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Scientists Use Gene Therapy to Cure Immune Deficient Child

  [ 11 votes ]   [ Discuss This Article ]
www.ProHealth.com • July 10, 2002


By Judy Siegel-Itzkovich, Jerusalem

An international team of scientists has managed to cure a child with severe combined immunodeficiency (SCID) using gene therapy.

Patients with SCID are usually treated by replacing an essential enzyme, adenosine deaminase, which is lacking in such people. But this treatment is effective for only a couple of days at a time and is expensive. Some patients can have a bone marrow transplant, but only if a good match can be found.

The team was headed by Professor Shimon Slavin, of the Hadassah University Hospital in Jerusalem, and his colleagues Dr Shoshana Morecki and Dr Memet Aker. They collaborated with Dr Allesandro Aiuti and other staff from the San Raffaele Institute for Gene Therapy in Milan, Italy. They published their results in the journal Science last week (2002;296:2410-3).

The patient, whose first name is Salsabil, is a baby Arab girl from east Jerusalem who had to live for the first seven months of her life inside a plastic bubble to protect her from all pathogens because she totally lacked an immune system.

Although the condition is diagnosed in only a few dozen infants around the world each year (in most cases the babies die before a diagnosis is made and they can be treated), Professor Slavin said the treatment can be used to cure other genetic diseases in which patients are born lacking a vital enzyme.

"Among these are Gaucher's syndrome, metachromatic leukodystrophy, and Hurler's syndrome," he said.

A decade ago scientists began treating SCID by using gene therapy to alter T cells and stem cells. Although a theoretical success, these experiments failed to have a real impact on the babies' condition because only a tiny amount of the genetically abnormal bone marrow products was repaired, Professor Slavin explained.

The patients still required adenosine deaminase replacement treatment to survive because the "good" cells were overwhelmed by the much larger number of genetically abnormal cells remaining in the host.

Professor Slavin believed that if he could give the genetically treated cells a "biological advantage," they could overcome the more numerous abnormal cells. He asked Dr Claudio Bordigan, head of the San Raffaele Institute, to supply adenosine deaminase retroviral vector.

At Hadassah University Hospital 15 months ago, Professor Slavin's team gave Salsabil a mild form of chemotherapy, called non-myeloblative conditioning, to suppress her defective bone marrow cells, and prepare the ground for the transfused cells to multiply. The team then introduced, using a genetically engineered virus, a healthy copy of the missing gene for adenosine deaminase into her purified bone marrow stem cells.

No enzyme replacement had been given at any stage, showing that the gene alteration treatment was responsible for the cure.

The baby recovered quickly, and within a few weeks the number of lymphocytes in her blood rose dramatically. Within a month she was out of isolation and went home perfectly well.

She is the third baby with SCID born to her parents. The first child died from the condition and the second, Salsabil's older sister Tasmin, survived after receiving a transplantation of allogeneic umbilical cord blood from a younger brother.

After the first child died, Hadassah doctors froze umbilical cord blood cells from each successive baby for possible treatment of subsequent siblings.

Salsabil's immune system is thought to be working properly, because after she was exposed to chickenpox in the family she developed antibodies against the disease.

(c) 2002 BMJ.



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