UCLA team cures infants of often-fatal “bubble baby” disease by inserting gene in their stem cells; sickle cell disease is next target

Poopy diapers, ear-splitting cries, and sleepless nights: sure, the first few weeks of parenthood are grueling but those other moments of cuddling and kissing your little baby are pure bliss.

The bubble boy.  Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

The bubble boy. Born in 1971 with SCID, David Vetter lived in a sterile bubble to avoid outside germs that could kill him. He died in 1984 at 12 due to complications from a bone marrow transplant. [Credit: Baylor College of Medicine Archives]

That wasn’t the case for Alysia and Christian Padilla-Vacarro of Corona, California. Close contact with their infant daughter Evangelina, born in 2012, was off limits. She was diagnosed with a genetic disease that left her with no immune system and no ability to fight off infections so even a minor cold could kill her.

Evangelina was born with Severe Combined Immunodeficiency (SCID) also called “bubble baby” disease, a term coined in the 1970s when the only way to manage the disease was isolating the child in a super clean environment to avoid exposure to germs. Bone marrow transplants from a matched sibling offer a cure but many kids don’t have a match, which makes a transplant very risky. Sadly, many SCID infants die within the first year of life.

Until now, that is.

Today, a UCLA research team led by Donald Kohn, M.D., announced a stunning breakthrough cure that saved Evangelina’s life and all 18 children who have so far participated in the clinical trial. Kohn—the director of UCLA’s Human Gene Medicine Program—described the treatment strategy in a video interview with CIRM (watch the video below):

“We collect some of the baby’s own bone marrow, isolate the [blood] stem cells, add the gene that they’re missing that their immune system needs and then transplant the cells back to them. “

Inserting the missing gene, called ADA, into the blood stem cells restores the cells’ ability to produce a healthy immune system. And since the cells originally came from the infant, there’s no worry about the possible life-threatening complications from receiving non-matched donor cells.

This breakthrough didn’t occur overnight. Kohn and colleagues have been plugging away for over twenty years carrying out trials, observing their limitations and going back to lab to improve the technology. Their dedication has paid off. As Kohn states in a press release:

“All of the children with SCID that I have treated in these stem cell clinical trials would have died in a year or less without this gene therapy, instead they are all thriving with fully functioning immune systems.”

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. [Credit: UCLA Broad Center of Regenerative Medicine and Stem Cell Research.]

Alysia Padilla-Vacarro and daughter Evangelina on the day of her gene therapy treatment. Evangelina, now two years old, has had her immune system restored and lives a healthy and normal life. [Credit: UCLA Broad Center of Regenerative Medicine and Stem Cell Research.]

For the Padilla-Vacarro family, the dark days after Evangelina’s grave diagnosis have given way to a bright future. Alysia, Evangelina’s mom, poignantly recalled her daughter’s initial recovery:

”It was only around six weeks after the procedure when Dr. Kohn told us Evangelina can finally be taken outside. To finally kiss your child on the lips, to hold her, it’s impossible to describe what a gift that is. I gave birth to my daughter, but Dr. Kohn gave my baby life.”

The team’s next step is to get approval by the Food and Drug Administration (FDA) to provide this treatment to all SCID infants missing the ADA gene.

At the same time, Kohn and colleagues are adapting this treatment approach to cure sickle cell disease, a genetic disease that leads to sickle shaped red blood cells. These misshapen cells are prone to clumping causing debilitating pain, risk of stroke, organ damage and a shortened life span. CIRM is providing over $13 million in funding to support the UCLA team’s clinical trial set to start early next year.

For more information about CIRM-funded sickle cell disease research, visit our fact sheet.

Disease in a Dish – That’s a Mouthful: Using Human Stem Cells to Find ALS Treatments

Saying “let’s put some shrimp on the barbie” will whet an Australian’s appetite for barbequed prawns but for an American it conjures up an odd image of placing shrimp on a Barbie doll. This sort of word play confusion doesn’t just happen across continents but also between scientists and the public.

Take “disease in a dish” for example. To a stem cell scientist, this phrase right away describes a powerful way to study human disease in the lab using a Nobel Prize winning technique called induced pluripotent stem cells (iPSC). But to a non-scientist it sounds like a scene from some disgusting sci-fi horror cooking show.

Our latest video Disease in a Dish: That’s a Mouthful takes a lighthearted approach to help clear up any head scratching over this phrase. Although it’s injected with humor, the video focuses on a dreadful disease: amyotrophic lateral sclerosis (ALS). Also known as Lou Gehrig’s disease, it’s a disorder in which nerve cells that control muscle movement die. There are no effective treatments and it’s always fatal, usually within 3 to 5 years after diagnosis.

To explain disease in a dish, the video summarizes a Science Translation Medicine publication of CIRM-funded research reported by the laboratory of Robert Baloh, M.D., Ph.D., director of Cedars-Sinai’s multidisciplinary ALS Program. In the study, skin cells from patients with an inherited form of ALS were used to create nerve cells in a petri dish that exhibit the same genetic defects found in the neurons of ALS patients. With this disease in a dish, the team identified a possible cause of the disease: the cells overproduce molecules causing a toxic buildup that affects neuron function. The researchers devised a way to block the toxic buildup, which may point to a new therapeutic strategy.

In a press release, Clive Svendsen, Ph.D., a co-author on the publication and director of the Cedars-Sinai Regenerative Medicine Institute had this perspective on the results:

“ALS may be the cruelest, most severe neurological disease, but I believe the stem cell approach used in this collaborative effort holds the key to unlocking the mysteries of this and other devastating disorders.”

The video is the pilot episode of Stem Cells in Your Face, which we hope will be an ongoing informational series that helps explain the latest advances toward stem cell-based therapies.

For more information about CIRM-funded ALS research, visit our ALS fact sheet.