Public Release: 

New gene therapy protocol: First successful treatment for 'bubble babies'

Hadassah, the Women's Zionist Organization of America



Prof. Shimon Slavin with Baby Salsabil. Click here for a high-resolution image.

Jerusalem (June 21, 2002) -- A lifesaving protocol that has wide ranging consequences for the successful treatment of genetic diseases has been developed by a team of Israeli and Italian researchers for the treatment of children born without immune systems. A description of the first successful application of the new treatment appears in the June 28 issue of the journal Science.

The procedure, which improves an existing protocol to give a biological advantage to genetically altered stem cells, resulted in a complete reversal of severe combined immunodeficiency (SCID), a condition caused by the lack of an essential enzyme, adenosine draminase (ADA). Children born with an acute form of SCID are known as "bubble babies" and have to be kept in isolation units to prevent them from coming in contact with infectious elements.

The research was led by Prof. Shimon Slavin, Dr. Shoshana Morecki and Dr. Memet Aker of Hadassah-Hebrew University Medical Center in Jerusalem, in collaboration with Dr. Allesandro Aiuti and his colleagues from the San Raffaele Institute for Gene Therapy in Milan, Italy.

According to Slavin, Head of Department of Bone Marrow Transplantation at Hadassah Medical Center, the significance of this new development extends beyond those immediately affected by SCID and has the potential to be equally effective in curing similar genetic diseases, such as Gaucher's and other diseases caused by enzyme deficiency.

"The concept can be applied to all genetic diseases where there is a need to engineer stem cells to produce normal products, especially when patients have no matched donor available for safe bone marrow transplantation," Slavin said.

Conventionally, such patients are usually treated with ADA replacement therapy in an attempt to rescue the immune system. This replacement therapy, however, is not a long-term solution; it is only effective for one or two days at a time and is extremely expensive. Bone marrow transplantation, preferably from a matching donor, is the recommended treatment to replace the abnormal bone marrow stem cells and create a normal immune system.

Twenty-two-month-old Salsabil is the first child in the world to be completely cured of ADA-SCID using genetically altered stem cells. Salsabil is the third bubble baby born to her family, a member of Jerusalem's Arab community. The first died from the condition. Salsabil's older sister, Tasmin, survived after receiving an allogeneic cord blood transplant from a younger brother. After the first child died, Hadassah doctors froze umbilical cord blood cells from each successive birth for possible treatment of subsequent siblings.

In the early 1990s, scientists had already begun experimenting with altering T cells and stem cells through gene therapy. While scientifically successful, the experiments did not have a notable impact on the patient's condition because only a minute fraction of the genetically abnormal bone marrow products were repaired, Prof. Slavin said. The patients still required ADA replacement therapy to survive because the "good" cells were overwhelmed by the much larger number of genetically abnormal cells remaining in the host, he explained.

By the time Salsabil was born in February, 2000, significant advances had been made in the field of gene therapy and stem cell biology. Prof. Slavin determined that if he could give the genetically treated cells an advantage, they could prevail. Clinical application of these new concepts was offered to Dr. Claudio Bordigan, Head of the San Raffaele Institute, who made the ADA retroviral vector available.

After clearing all the legal issues, the groundbreaking procedure took place at Hadassah when the patient was seven months old. Salsabil received a mild treatment to suppress her abnormal stem cells, providing a biological advantage to the genetically corrected multi-potential stem cells and their products. Then, Prof. Slavin, his team and their Italian colleagues introduced the missing ADA gene into her purified bone marrow stem cells. No enzyme replacement therapy was given at any stage. The new procedure was uneventful and proved fully successful.

Within a few weeks the number of lymphocytes in the blood had risen dramatically and the toxic products in the blood, which would normally kill the lymphocytes, had declined. Within a month, Salsabil was out of isolation and went home in perfect condition, with no medications.

Nearly two years after the gene therapy, all her T cells and B cells, as well as other products of CD 34 stem cells, are genetically transduced and functioning normally. Interestingly, after exposure to chicken pox in the family, Salsabil's antibodies developed spontaneously and she did not develop any sign of the disease.

Since this first-of-a-kind procedure was performed, two other children have received a similar protocol from the Italian team, apparently with a similar success rate.

###

Founded in 1912, Hadassah, the Women's Zionist Organization of America is the largest women's, largest Zionist, and largest Jewish membership organization in the United States. In Israel, it supports the Hadassah Medical Organization, comprised of two hospitals that represent the most advanced treatment, research, teaching and rehabilitation facility in the Middle East. Since its founding, the Hadassah Medical Organization has been committed to compassionate care and treatment of all the resident of the region.

Prof. Shimon Slavin may be reached in on his cell phone Israel, which is 7 hours ahead of the U.S., 011 972 51 874-270 or by e-mail: slavin@huji.ac.il.

Disclaimer: AAAS and EurekAlert! are not responsible for the accuracy of news releases posted to EurekAlert! by contributing institutions or for the use of any information through the EurekAlert system.