmaceutical Corp.'s latestproject is successful.
News of the chief executive's potential succor came lastThursday from the National Institute of Allergy and InfectiousDiseases (NIAID), as about 60 scientists gathered to discuss thefuture of asthma and allergic disease research. Phase II trialsfor a new kind of anti-allergen, ImmuLogic's CatVax fortreating cat allergies, should begin toward the end of thismonth.
The scientists also heard about ongoing research at JohnsHopkins University in Baltimore that may point the way toother allergy therapies, as well as about family linkage studiesto find the genes that cause asthma.
The president undoubtedly suffers much amidst Socks' dander,but he suffers not alone. Roughly 10 percent of Americans,including many asthmatics, are allergic to cats, said BarbaraWallner, vice president for clinical research at ImmuLogic(NASDAQ:IMUL) of Cambridge, Mass.
The dominant cat allergen is Fel dI, named for Felis domesticus.Scientists believe that all allergies are mediated throughimmunoglobulin E (IgE), and several studies have found thatFeI dI-specific IgE is present in at least 80 percent of patientswith cat allergies.
The problem with allergy shots, the current treatment, stemsfrom the fact that they are made from extracts of the materialthat is associated with the allergy -- cat pelts in the case of FeldI, Dick Bagley, ImmuLogic's chief executive officer, toldBioWorld.
Exposure to small amounts of allergen lets the body becometemporarily habituated without reacting. But there is a delicatebalance between habituation and reaction. Every year, saidBagley, allergy shots kill a few people by causing anaphylacticshock.
ImmuLogic's solution to the problem was to find the fraction ofthe allergen molecule that is recognized by antibodies. Intheory, at least, the chances are great that this fraction will bedifferent from that which sets off the allergic reaction bybinding to IgE.
ImmuLogic is collaborating with Marion Merrill Dow to searchfor "what we feel are the five major worldwide allergens,"Bagley explained. Besides cats, these include Japanese cedarpollen (which is indigenous to Japan), ragweed (which isindigenous to the U.S., but spreading), house dust mite (whichis ubiquitous) and lawn grasses.
At Johns Hopkins, another line of research is suggesting furtheravenues for asthma therapy. Eosinophils, scavenging whiteblood cells that kill invading bacteria with the toxic chemicalsthey pack, may cause many of the symptoms of asthma. They"are found in unexpectedly high proportions in the airways andlung tissue in asthmatic subjects," explained Robert Schleimer,of Johns Hopkins' Asthma and Allergy Center.
Eosinophils stick to endothelial cells, and the operatingassumption is that their chemical weapons are contributing tothe airway inflammation seen in asthmatics. Therapy, then,might involve preventing adhesion.
Laboratory studies have uncovered some of the factors thatmediate sticking. The molecules that actually cling together arethe surface proteins VLA-4 and VCAM-1, which are present oneosinophils and activated endothelial cells, respectively. Butantibodies to VCAM-1 have been found to inhibit adhesion.
Similar types of evidence suggest that members of the selectinsupergene family may also mediate adhesion. But the relativeimportance of these mechanisms remains to be established,said Schleimer.
Other researchers at Johns Hopkins Medical School andelsewhere have just begun searching for the genes involved incomplex genetic disorders, including asthma, said DeborahMeyers, professor of medicine and epidemiology at the Centerfor Medical Genetics. "The major aim of this study is to identifymajor genes for asthma by linkage with highly polymorphicDNA markers with a systematic search of the genome," saidMeyers. "When a linkage is detected, candidate genes in thatarea will be studied." The researchers have assembled 300markers to aid in this search.
Studies are under way in Holland and at four centers in the U.S.
The Dutch study has the advantage of medical records forasthmatics that go back 30 years, that will resolve questionssuch as whether what adults remember from childhood wasreally childhood asthma or a disease with similar symptoms,such as bronchitis.
The U.S. studies, under the auspices of the Nationals Institutesof Health, include a variety of racial and ethnic populations:blacks, Caucasians, Hispanics, Hutterites and Amish. TheHutterite population has sustained considerable inbreeding.
-- David C. Holzman Special to BioWorld
(c) 1997 American Health Consultants. All rights reserved.