SAN DIEGO - A gene therapy experiment which began with the birth of a baby two years ago is showing signs of success, reported researchers at a meeting of the Society for Pediatric Research .

The novel gene therapy for severe combined immunodeficiency disease (SCID) may offer hope for a variety of immune-deficiency disorders including AIDS, according to Donald Kohn, M.D., Director of Gene Therapy Program, Children's Hospital, Los Angeles, CA.

Dr. Kohn and colleagues performed a gene transfer procedure in a four day old patient, Andrew Gobea, who was born with ADA-SCID. This form of SCID is characterized by the absence of gene to produce adenosine deaminase (ADA), an enzyme critical to formation of white blood cells. The onset of SCID is usually within first three months of life. If left untreated, SCID has a fatal progressive course by age two.

Following in utero diagnosis, the first step in the gene therapy procedure involved harvesting hematopoietic stem cells from umbilical cord blood. The cell population was purified and amplified using stem cell growth factors. A cloned normal ADA gene was then added via a viral vector, a deactivated Maloney murine leukemia retrovirus. This inactivated virus acts as a kind of 'Trojan horse', he explained.

This is essentially the same protocol that has been used for gene therapy of SCID in five older children in Europe and several children in the U.S. However, there is a significant difference in the new protocol. In previous studies, the ADA gene has been inserted in the same virus vector, but via stem cells obtained from bone marrow, or in some cases, via T-cells obtained from patients' sera.

"This is the first time cord blood has been sued as a source of stem cells. This is an important step forward. The advantages of using cord blood is that is offers a good source of stem cells, and it can be utilized immediately after birth. In addition, the stem cells can be obtained non-invasively, which is easier on the baby," noted Dr. Kohn, who is also an Assistant Professor, department of pediatrics, University of Southern California School of medicine, los Angeles, CA.

This is also the first time gene therapy has been conducted on newborns. The latest laboratory results indicate that the transferred genes have been picked up by three percent of the patients' T-cells. The next step will be to slowly taper off injections of ADA the patients have been receiving to determine if their immune systems can function on their own.

"If we can correct genetic defects at birth in immune-deficiency disorders, we can prevent the severe problems that follow. This may give us a new way to treat genetic diseases of the blood, such as sickle cell anemia or hemophilia," he said.

Dr. Kohn's group is also involved in attempts to treat patients with Gaucher's disease using gene therapy. Gaucher's disease is a familial autosomal recessive disorder of lipid metabolism. Clinical manifesations include hepatosplenomagaly, skin pigmentation and skeletal lesions. An associate of Dr. Kohn, Cory Raffel, M.D., is conducting a gene therapy protocol for the treatment of patients with malignant pediatric brain tumors.

Dr. Kohn is also involved with research into the genetic basis of HIV disease. An NIH protocol is now underway to determine whether gene therapy techniques could prevent immune impairment in HIV disease. The protocol involves obtaining bone marrow from HIV patients, isolating stem cells, and then inserting altered genes using a similar approach to the SCID experiment. Dr. Kohns lab has identified several genes which, in vitro experiments, make T-cells resistant to HIV infection.

"We have found genes that we can put into cells that will protect the cells from being infected with the AIDS virus. We hope these techniques can be used to engineer patients cells to resist infection. with HIV. This may enhance patients' immune responses sufficient to survive HIV infection," he said.

Transmitted: 95-05-12 20:00:51 EDT

Science Updates Index

What's News Index

Feedback