MEDICINE

A test case in hope

A new treatment could cure cystic fibrosis

MARK NICHOLS May 3 1993
MEDICINE

A test case in hope

A new treatment could cure cystic fibrosis

MARK NICHOLS May 3 1993

A test case in hope

MEDICINE

A new treatment could cure cystic fibrosis

Ever since scientists began to crack the riddle of human genetics two decades ago, medical experts have predicted that genetic engineering would eventually produce cures for deadly human ailments. But so far, the growing ability of scientists to manipulate genes has led to improved treatments for only a handful of diseases. A medical experiment launched in Bethesda, Md., last week could soon change that by providing a potent new treatment for

cystic fibrosis (CF), the inherited disorder that afflicts more than 30,000 North Americans, including about 3,000 Canadians. Armed with crucial information that a Canadian scientist helped to discover, Dr. Ronald Crystal of the Cornell University Medical College used a genetically altered virus to carry millions of laboratory-bred genes into the nose and one lung of a CF patient. Crystal’s ultimate objective: to offset the influence of a faulty gene that causes CF victims’ lungs to become dangerously congested, and kills many of them by the age of 30.

Crystal administered the infusion of new genes at the National Heart, Lung and Blood Institute in Bethesda.

The patient was a 23-yearold man whose name was not released. Crystal said

that during the next six months, nine more cystic fibrosis patients would receive the treatment in a program designed to see if the therapy works and to determine whether there are any dangerous side effects. Crystal said that if the current program is successful, two more test programs will be held with larger numbers of patients. If the treatment works, he added, “it has the potential for curing lung abnormalities in the patients and extending their life expectancy.”

Crystal’s program was welcomed by experts. Declared Dr. Michael Hayden, director of the Adult Genetics Clinic at the University of British Columbia’s University Hospital in Vancouver: “This is very exciting, and very promising.” Cathleen Morrison, executive director of the Canadian Cystic Fibrosis Foundation, was more cautious. “This is ex-

citing,” she said, “but it is only the first step towards a new treatment.”

The prospects of finding new ways of treating CF improved dramatically in 1989 when a research team led by Lap-Chee Tsui, a scientist at Toronto’s Hospital for Sick Children, and a group of medical researchers at the University of Michigan in Ann Arbor, located the defective gene that causes cystic fibrosis Because the gene does not function properly, chloride is unable to pass through the

walls of cells in a CF victim’s lungs. That causes mucus to build up in the patient’s lungs. As a result, CF victims usually need to use an aerosol mist several times a day to loosen the congestion.

Crystal, a 52-year-old internist who is head of pulmonary and critical care medicine at Cornell University Medical College in New York City, said that he devised his plan for treating cystic fibrosis four years ago. He was aware that the adeno virus, one of the causes of the common cold, zeros in on cells in the same part of the lungs that are affected by CF. Explained Crystal: “I thought that since the virus knows how to get into the cells, why not use it as a delivery van” to carry healthy genes into the lungs. After Tsui and the U.S. researchers identified the CF gene, it became possible to test his idea. Lab-

oratory scientists helped to genetically alter the virus to remove its dangerous properties and insert a copy of a healthy CF gene. In his first test, Crystal used nose drops and a thin, flexible tube to inject about 20 million copies of the altered virus into his first patient. Crystal said that he hopes the healthy genes now will make cells in the patient’s body function normally.

If it works, Crystal’s treatment would be a major breakthrough. During the past decade, scientists have identified the genes responsible for more than a score of illnesses. Those findings have made it possible for medical personnel to screen fetuses and individuals who may be susceptible to illnesses ranging from Huntington’s disease, a degenerative neurological disorder, to certain forms of cancer and mental retardation. But so far, effective treatments have been developed for only a few genetically caused illnesses. They include familial hypercholesterolemia, which causes dangerous buildups of cholesterol in victims. It can now be treat-

ed with a family of drugs. Crystal’s treatment, if successfiil, would be the first form of gene therapy to treat a major disease. Hayden says that Crystal’s experimental program could herald the beginning of a new era in genetic medicine. “In this case, the discovery of the CF gene has led very quickly to the discovery of a possible therapeutic method in which the gene itself becomes the treatment.” Hayden added that after years of research “we may be just on the verge of an explosion” of developments in genetic medicine. If that proves to be the case, the victims of many cruel diseases will have new reasons to appreciate science’s growing understanding of the human body’s complex and sometimes faulty chemistry.

MARK NICHOLS