Biobank, foundation team up to accelerate research into a rare disease

A Stanford “lending library” of biological samples and genomic information could accelerate diagnostic and therapeutic research for NGLY1 deficiency and related conditions.

- By Kris Newby

Kristen and Matt Wilsey started a foundation four years ago to support research into NGLY1 deficiency after their daughter, Grace, was diagnosed with the disease. The foundation has joined forces with Stanford to accelerate research into the rare gene defect.  
Carrie Chen Photography

Medical research is a numbers game: Funding often goes to those diseases with the largest number of patients. But what if your child is one of 36 born with a rare genetic disease?

In late July, the Grace Science Foundation and a clinical research team from Stanford University piloted a novel way to accelerate research into the rare NGLY1 gene defect. In just a few days, they collected health data and samples from 20 of the 36 living patients and members of their families, then cataloged them into a “lending library” of linked biological samples, genomic information and medical records. Now, any researcher interested in this or related defects can request access to this open-source data without the costs associated with patient recruitment, sample collection and biobanking.

The founders of Grace Science Foundation, Matt and Kristen Wilsey, started this nonprofit four years ago after their daughter, Grace, was diagnosed with this rare genetic disorder. It is inherited when both parents pass on a defective copy of the NGLY1 gene.

NGLY1 stands for N-glycanase 1. The gene tells the body how to produce an enzyme that removes sugar molecules called glycans from misfolded proteins so that the proteins can be used in key biochemical processes. When a person doesn’t produce enough of the enzyme, the process is severely disrupted. Shortly after birth, the affected individuals develop movement disorders, delayed growth, seizures, dry eyes and liver problems.

No time to wait

The Wilseys realized that Grace and the other individuals with NGLY1 deficiency could not wait the decades that it normally takes to find treatments for a newly discovered disease. Several patients have died before reaching adulthood. So, Matt Wilsey applied the strategy that he’d used as a tech entrepreneur building fast-moving startups in Silicon Valley: He assembled a team of experts, provided them with funding, then urged them to share findings early and often. By fostering trust and collaboration, scientists from different institutions could build on one another’s ideas more quickly, short-circuiting the many months that it takes to write up a study and submit it to journals for open publication.

Janine Sung and Rebecca Giessler make sure biological samples from the patients and members of their families are properly labeled, de-identified, processed and stored in a biobank at Stanford.
Kris Newby

Among the experts Wilsey recruited was Rohit Gupta, director of the biobank and clinical research services under Spectrum, the Stanford Center for Clinical and Translational Research and Education. At that time, Gupta was breaking in a new system for storing, tracking and sharing biological samples. He and Gupta brainstormed about how they could join forces and use the new biobank to speed up the slowest and most inefficient phases of any human-subject study: participant recruitment and sample collection.

Typically, it takes months to years for a researcher to find enough target patients from whom to collect biological specimens and data. (For many rare diseases, a researcher may never find enough patients to justify starting the analysis phase of a study.)

Through meticulous planning, the Wilseys and the Stanford team designed a streamlined process to collect biospecimens and health data in just a few days. Patient recruiting and logistics were orchestrated by the Grace Science Foundation and Shannon Rego, MS, a genetic counselor in the lab of Michael Snyder, PhD, professor and chair of genetics. Leveraging its communications channels, the foundation invited NGLY1 families to its annual scientific conference in July in Palo Alto, with the promise of meeting researchers face-to-face and participating in a study that might accelerate treatments and cures.

Once they arrived, Laila Craveiro, the nurse manager of the Spectrum clinical services unit, oversaw 18 nurses, phlebotomists, coordinators and physicians in collecting 325 skin, urine, stool, blood and DNA samples.

‘A challenging event’

“It was a challenging event,” said Craveiro. “Two children had seizures. Many were in wheelchairs. At the end of weekend, we were bone-tired but happy to be a part of this significant event.”

Before the collection event, the unit’s staff created color-coded labels to avoid mixing up samples of family members with the same last name. They had to line up couriers to transport time-sensitive samples to the biobank facility for processing in under an hour. And the Grace Science Foundation found volunteers to translate for the families who spoke Portuguese, German, French, Spanish, Danish, Hebrew and Chinese.

Back at the biobank, lab technicians went beyond standard specimen-processing methods to isolate and preserve cells and fluids from the collected samples. This centralized sharing approach also minimizes the error associated with the inherent variability in sample collection and processing methods. Each specimen was labeled with de-identified tags and logged into the biobank warehouse so that they could be retrieved as needed from a freezer array managed by Janine Sung, the Spectrum biobank officer.

Modern-day biobanks are critical to accelerating global efforts in precision health.

To accelerate analysis and discovery, the NGLY1 samples now can be requested by researchers through a web-based catalog hosted at Stanford. A governance board of Stanford and the Grace Science Foundation representatives reviews requests.

Researchers can search the catalog and request age-, sex- and condition-matched specimens for analysis. Ultimately, researchers will also be able to download de-identified clinical and assay data sets to apply new, advanced bioinformatics approaches to looking at this patient population.

At Stanford, Snyder will lead the genetic sequencing of each participant’s gut microbiome. Guangwen (Gavin) Wang, PhD, director of the Stem Cell Core Facility in the Department of Genetics, will grow an NGLY1 stem cell line from the tissue biopsies. And Gregory Enns, MB, ChB, professor of pediatric genetics, will be working with researchers from other institutions around the world to analyze the genomic, metabolic and health-questionnaire data. They will be looking for ideas for early diagnosis and potential treatments.

“This effort will make a huge difference not only for our understanding of this rare disease, but also for insights into other, more common disorders, because the NGLY1 enzyme is critical to normal cellular metabolism,” Enns said.

Another researcher who is working on understanding the biochemical mechanisms behind NGLY1 deficiency is Carolyn Bertozzi, PhD, professor of chemistry and ChEM-H faculty fellow. She is working on a study that suggests forcing an NGLY1 deficiency in a cancer patient may keep tumors from becoming resistant to certain treatments.

Wilsey and Gupta said they were so pleased with the way the NGLY1 event worked that they’d like to find ways to facilitate this approach for other conditions.

“This biobank is a tremendous step forward to curing NGLY1,” Wilsey said. “We can’t thank the Stanford team enough for their heroic efforts. We firmly believe what we did is the new model that other organizations can follow.”

“Modern-day biobanks are critical to accelerating global efforts in precision health,” said Gupta. “They link unique biological specimens to databases of associated clinical and assay data. This provides researchers with immediate access to cohort-matched samples, which ultimately advances biomarker research and future diagnostics and therapeutics.”

For questions about the biobank or getting access to NGLY1 samples, contact Janine Sung at

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