‘Bubble babies’ get new immune system through novel gene therapy

When Jessica Ainslie had her son Colton, she knew there was something wrong.  Born prematurely, he weighed just 2 pounds, 9 ounces at birth, and he had to spend time in the neonatal intensive care unit before he could come home.

Thought to be out “out of the woods,” Colton then started developing breathing problems and was vomiting often, just a few months later.

“It just kept getting worse.  He wasn’t eating a whole lot, and he couldn’t keep anything down,” Ainslie, from Peoria, Ariz., told FoxNews.com. “We took him to the ER a couple times; they kept giving him fluids and sending him back home.  But I knew there was something wrong with my kid.  I had that mom gut feeling.”

Multiple blood tests were done on Colton, but nothing definitive came up.  Finally, one of Ainslie’s doctors said she was going to test for SCID, a possible diagnosis that made the new mom incredibly anxious.

For small children with severe combined immunodeficiency (SCID) – more famously known as ‘bubble boy syndrome’ – disease and infection are a constant source of worry due to a weakened, or almost non-existent immune system.  If left untreated, the condition is fatal in just one to two years.

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Sure enough, Colton’s blood work showed that he had ADA-deficient SCID, a form of SCID that affects 15 percent of SCID patients. While some treatments exist for those suffering from the disease, options are mostly limited to rare bone marrow matches or frequent drug injections that can last the entirety of the child’s life.  Though helpful, these treatments don’t always work and can come with terrible side effects and high costs.

Devastated by the diagnosis, Ainslie was offered some hope when she was asked if they could Air Evac 10-month-old Colton to Dr. Donald Kohn’s office at UCLA, one of the leading doctors in ADA-deficient SCID. Now, after having participated in a new gene therapy study developed by Kohn, Colton – and eventually his baby sister Abbygail –are living normal lives, nearly SCID-free.

‘Be their own donor’

Just about the time Colton was diagnosed, Kohn had been working on a novel gene therapy treatment for children with SCID.  In collaboration with researchers from both the University of California at Los Angeles and that National Institute of Health, Kohn and his colleagues have spent 11 years creating and testing this new therapy, which is capable of restoring immune systems in children with ADA-deficient SCID.

“What we’re doing with gene therapy is having the patient be their own donor,” study author Kohn, a member of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research at UCLA, told FoxNews.com.  “We insert the gene they’re missing and transport it back through their system.”

For Colton and other children who are ADA-deficient SCID patients, the blood stem cells in their bone marrow were unable to produce the enzyme adenosine deaminase (ADA).   ADA is a crucial ingredient for white blood cell production and survival.

“There are actually a number of different genes that can cause SCID,” Kohn explained, saying the immune system is similar to the blueprints of house – one gene goes missing and it all falls apart.  “ADA was the gene we worked with. It’s in all of our cells and the building blocks of DNA. However, if you’re missing that enzyme, the cells that are most affected are immune cells.”

The gene therapy they developed works by changing the chromosomal makeup of the blood stem cells – helping them to produce ADA, like other healthy cells. Kohn’s team cloned a normal version of ADA into a virus, which is somewhat produced like a typical drug.  The virus is then inserted into the bone marrow, where it takes hold and alters the DNA makeup of the blood stem cells.

Two groups of children were tested with this gene therapy.  In the first group four SCID patients were given the gene therapy by itself; while the antibodies in their system increase, their immune systems were not fully restored. So for the next six patients - the group Colton joined - the researchers first gave them a low dose of chemotherapy, which helped to ‘cleanse’ their marrow of the ADA-deficient blood stem cells.

“The chemotherapy drug carries off some of their own bone marrow, so the new bone marrow has more room to grow,” Kohn said. “The cells take in the body, and for several years, they are making new blood cells with the new ADA gene in them.”

After the chemotherapy was introduced, three of the six tested had their immune systems restored.  One of those three was Colton - paving the road to recovery for his soon-to-be sister Abbygail.

Catching Abby early

Ainslie was initially surprised at how easy the gene therapy experience was.  The virus was given to Colton in a simple syringe.  After two to three months of waiting, Colton’s antibodies finally went up enough so that he could return home – a happy change for Ainslie.

“[At the hospital] it was really restrictive,” Ainslie said.  “I had to wear a mask – I couldn’t touch him or kiss him. So we went home… and kept doing blood work here and sent them out to California.  Once he got to a certain level, he could start going out.  He’ll always have to have antibiotics, but at that point in time, he was the youngest for gene therapy.”

Meanwhile, Ainslie and her husband were mulling over another big decision – whether or not to have another baby.

“My husband and I thought about it,” Ainslie said.  “We had a one in four chance of having another with SCID.  I didn’t want to do it, but I wanted a little girl so bad.  So we tried one more time, and sure enough it was a girl.”

Not wanting to be blindsided again, Ainslie had her new daughter Abbygail tested right away.  At first, the nurse thought her blood levels looked fine, but Ainslie insisted on having her daughter’s blood tested for SCID – and the results came back positive.

Without hesitation, Ainslie had 3-month-old Abbygail entered into Kohn’s phase 2 trial of his gene therapy treatment.  This time, she was given a larger dose of chemotherapy than Colton had, along with the gene therapy.  According to both Kohn and Ainslie, you would never know Abbygail has a debilitating disease.  Her case goes to show how well gene therapy treatment for SCID patients works if caught early.

“Abbygail is 14 months today; she’s walking and talking and has a little attitude,” Ainslie said.  “She’s just a normal baby; you wouldn’t know she’s sick.  I’m kind of in denial with her.”

As for Colton, he’s starting kindergarten this year and really excited about school, Ainslie said.  While he doesn’t have the same amount of antibodies as his sister, Colton only needs ADA injections once a month instead of twice a week.

“If I didn’t do the gene therapy, they’d still be on shots for the rest of their life, and it costs so much money for one single vial,” Ainslie said.  “But now they get a chance at a normal life.”