Therapeutics
The therapeutic goal in Crohn’s disease is to move individuals into remission as soon as possible and for as long as possible. One key challenge is that not every drug works for every patient, and some drugs can lose their effectiveness over time. Helmsley is committed to discovering new interventions and optimizing current therapies to induce and maintain long-term remission through a precision medicine approach — getting the right drug to the right person at the right time. Everything we do is focused on one question: what is best for the individual patient?
Our research grants are directed toward three therapeutic levers that we believe can achieve these ends – establishing immune homeostasis, addressing microbial dysbiosis, and promoting epithelial healing. Most existing therapeutics involve tamping down the aberrant immune response, and we support research to improve upon and optimize these immune-based therapies. Imbalance of the intestinal microbiome is known to play a role in Crohn’s disease; we support programs that further the understanding of microbial communities and that explore interventions to restore them to a healthier state. We are also focused on the epithelial barrier of the gastrointestinal tract by investigating whether epithelial disruption is a cause or an effect of Crohn’s disease and what treatments can be introduced to restore integrity of the barrier.
Throughout these efforts, we seek to translate insights from animal models to human clinical studies and to accelerate the time to market for novel and innovative therapeutics.
Finally, we acknowledge that our limited understanding of the underlying pathophysiology of Crohn’s disease hampers our ability to develop effective therapeutics. Helmsley is funding the creation of a Gut Cell Atlas, which is cataloging the many cell types in the small and large intestines, yielding insights into the molecular basis of Crohn’s disease and spurring new treatments. This effort is part of a global Human Cell Atlas, which is transforming what we know about human health.
Disease Process
The transition from a healthy gastrointestinal tract to active Crohn’s disease includes damage to the intestinal epithelium, an overabundance of immune cells at the site of injury, and an imbalance in the microbiome.
Image credit: SciStories
Cell-Based Therapies for the Treatment of Crohn’s Disease
One aim of the Crohn’s Disease Therapeutics pillar is to identify top researchers whose findings may lead to new medications for the treatment of Crohn’s disease...
McGill University’s Centre of Genomics and Policy Receives Funding to Create Ethics and Governance Resources for the Human Cell Atlas Initiative
New Policies, Tools, and Support to Enable Efficient, Ethical International Data Sharing for this Global Effort to Map All Cells in the Human Body
The Chan Zuckerberg Initiative (CZI), The Leona M. and Harry B. Helmsley Charitable...
Helmsley Grants UC San Diego $4.7M to Study Crohn’s Disease
Two grants aim to advance more personalized treatments for patients
Dr. Pradipta Ghosh, Soumita Das, Larry Smarr and Jürgen Schulze—researchers in diverse disciplines at the University of California San Diego—will aim to improve surgical outcomes and therapeutics for Crohn’s disease patients through $4.7 million in new grants from The Leona M. and Harry B. Helmsley Charitable Trust. Helmsley’s goal is to find a cure for Crohn’s disease, a long-term pursuit in parallel with improving patients’ lives today.
“UC San Diego is pursuing innovative ideas that align with Helmsley’s goal of advancing precision medicine for Crohn’s disease patients,” said Garabet Yeretssian, director of Helmsley’s Crohn’s Disease Program. “Researchers at UC San Diego are at the forefront of developing more individualized therapeutics for people with Crohn’s disease and improving lives.”
Crohn’s disease is a chronic inflammatory disease of the gastrointestinal tract, the symptoms of which include persistent diarrhea, internal bleeding and chronic pain. In the United States, 201 of every 100,000 individuals suffer from the disease, and these numbers are steadily rising. The incidence and prevalence of Crohn’s disease are increasing rapidly in developing countries, attributed largely to the swift modernization and westernization of society. There is an urgent need to prevent, diagnose early and reconcile the most effective and appropriate treatments for patients.
Transforming Crohn’s disease therapeutics
A $3.5 million grant will allow Ghosh, professor and director of the Center for Network Medicine at UC San Diego School of Medicine, and Das, assistant professor, chief scientific officer and director of HUMANOID Center of Research Excellence at UC San Diego School of Medicine to assemble a transdisciplinary team of cellular, molecular and stem-cell biologists along with computer science engineers, pathologists and gastroenterologists. Together, they will build and validate a stem cell-based “gut-in-a-dish” model of Crohn’s disease, as a “Phase 0” human model before clinical trials.
The stem cells will be derived from intestinal biopsies of patients with the disease and used to reverse-engineer the gut lining. The model will encompass the microbes, immune cells and other complex cell types found in the gut.
“This approach will help us to predict an individual’s response to therapeutics and, thus, personalize treatments—reducing the chances he or she will be prescribed a drug that won’t work or might have negative side effects,” said Ghosh.
“At present, there is no cure for Crohn's disease, and we believe our cutting-edge stem-cell based disease model will precisely identify effective treatment options, predict the outcome of clinical trials and provide the patients a high quality of life,” said Das.
3D medical imaging pilot to support surgical treatment
With $1.2 million in funding, a team of researchers from the California Institute for Telecommunications and Information Technology (Calit2) at UC San Diego will refine existing software used to translate two-dimensional (2D) medical imagery into interactive three-dimensional (3D) images that better reveal the common occurrence of strictures, narrowing and/or twisting of the small and large intestines, in Crohn’s disease patients.
Traditionally, surgeons rely upon radiologists’ readings of the 2D magnetic resonance imaging (MRI) and computed tomography (CT) scans to map out the digestive tract and treatment plan. However, the lack of detail can increase the probability that a patient will need to undergo several invasive procedures before medical professionals identify the most appropriate one. To support pre-operative planning, the team at UC San Diego will create a dynamic 3D model using the patient’s own MRI and/or CT 2D data. Results of this pilot project could improve surgical outcomes, as well as improve patient experience and understanding of the illness. With this enhanced knowledge, patients and surgeons can plan the most effective intervention based on their own unique anatomy.
“Our team developed the initial software to support my own surgical sigmoid colon resection in 2016. While working with my medical team using our one-off 3D representations of my colon, it quickly became evident that what was needed is a tool to enable doctors and surgeons to work routinely in the 3D reality of their patients,” said Larry Smarr, director of Calit2 and principal investigator on the project—and a Crohn’s disease patient himself. “Helmsley’s support will allow us to further develop the software and understand how its use can improve outcomes for patients.”
The pilot project brings together a unique cross-disciplinary team of doctors, surgeons, radiologists and computer scientists, including Jürgen Schulze, an associate research scientist with Calit2’s Qualcomm Institute and a leading authority on developing software for application of immersive virtual reality to medical situations.
“The software system we are going to develop, along with the entire data processing pipeline from MRI or CT image acquisition to a detailed 3D model of the colon, is going to allow surgeons to plan exactly what they need to do during surgery for Crohn’s disease patients. Our approach may well be applicable to other diseases in the future,” said Schulze.
‘Gut-on-a-Chip’ Research Aims to Find Personalized Treatment for Crohn’s Disease
To model human health and disease, organ-on-a-chip technology mimics the human body’s organ structure, functionality and physiology in a controlled environment. These miniature systems, which serve as accurate models of various organs from the heart and lungs to the gut and the kidneys, can use a patient’s own cells to test drugs and understand disease processes to help determine the right treatment for the right patient.
For 10 years, Hyun Jung Kim, a biomedical engineering assistant professor in the Cockrell School of Engineering at The University of Texas at Austin and assistant professor in the Department of Oncology in UT's Dell Medical School, has been developing organs-on-chips, specifically examining inflammatory bowel diseases and colorectal cancer. In 2018, Kim led the first study to determine how an intestinal disease develops using human organ-on-a-chip technology, confirming with his “gut inflammation-on-a-chip” system that intestinal barrier disruption is the upstream initiator of gut inflammation.
Now, thanks to a new $1.8 million grant from The Leona M. and Harry B. Helmsley Charitable Trust, Kim will apply his technology to better understand Crohn’s disease — an inflammatory bowel disease that can cause severe adnominal pain, diarrhea, fatigue and malnutrition. He and his research team will develop their Crohn’s disease-on-a-chip system to gain greater insight into what can cause and exacerbate the disease, with the goal of developing new treatments.
“I am humbled by the generosity of the Helmsley Charitable Trust,” Kim said. “I am also excited by the opportunity to help find answers to the root cause of a disease where much more research is needed.”
It is estimated that half of the 3 million Americans living with inflammatory bowel disease have Crohn’s disease. While the cause of the disease is currently unknown, doctors and researchers believe that genetic, immune and environmental factors contribute to disease onset and progression.
“Crohn’s disease is an extraordinarily complicated disease to figure out,” said Declan Fleming, M.D., an associate professor in the Department of Surgery and Perioperative Care at the Dell Medical School who will work with Kim on this project. “We believe this research can lead to a new tool to help us address the complexity of this disease. This could lead to improved treatments or possibly even to reverse the progression of Crohn’s disease altogether.”
Helmsley has made Crohn’s disease one of the top priorities in their focus on developing programs that improve life in the U.S. and around the world. With the number of people around the world affected by Crohn’s disease steadily rising, the organization sees an urgent need to prevent, diagnose early and reconcile the most effective and appropriate treatments for patients.
“There is a pressing need for more effective treatments for Crohn’s disease, and Helmsley is committed to finding more personalized options for patients,” said Garabet Yeretssian, director of Helmsley’s Crohn’s Disease Program. “This innovative ‘gut-on-a-chip’ technology has the potential to uncover triggers of Crohn’s disease, which will lead to improved therapies and ultimately better health outcomes.”
McGill University’s Centre of Genomics and Policy Receives Funding to Create Ethics and Governance Resources for the Human Cell Atlas Initiative
The Gut Cell Atlas
The Gut Cell Atlas initiative aims to catalogue the many cell types in the small and large intestines. The Gut Cell Atlas is part of the pathbreaking global Human Cell Atlas effort, which is transforming what we know about cells and their function in human health.