By Charles Craig

Sequana Therapeutics Inc., in collaboration with partner Boehringer Ingelheim GmbH, said it has cloned an asthma gene believed to be one of four or five mutated genes responsible for the debilitating chronic breathing disorder which affects 100 million people around the world.

La Jolla, Calif.-based Sequana released few details of the discovery pending publication in a scientific journal and submission of patent applications. The company planned to disclose the finding today.

Kevin Kinsella, Sequana's president and CEO, said his company's researchers used positional cloning to isolate the gene in humans in two and one-half years. He said the mutated gene is believed to be present in a significant number of asthma sufferers worldwide.

With positional cloning, researchers hunt for a mutated gene in people or animal models afflicted with the resulting disorder. Many are found first in mice, which are specifically bred for a disease, and then the corresponding genes in humans are located.

In people, positional cloning has been successful in identifying monogenic diseases, such as cystic fibrosis or hereditary breast cancer, where DNA samples from relatively small numbers of sufferers are required to locate the gene among the 80,000 to 100,000 genes in the human genome.

For polygenic diseases, one gene may be more culpable than another, and to find the culprit broadly responsible requires looking at different population groups. In asthma, Sequana officials have described a major gene as one involved in more than 10 percent of all patients.

Sequana began its search with blood samples from 300 closely related asthma sufferers on a remote island in the south Atlantic Ocean called Tristan da Cunha, and with help from the Samuel Lunenfeld Research Institute of Toronto-based Mount Sinai Hospital.

Thirty percent of Tristan da Cunha's residents are afflicted with asthma as compared to 5 percent of people in the U.S.

DNA from Caucasian and Asian groups of asthma sufferers in Toronto also was included in the study, as were genetic samples from people with asthma in San Diego and Australia. In all, DNA from 10,000 people was studied.

The asthma gene is one of two Sequana has targeted in two small regions on two chromosomes. (See BioWorld Today, Oct. 26, 1995, p. 4.)

In describing the gene discovery, Kinsella would say only that it is expressed in tissues of the bronchial pulmonary pathway.

Asthma is an inflammatory disease triggered by an environmental factor, such as an allergen. The inflammatory reaction causes a restriction of air passageways and the lungs.

Many biotechnology companies are hunting for asthma genes, but Sequana officials said none has reported cloning a major gene involved in the disease.

Kinsella said the find represents the first asthma gene cloned and the first polygenic disease gene positionally cloned in humans for a major common disorder.

Last year, Magainin Pharmaceuticals Inc., of Plymouth Meeting, Pa., said it discovered molecular targets from two genes believed to be regulators of allergic and inflammatory responses characteristic of asthma. (See BioWorld Today, March 13, 1996, p. 1.)

Magainin's genomics effort is led by Roy Levitt, who is director of the company's Institute for Molecular Medicine. Levitt's work at Magainin is built on his research at Johns Hopkins University, in Baltimore.

Sequana's discovery triggered a $2 million milestone payment from Boehringer Ingelheim, of Ingelheim, Germany. The company, which forged the alliance in 1995, has exclusive rights to use Sequana's asthma gene discoveries for creating drugs. Sequana retained rights for diagnostics.

Earlier this month Boehringer Ingelheim doubled its financial support for Sequana's asthma research efforts. Sequana officials said Tuesday their partner will pay another $5 million for subsequent asthma gene findings and $32 million in drug development milestones plus royalties.

Sequana's stock (NASDAQ:SQNA) closed Tuesday at $13.125, down $0.50.

In addition to research on asthma, Sequana is hunting for genes involved in diabetes, obesity, osteoporosis and schizophrenia. *