UCLA researchers develop treatment for immune system disorder

Her 2-year-old son lay on the hospital bed with an IV in his arm. Wearing gloves and a mask, Jessica Ainslie gently patted his head as they waited for UCLA researchers to arrive with a potential cure for his disease – a syringe filled with his own genetically modified bone marrow.

Jessica Ainslie’s son Colton Ainslie was diagnosed in 2008 with severe combined immunodeficiency, or SCID, a rare genetic disorder that rendered him unable to form an immune system. For two years, her son was sheltered from the outside world, unable to play outside. Without an immune system, even a small cold could turn fatal.

“I didn’t know what (the disease) was,” Ainslie said. “The doctor told me not to Google it, but I did, and it was kind of frightening because all it said was that kids with SCID usually don’t live past the age of two … I was really, really scared.”

Last week marked the end of the UCLA stem cell and gene therapy trials on severe combined immunodeficiency, a rare genetic disorder. Years after his treatment in the UCLA trials, Colton is now healthy and enrolled in elementary school.

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When Jessica brought her newborn home from the hospital for the first time, she said he seemed healthy. But a few weeks later, Colton began having bouts of diarrhea and vomiting, and developed a rash in his esophagus, she said.

“We couldn’t take him anywhere when he got home (from the hospital), couldn’t have people over, and couldn’t even have him go outside,” Ainslie said. “You basically couldn’t do anything with him.”

“We couldn’t take him anywhere when he got home (from the hospital), couldn’t have people over, and couldn’t even have him go outside,” Ainslie said. “You basically couldn’t do anything with him.”

Realizing her son’s symptoms weren’t normal, Ainslie took him to the hospital. After a few months of continual hospital visits and tests, Colton was diagnosed with ADA deficiency-induced SCID when he was about 1 year old. He was then taken to the Children’s Hospital Los Angeles where Dr. Donald Kohn, a physician and now a professor in the departments of microbiology, immunology and molecular genetics and pediatrics, prescribed a treatment consisting of regular enzyme injections as a way to rapidly improve Colton’s condition.

The enzyme treatment seemed to work for a few months, but when Colton stopped progressing, Kohn introduced stem cell and gene therapy to try to cure his disease, Ainslie said.

When Ainslie’s daughter Abbygail was born in 2011, the family immediately tested her for SCID because Ainslie said she knew that her next child had a one in four chance of having the disease, since she and her husband are both carriers.

Abbygail’s results came back positive for SCID, and Ainslie took her to Kohn for the same stem cell and gene therapy that her brother Colton received.

Once the treatments were complete, Ainslie said she was able to do simple things with her children that parents with healthy kids might take for granted, like taking them to the grocery store.

“It was so fun, I felt like I had a newborn kid again,” Ainslie said. “Abby’s eyes were so big. It’s nice to see, because they don’t know the world.”

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Kohn began research on SCID in 1985. Over the next 29 years, he continued to conduct trials on the disease using stem cell and gene therapy techniques.

Kohn’s research focuses on the ADA gene, one of the many genes that can cause SCID. Typically, babies without immune systems do not live beyond one year unless they receive treatment, Kohn said.

The treatment involves first removing a sample of the patient’s bone marrow and infecting the stem cells with a virus that contains the normal ADA gene. The infected stem cells are then injected back into the patient, migrating to the bone marrow where they begin to form immune cells. The treatment involves only a single injection.

Though researchers around the world conduct trials with stem cell and gene therapy, UCLA is one of the main institutions using the treatment in the United States, Kohn said.

Before the technique was developed, doctors needed to find a suitable donor for a bone marrow transplant, which is often difficult and poses a risk of donor rejection with the patient’s antibodies attacking the donor’s cells, Kohn said.

Kohn’s first UCLA trial on SCID lasted from 2009 to 2012. Out of the 10 patient trials, nine had good recovery of their immune systems or were able to fight infections by making protective antibodies, Kohn said.

Currently, Kohn is working on another SCID trial that started in 2013, treating an additional eight kids in the same age range using a different virus. The treatment is not currently available to the general public.

Though the UCLA researchers have used this therapy on patients from three months to 15 years of age, it is more effective when the patients are younger because the immune system becomes fully formed in the first few months of life, Kohn said.

The treatment can also be used for other blood diseases, such as sickle cell disease and chronic granulomatous disease, said Kit Shaw, study manager for the trials.

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“When we start seeing (the babies’ immune cells form), and when they have a cold or something and get over it, you know that for (the parents) it’s very meaningful,” Shaw said. “It’s rewarding in that way to know that they can live normal lives.”

This year, Colton and Abbygail trick-or-treated around their neighborhood, wearing teenage mutant ninja turtle and princess Halloween costumes.

“They send me pictures all the time,” Kohn said, scrolling through his cell phone. “Here’s her two kids in their Halloween costumes,” he added, smiling.

Other researchers also said that seeing the effects of their work leaves a lasting impact.

Shaw said she realized how difficult it was for some parents to care for babies with SCID after moving to the clinical side of the research.

“When we start seeing (the babies’ immune cells form), and when they have a cold or something and get over it, you know that for (the parents) it’s very meaningful,” Shaw said. “It’s rewarding in that way to know that they can live normal lives.”

Shaw said she plans to continue working on trials for the treatment because of the effects she has seen on the families she meets.

“Sometimes when you’re stuck on the bench for a long time you kind of lose track of why you’re doing something,” Shaw said. “This is a constant reminder of why you do what you do.”