Austin family helping to get NPC1 disorder onto newborn screening test
Four and a half years ago, Pam and Chris Andrews finally had an answer to the mystery of why their daughter Belle was having trouble walking, was falling down as many as six times a day and was experiencing some learning delays.
Just before her sixth birthday in March 2016, she was diagnosed with Niemann-Pick Type C1, a rare genetic disorder sometimes called childhood Alzheimer’s. Her sister, Abby, who was 2 at the time, also was diagnosed.
That began the Austin family's quest to find a treatment for their daughters and a way for other families to not have to wait so long for a diagnosis.
They went to the National Institutes for Health in Washington, D.C. Belle qualified for a research study for a new medication that needed to be administered every two weeks through a lumbar puncture. Abby qualified to receive this medication — hydroxypropyl-beta-cyclodextrin — by compassionate use because she was too young and not affected enough by the disease to qualify for the study.
The study meant that they would need to travel to Chicago every two weeks to Rush University Medical Center to see Dr. Elizabeth Berry-Kravis as part of the trial.
Pam and Chris Andrews, though, got to work. They first started lobbying Dell Children's Medical Center of Central Texas to become an approved site for the trial so they could stay at home and still have their daughters receive the treatment every two weeks. By that January, they were able to do so.
They started the Firefly Fund to raise money for research into children with NPC1, which usually has a lifespan of 10 to 15 years from diagnosis to death.
NPC1 is a lysosomal storage disease. Lysosomes are sacs of enzymes within cells that are like the body's recycling centers. They break up large molecules, then pass on the fragments to the rest of the body to break them down or send them back into the cell to perform their functions. In NPC1, cholesterol in brain cells cannot be moved to where it needs to go. This damages brain cells, which eventually die.
Children who have NPC1 usually experience clumsiness, shakiness of the hands and poor fine motor skills; problems with short-term memory, thinking and learning skills; hearing loss; problems swallowing; and trouble looking up with their eyes. They also might have seizures and eventually lose the ability to do schoolwork, talk and walk.
The Andrewses began meeting with other families and with researchers who study diseases like NPC1. They met Dr. Melissa Wasserstein, who is the chief of pediatric genetic medicine at the Children's Hospital at Montefiore in New York, at a national conference on genetic disease.
Wasserstein was doing research on adding genetic diseases into the newborn screening, known as the recommended uniform screening panel. It's that heel prick blood test done on babies while in the hospital. Each state has different guidelines, but many use the RUSP as their guide.
Wasserstein's new study, which launched this fall, looks at adding 14 different genetic diseases to the panel. NPC1 is one of the 14. The Screen Plus study expects to screen 175,000 newborns during a five-year period at eight hospitals in New York. The goal is to pick up just one case of NPC1 among the 175,000 babies.
Berry-Kravis, the Andrews girls' specialist in Chicago, says there's about a 1 in 100,000 chance of a baby being born with NPC1.
Even with that many newborns screened, there's a chance that the study won't identify any baby with any of the 14 diseases being tested for in Screen Plus.
If a baby comes back with a positive screening for one of the diseases, researchers will do additional tests to confirm the diagnosis to make sure it's not a false positive.
A previous study Wasserstein did on five other lysosomal disorders found about 20 kids in 65,000 with one of those disorders. Their doctors then were able to watch them closely and start whatever interventions were available.
To get on the RUSP, Berry-Kravis says they have to pick up a baby with NPC1, not have a high level of false positives, have treatments available and demonstrate that it makes a difference to start the treatment earlier. It also has to be an inexpensive test, which the newborn screening heel prick is.
"Once the RUSP recommends what goes on there, states are all supposed to do it, but there's a difference in the speed at which they get that done," Berry-Kravis says.
The Andrews girls are an indication of what can happen when early interventions are done. Abby started receiving hydroxypropyl-beta-cyclodextrin at age 2 and has very few symptoms now at 6, the age Belle was when she was diagnosed.
After about nine months of being on the study for hydroxypropyl-beta-cyclodextrin, it was confirmed that Belle had been in the placebo group when she was declining. She then was removed from the study and put on the real medication.
At 10, she has now stabilized and has even improved cognitively and in her swallowing.
"Abby has been a real source of information for them in terms of how and when to treat," Pam Andrews says. "She is lucky she had an older sister that paved the way. The earlier you diagnose, the earlier you treat, the better."
Abby is "the picture book of why you want to do a newborn screening" on NPC1, Berry-Kravis said. Abby runs around and goes to dance class and Belle has difficulty walking on her own. "We can make them all like Abby, even better," Berry-Kravis said.
Hydroxypropyl-beta-cyclodextrin does not have FDA approval yet, Berry-Kravis says, because the FDA did not find enough progression in the disease in the control group. The trial closed down, but the drug does have expanded access use. Berry-Kravis is still working on getting FDA approval, and more drugs are being tested as well for NPC1.
"None of these stop the disease," she says. "They just slow it down."
The Andrews family continues to raise money for their Firefly Fund and awareness.
"They have been really instrumental in pushing forward," Wasserstein said. "They are absolute leaders in this field and have really changed the landscape in newborn screening. They have been able to pull people together, so many different professionals, community members, to make this work. It's incredible."