Researchers at Childrens Hospital in Los Angeles have reportedevidence that a gene therapy for treating three infants with severecombined immunodeficiency (SCID) appears to be working.

Donald Kohn, director of the hospital's gene therapy program,released results of a two-year follow-up study Wednesday at apediatric conference in San Diego. He also said the data weresubmitted two weeks ago for publication in a scientific journal.

The study, begun in May 1993, involved using retroviral vectors todeliver ex vivo a normal copy of an adenosine deaminase (ADA)gene to stem cells from the umbilical cord blood of newbornsdiagnosed with SCID. Youngsters with the potentially fatal diseaseare missing the enzyme, ADA, and cannot produce infection-fightingwhite blood cells.

CD34+ cells from the umbilical cord blood of the infants weretreated once a day for three days with the retroviral vectorscontaining the normal ADA gene. The cells were then reintroducedwith the goal of enabling the youngsters to make their own cellscontaining ADA.

All three babies also receive ADA replacement therapy in the form ofbovine PEG-ADA, which keeps them healthy.

Kohn told BioWorld Today that after one year, an examination of theinfants' bone marrow showed at least 2 to 5 percent of stem cells witha normal ADA gene.

After 18 months, the researchers were able to reduce the dosage ofPEG-ADA for the infants and determined that up to 3 percent to 5percent of the youngsters' own T cells (white blood cells) had thetransferred ADA genes.

In presentation of his findings Wednesday, Kohn said the resultsshow "that retroviral-mediated gene transfer can insert genes intolong-lived hematopoietic stem cells from umbilical cord blood, whichare capable of engrafting and functioning in vivo for at least 18months."

Kohn told BioWorld Today it is too early to tell if the gene therapycan cure the children.

"If we can slowly cut back on the [PEG-ADA] enzyme dosages thatwould be the endpoint," he said.

The retroviral vectors used in the study were produced by GeneticTherapy Inc., of Gaithersburg, Md. They are the same vectors used inthe first gene therapy trial in 1990, which treated SCID in two girlsby inserting the ADA gene in lymphocytes.

Marc Schneebaum, Genetic Therapy's chief financial officer, said theSCID study may indicate that "the concept of treating stem cells isone that has implications in gene therapy for other diseases."

In theory, the advantage of altering stem cells is that the body thenwill produce more mature cells that will correct the disease.

Kohn, using Genetic Therapy's retroviral vectors, soon will begin astudy examining gene therapy for treating stem cells from bonemarrow of adults with Gaucher disease.

Although the gene therapy appears to be working with stems cellsfrom the umbilical cords of newborns, the researchers said thatdoesn't indicate the procedure will be as effective in progenitor cellsof adults. n

-- Charles Craig

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