Gene therapy may give newborn second chance 4-day-old makes medical history

THE BALTIMORE SUN

LOS ANGELES -- Andrew Gobea doesn't know it, but over the weekend he made medical history. The procedure, which took place behind a plastic curtain in a sterile room at Children's Hospital Los Angeles, lasted just two minutes. Andrew, 4 days old, slept through it all, his tiny fingers curled under his right ear.

The 6-pound-12-ounce baby with thick black hair was born Tuesday evening with an immune system that doesn't work. On Saturday, a doctor infused the infant with a teaspoon's worth of genes that are intended to cure the defect that, if left untreated, kills most of its victims by the time they reach their first birthday.

The treatment makes Andrew the first newborn ever to undergo a cutting-edge brand of medicine known as gene therapy. It also employs, for the first time, a novel twist on previous attempts at genetic engineering: the use of blood drawn from the umbilical cord that was snipped from the baby at birth.

For Andrew, the highly experimental operation means a chance to live a normal life, without drugs that cost as much as $250,000 a year. For his parents -- who three years ago lost an infant daughter to Severe Combined Immune Deficiency, the same disease that plagues their newborn boy -- it means the chance to have a surviving child.

For a team of four pediatric immunologists and hematologists at Children's, Saturday's effort was the culmination of six years of painstaking investigation, of late nights in the laboratory, frustrating wrong turns and, finally, the rare heady rush that comes when science moves out from under the microscope and into the operating room.

And for thousands of other infants who will be born with genetic disorders that can be diagnosed in the womb -- hemophilia, sickle cell anemia and Gaucher's disease, among others -- it represents a step toward treatment immediately after birth, and hence freedom from the debilitating effects of those diseases.

It was as emotional as it was revolutionary; when Leonard Gobea asked if he could help inject the gene-altered cells into his son, Dr. Donald Kohn took the unusual step of allowing him to press on the syringe, which was attached to an intravenous line. "It's not rocket science," the doctor explained afterward. "It's just pushing a little plunger. He wanted to be a part of doing it, and I thought that was great."

It will likely be another six months before doctors know if Andrew's treatment has worked. During that time, he will also be given twice-weekly injections of a drug containing an enzyme to shore up his immune system. Until doctors are certain the drug is working, he will remain in isolation at Children's.

"We wear two hats," said Dr. Kohn, the gene therapy expert who headed the experiment. "We want to do the right thing for our patients, and we want for this family to have a healthy baby. But we're also researchers, and we want to further our research goals."

It was those two forces -- the hope of Crystal Emery and Leonard Gobea to have a healthy baby, and the desire of Dr. Kohn and his colleagues to push the limits of the gene therapy -- that set the new parents and the doctors on a converging course that began months before Andrew's birth.

They are a young couple, Ms. Emery and Mr. Gobea. She is 19 and he is 20. They are not married. She lives with her parents in California's Imperial Valley town of El Centro near the Mexican border; he with his parents a few miles away in Holtville.

He is a part-time steam driller and sand blaster who dropped out of high school. She wears a small diamond on her left ring finger, but marriage and a home of their own must wait, Mr. Gobea says, until he gets better situated with a job.

The "Bubble Boy" disease

They have been dating since they were in junior high, and after all these years they say they might as well be husband and wife. They had their first child when they were 16 and 17.

Chastity Gobea lived five months. The first sign she was sick came at age two weeks, when her navel would not heal. Then there were two bouts with pneumonia. By the time doctors discovered her genetic disorder, it was too late.

Her death brought news to her parents: Each carries a defective gene that causes ADA deficiency, a form of Severe Combined Immune Deficiency (SCID). The letters ADA stand for adenosine deaminase, an enzyme that enables the immune system to fight infection.

SCID is extremely rare. Each year just 100 Americans are born with the disease. The most famous victim was David, the "boy in a bubble," who lived in isolation in a Houston hospital for 12 years before his death in 1984. ADA deficiency is the most common form of SCID, accounting for 25 percent of all SCID cases.

But gene therapy, which offers the best hope, is still in its infancy. Just 47 gene therapy projects, most of them designed ** to treat cancer patients, are now either approved or under way worldwide, according to Dr. W. French Anderson, a USC geneticist who is a pioneer in the field.

Although the technology for gene therapy is sophisticated, the techniques remain crude. Most gene therapy experiments employ a class of viruses known as "retroviruses" to carry missing genes into target cells. But scientists have yet to perfect methods for transferring the genes into cells, and once inside, the genes do not always work.

ADA deficiency lends itself well to gene therapy, primarily because the disease can be corrected with just a small percentage of functioning genes.

The world's first approved gene therapy experiment -- conducted in 1990 by Dr. Anderson and Dr. Michael Blaese at the National Institutes of Health -- was performed on two ADA deficient girls, ages 9 and 4, who had been treated with experimental drugs prior to the therapy.

The experiment on Andrew Gobea is being conducted in conjunction with NIH. Dr. Blaese, who was present Saturday, agreed to serve as a collaborator so that the government would give the experiment emergency approval in time for Andrew's birth.

In conjunction with San Francisco doctors, the team will repeat the procedure early this week on a baby boy born Friday in that city.

"The Holy Grail"

Andrew's drama began Tuesday, at 6:25 p.m., at Los Angeles' Hospital of the Good Samaritan, where Ms. Emery gave birth. Immediately, the obstetrician snipped the newborn's umbilical cord and began to draw blood. It was crucial that as much as possible be obtained. Dr. Kohn and his colleagues were hoping for 100 cubic centimeters -- about 2/5 of a cup. They got half that.

With the blood drawn, a long night of laboratory work lay ahead, as technicians began the intricate process of isolating Andrew's "stem cells" -- the parent cells of all other blood cells. For weeks, they had been practicing on a prototype machine borrowed from a Seattle-based firm, 17 practice runs in all.

Most gene therapy experiments target white blood cells; the therapy must be repeated every several months when the white cells carrying the new gene die. But stem cells stay alive in the marrow, spawning new cells. Thus if Andrew's therapy works, he will be cured.

"The stem cell is the holy grail of this work," says Kohn, who has spent the past six years in his lab at Children's Hospital working on these techniques. "It's the cell that we want to fix. If we can genetically fix the stem cell, then all the cells that it makes will have the right gene."

But experts say the process is fraught with obstacles. Stem cells are very rare in the blood, composing less than one-tenth of 1 percent of all blood cells, and are difficult to isolate. And for reasons that scientists do not entirely understand, genes introduced into stem cells do not function as well as those introduced into white blood cells.

It took Children's Hospital technicians nearly six hours of careful, intense work to separate the stem cells from the rest of Andrew's blood. They began with 500 million blood cells and ended with 3 million -- about one teaspoon's worth. But the number of true stem cells remains a mystery, part of the guessing game making Saturday's experiment just that -- an experiment.

Once all the additions were made, the mixture was put in an incubator, where it spent the rest of the week, waiting for Andrew.

Copyright © 2019, The Baltimore Sun, a Baltimore Sun Media Group publication | Place an Ad
37°