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Researchers Use Engineered Gene To Cure " Bubble Boy " Disease In Two Children

June 27, 2002

WASHINGTON (AP) -- Using an experimental technique that altered genes in

bone marrow stem cells, doctors cured two children who were born with the

bubble boy " disease that leaves patients defenseless against infection.

The children were born with a form of severe combined immunodeficiency

disorder caused by a gene flaw that blocks production of an enzyme called

ADA, which is essential to make disease-fighting immune cells.

Doctors in Italy and Israel cured the children with injections of bone

marrow stem cells that had been altered to contain the missing enzyme gene.

In a matter of months, the researchers report in this week's edition of the

journal Science, both children had healthy immune systems.

Dr. W. French , a University of Southern California researcher and a

pioneer in the field, said the research is an important advance for the

entire concept of gene therapy.

" This gives a boost to the whole field because it proves our basic premise

that if you can get enough gene-engineered cells into the patient it will

cure the disease, " said in a telephone interview Wednesday. " That

is very important and therefore this is a very exciting paper. "

was the first to try genetic engineering to cure the ADA, or

adenosine deaminase, form of severe combined immunodeficiency disorder, or

SCID. His technique changed the gene in blood cells instead of the bone

marrow. Two of 's early patients have led normal lives since the

1990 procedure, but they require periodic shots of ADA enzyme to assure

healthy immune systems.

The technique used by the Italian and Israeli researchers, , appears

to be a cure that will require no further shots.

" That means that these patients have normal functioning immune system, " he

said. Technically, added, the cure cannot be considered complete

for many decades while doctors monitor the patients, but for all intents and

purposes it is a cure.

SCID is rare, striking only about 50 children a year. In the past, the

disorder was always fatal, with the children usually dying in infancy of

uncontrollable infections.

Starting in the 1960s, doctors treated SCID patients by isolating them in

sterile environments. One of the most famous such patients was a Houston boy

who spent all 12 years of his life in a plastic bubble filled with filtered

air. He became known as " the bubble boy. " He died in 1984 when, at his

insistence, doctors tried a bone marrow transplant.

Since then, a number of researchers have tried to cure some forms of SCID

with gene therapy. At least a handful of patients appear to have developed

healthy immune systems after gene therapy for one type of SCID, called gamma

C.

But the new study is the first to report a cure for ADA-SCIDS, the most

complex form of the immune system disorder, said.

In the new study, the Italian and Israeli researchers treated two children,

a seven-month-old and 2{-year-old, who were born without functioning normal

ADA enzyme genes.

The researchers corrected the inherited flaw by changing the genes in the

stem cells of the bone marrow that make blood cells.

To do this, the doctors removed stem cells from the bone marrow of each

patient and then used a virus to insert into these cells the normal gene for

ADA. The stem cells where then re-injected and naturally migrated to the

bone marrow.

The researchers report in the journal Science that shortly after the

procedure, the bone marrow in both children began producing normal

disease-fighting blood cells. Within months, their immune systems were able

to overcome some common childhood infections that previously had not

responded to treatment. They were even able to be successfully immunized

against tetanus.

The key to their success, said , may have been a novel use of a

chemotherapy drug by the researchers. They injected both patients with the

drug which partially killed the youngsters bone marrow. When the new stem

cells were injected, the bone marrow was primed to use those cells to make

new blood cells.

This allowed the injected stem cells to rapidly proliferate and become the

dominant blood-making cells in the patients' body, said.

Claudio Bordignon of the San Raffaele Telethon Institute for Gene Therapy in

Milan, Italy, was the senior author of the study. The senior Israeli

researcher was Prof. Shimon Slavin of the Hadassah University Medical Center

in Jerusalem.

Copyright 2002 The Associated Press. All rights reserved