Israeli Procedure Helps Make Two Arab ‘bubble Babies’ Healthy

Dr. Shimon Slavin, a slim man with stick-straight white hair, holds two of his patients in his arms.

Tassnem Abu Said, 6, daintily kisses his left cheek, while her sister, Salsabil, 22 months, offers a slightly moister version on his right side.

“Shukran,” Slavin says in Arabic, thanking the two curly, dark-haired Israeli Arab sisters who scamper back to their father, Tahir, and mother, Hayam, sitting nearby.

As Salsabil toddles out of sight, her small red shoes take her over to the shiny metal elevator doors. Her father, Taher Abu Said, quickly darts over to scoop her up before her chubby fingers get caught in the elevator doors.

It isn’t unusual for toddlers to embark on search and explore missions. But a year and a half ago, Salsabil was living in a Hadassah hospital isolation unit, under the care of Slavin, who heads the bone marrow transplantation department at the Hadassah — Hebrew University Medical Center.

She and Tassnem were both “bubble babies,” born without immune systems, a genetic disease known as severe combined immunodeficiency. SCID is caused by the lack of an essential enzyme, adenosine draminase, or ADA, that creates a functioning immune system. Bubble babies are so named because the first patients diagnosed with SCID were isolated for prolonged periods in germ-free plastic tents.

Now both sisters have been cured of their disease — Tassnem with a bone marrow stem cell transplant and Salsabil by gene therapy, the “first in the world,” says her doctor, who worked with a team of Israeli and Italian researchers from the San Raffaele Institute in Milan, Italy, to develop a gene therapy procedure that can be used for every genetic disease caused by defective stem cells.

Stem cells are “blank cells” that can develop into virtually any kind of cell in the human body.

The “elegance” of this particular scientific advancement is how it unfolded within one family, Slavin says. It is also a story of Jews and Muslims, Israelis and Arabs, looking beyond the immediate conflict and trusting one another.

The Abu Saids were childless for 10 years, and desperately wanted children. When they finally conceived Ahmed, their first-born, he died within weeks because he had SCID-ADA and lacked a functioning immune system.

When Hayam Abu Said became pregnant again, the Abu Saids knew the disease was prevalent. As first cousins Hayam and Tahir’s fathers are brothers they had a “double dose” of this genetic disease, Slavin says. But as devout Muslims, they wouldn’t undergo prenatal diagnosis to detect whether the baby in utero carried the disease.

When Tassnem was born with the disease, the current treatment was ADA replacement therapy, an extremely expensive treatment that attempts to rescue the immune system and is only effective for one or two days at a time.

A bone marrow transplant from a matching donor is the preferred option, replacing the abnormal stem cells — the building blocks for all human tissue with normal stem cells to produce the missing enzyme.

Slavin used gene therapy to try and cure Tassnem of the condition. He took her own stem cells, and introduced the adenosine draminase replacement gene into her stem cells. The experiment was successful, allowing the gene to persist in her body for more than a year. But Tassnem remained immune deficient because the number of cells treated were few and ineffective compared with the overwhelming number of unhealthy cells still in her body.

At that point, Slavin could not follow up with enzyme replacement therapy, an enzyme booster shot that causes slow relief to the condition and is prohibitively expensive. Tassnem remained sick, but was kept alive.

Hayam Abu Said became pregnant again, refusing prenatal treatment, but gave birth to a healthy boy, Abdul Rahman, now 5, who was a successful stem cell match for his sister. Slavin took his bone marrow, isolated the stem cells, and transplanted them in Tassnem, successfully treating and curing her of the condition.

Another daughter, Yousra, was born without the condition. But a month and a half after Salsabil was born, Hayam Abu Said developed a sore throat and cough, and Salsabil immediately began coughing.

Since she wasn’t nursing the baby, Hayam Abu Said knew that Salsabil was showing signs of the autoimmune deficiency.

Unlike Tassnem, Salsabil had no bone marrow match among her siblings’ blood cells.

By the time Salsabil was seven months old, Slavin and his team of researchers had figured out how to give the genetically treated cells an advantage.

The Abu Saids were willing to give the treatment a shot, particularly given Slavin’s straightforward, honest appraisal of the experimental procedure.

“Dr. Slavin said he would do the same procedure if it was his daughter,” says Tahir Abu Said, 38, balancing Salsabil on his knee while cautioning Yousra, 4, not to open up the slim laptop computer sitting on the table. “So I told him to make sure he did it like he would do for his own child.”

Slavin not only followed through, but found funding to pay for the procedure. Tahir Abu Said is a pastry chef by training, who worked at Jerusalem’s King David Hotel before being laid off several months ago.

But even with an regular salary, the Abu Saids, who live in a two-bedroom apartment in Ras Al-Amud, an Arab neighborhood in eastern Jerusalem, couldn’t afford the cost of the gene replacement therapy on their basic health insurance plan.

As an experimental treatment, the family didn’t have to pay for the procedure, which was covered by Slavin’s research grant.

Slavin’s team had developed a protocol that would give the genetically coerced cells a biological advantage that would allow them to prevail in the patient’s field of stem cells.

He purified the stem cells and mixed them with a defective virus that wasn’t infectious but had the power to penetrate and infect the stem cells, introducing the adenosine draminase gene — the missing enzyme — into the nucleus and DNA of Salsabil’s stem cells.

“It’s like putting a computer chip into the body,” Slavin says.

After a few days of sitting in a culture, the virus-enriched, genetically altered stem cells were put into Salsabil’s body. Slavin also gave her a drug to suppress her sick cells and allow the new, healthy cells to develop and multiply for several days before encountering competition from the sick cells.

The healthy stem cells began developing rapidly and within weeks, Salsabil went home, without any fever or antibiotics.

The proof that her immune system was working came when all the other children came down with chicken pox and Salsabil stayed healthy because her body developed antibodies to the illness.

Nearly a year and a half later, Salsabil is an active, healthy toddler who runs to keep up with her three older siblings. She also has a younger brother, Ahmed, a healthy, eight-month-old baby named for his older brother who died of the disease.

“They’re all fine now,” Hayam Abu Said says.

As for Slavin and his team, they waited to announce the success of their treatment, making sure that the procedure was “solid and durable,” not “beginner’s luck,” he says.

They now have another patient undergoing the treatment, and are hoping the concept can be applied to all genetic diseases that require healthy stem cells. Salsabil, Slavin says, looking fondly at the active toddler, is “a model of gene therapy.”