image: A piece of large intestine, biopsied from a pediatric IBD patient, has been processed to reveal cellular and molecular features that can help scientists understand disease activity. These include epithelial cells (green), muscle (dark blue), T cells (lavender and purple), B cells (yellow), monocytes and macrophages (cyan), and cells that are actively dividing (red).
Credit: Jocelin Malone / Allen Institute
By Jake Siegel
Seattle, WA—May 13, 2024—With pediatric inflammatory bowel disease (IBD) diagnoses on the rise globally, a clinical trial in Seattle aims to transform treatment approaches through deep molecular profiling.
Recruitment has begun for the Seattle STRIDE study, a joint effort by Seattle Children’s Research Institute and the Allen Institute for Immunology. The trial aims to enroll 200 volunteers and follow them over three years. It will employ a range of genomic tools to analyze intact tissue samples from routine tests. These single-cell analysis methods will provide a detailed look at how the immune system behaves in patients with IBD and how it responds over time to specific drug treatments.
Deep immune profiling could offer an unprecedented view of the disease, paving the way for new and improved treatments, said Betty Zheng, MD, an assistant professor of pediatrics at Seattle Children’s and the study’s principal investigator.
“IBD is a very complex disease, and we only have a rough understanding of what is happening at a molecular level,” she said. “By partnering with the Allen Institute, we want to get a detailed view of the disease’s molecular mechanisms to find better ways of treating the patients we see in the clinic.”
Unraveling molecular mysteries
The exact causes and progression of IBD, a chronic inflammatory condition affecting the digestive tract, have remained elusive, Zheng said. It likely involves some combination of genes, immune dysregulation, and environmental and dietary factors.
In children, IBD is both more aggressive and harder to treat. Around 30% of pediatric IBD patients do not respond to initial treatments. Furthermore, nearly half of the remaining patients will find their treatments becoming ineffective over time. These children face risks like impaired growth, mental health issues, and missed educational and social activities.
A deeper molecular understanding of the disease could enable personalized treatment strategies, moving away from less effective one-size-fits-all approaches, Zheng said.
“Some children find relief with first-line therapies, others require a combination of treatments, and some don’t respond to anything and languish in the hospital for months,” Zheng said. “This is a big question mark in the clinic.”
A deep dive into the molecular workings of the disease could also uncover unknown pathways of inflammation. These pathways could potentially serve as targets for the development of new drugs. “There is a universe of information that is not being seen,” said Adam Savage, Ph.D., an Assistant Investigator at the Allen Institute for Immunology.
To explore that universe, Savage and other scientists will deploy a suite of advanced technologies refined at the Allen Institute for Immunology that can identify and pinpoint immune cells and molecules inside tissues collected during routine hospital visits. By analyzing patient samples over time, these tools can offer a window into how the disease progresses and how patients respond to treatment.
Behind the data and the advanced technologies, the ultimate goal remains clear: improving the lives of patients.
“We look at data on computers, or head into the labs, and we can get a little detached,” Savage said. “But when we visit and see the patients we’re trying to help, it’s a powerful reminder of why we come to work—to have a real impact on patients’ lives.”
Families interested in joining the Seattle STRIDE study can learn more here.
About the Allen Institute
The Allen Institute is an independent, 501(c)(3) nonprofit research organization founded by philanthropist and visionary, the late Paul G. Allen. The Allen Institute is dedicated to answering some of the biggest questions in bioscience and accelerating research worldwide. The Institute is a recognized leader in large-scale research with a commitment to an open science model. Its research institutes and programs include the Allen Institute for Brain Science, launched in 2003; the Allen Institute for Cell Science, launched in 2014; the Allen Institute for Immunology, launched in 2018; and the Allen Institute for Neural Dynamics, launched in 2021. In 2016, the Allen Institute expanded its reach with the launch of The Paul G. Allen Frontiers Group, which identifies pioneers with new ideas to expand the boundaries of knowledge and make the world better. For more information, visit alleninstitute.org
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