Sara and Paul McGlocklin knew something wasn’t right about their daughter Marian.
“By 9 months, she wasn’t crawling or even trying to. She wasn’t imitating our facial expressions. And, she no longer used some of her first words,” Sara said.
All of which, the McGlocklins reasoned, could be explained by Marian having been born slightly premature. But, just in case, they took her to Children’s Hospital of Los Angeles, where doctors discovered Marian had an enlarged spleen, a red flag for several serious genetic diseases.
In February 2017, DNA testing revealed 18-month-old Marian had Niemann-Pick Type C1 (NPC)—a rare, incurable, and fatal genetic disease diagnosed in only about 500 people worldwide, according to the National Neimann Pick Disease Foundation. Both Sara and Paul were unknowing carriers of the abnormal gene that causes NPC; the likelihood of both parents passing them onto their children was 1 in 4. (Their older daughter does not have NPC.)
NPC, which prevents the body from properly processing cholesterol, is sometimes called “Childhood Alzheimer’s” because those affected by the disease experience gradual neurological, cognitive, and physiological declines. As cholesterol builds up in the brain and other cells and tissues of the body, symptoms worsen. Most people with NPC die from complications of the disease within 10 years of their diagnosis, but become severely disabled much sooner.
“Unless there is a cure, Marian will lose her ability to talk, eat, walk, move, and remember us,” Sara said.
There are no FDA-approved treatments for NPC, but after reaching out to other families affected by NPC, the McGlocklins learned there was hope: a late-stage clinical trial of an experimental drug called VTS-270. Though VTS-270 is not a cure, it showed signs of slowing—though not reversing—the disease’s deadly path.
“This is the first drug treatment that’s shown the potential to alter the course of NPC and extend the kids’ lives,” Dr. Elizabeth Berry-Kravis, a pediatric neurologist at Rush University Medical Center, said.
Earlier studies have shown NPC disease progression is significantly slowed in children treated with the therapy, compared to historical patients who were not. It’s not known how long VTS-270 will work.
“The hope is that VTS-270 will put the brakes on the disease long enough to discover other treatments to help these kids,” Berry-Kravis said.
The trial for VTS-270 only admits patients who are at least 4 years old, so the McGlocklins and other parents of younger patients petitioned to be included in the study through a compassionate-use program headed up by Berry-Kravis. At the time, 2-year-old Marian was the youngest to start the treatment, which requires a bi-monthly injection into the spinal fluid.
Within months of beginning treatment, Sara says Marian “began to thrive.” “Before her first VTS-270 injection, Marian could not stand on her own. Now she’s cruising across the room.”
Still, Sara says, the family never forgets they are in a race against time and heartbreak.
“We were told that the younger the child when symptoms appear, the more aggressive NPC is,” Sara said.
She and her husband’s charity, Hope for Marian, is one of several family foundations that have banded together as part of SOAR, or Support of Accelerated Research for Niemann-Pick C disease. It’s a research initiative that unites families affected by NPC with scientists at Washington University in St. Louis, Albert Einstein College of Medicine in New York, and the University of Pennsylvania to quickly test potential new treatments for NPC in the research laboratory and move the most promising into clinical trials.
“The best shot of treating NPC is probably a combination of drugs, some of which will treat the symptoms and others that will go after the root cause of the disease,” Steven Walkley, professor of neuroscience at Albert Einstein, said.
Each family raises money in their local community and then pulls that money together to support priority projects that no single family could fully fund on its own. The scientists involved in SOAR collaborate too, communicating frequently, openly planning experiments and sharing data collection and analysis in real time, and working on the same pipeline of drugs.
“We don’t worry so much about taking credit for our work, we worry about finding something works and getting that to patients as quick as we can,” said Walkley.
Their goal is to create a drug “cocktail,” similar to those that pack a one-two punch to fight HIV.
Their approach has already seen success: Early laboratory studies of VTS-270 helped provided rationale for the study of the drug in people. Now, SOAR researchers have their sight set on gene therapy, which targets the defective gene that causes NPC to develop in the first place.
SOAR’s progress has given the McGlocklins and other families with NPC a real sense of optimism.
“It wasn’t that long ago that there was nothing to treat NPC. We’ve seen through this collaboration that science can move fast,” said Sara.
But will it be faster than her daughter’s disease?
“We really believe Marian will either be one of the last to die from or one of the first to be saved from NPC,” Sara said.