With Risk Comes Reward Under the Microscope
Investing in the science that is poised to change lives.
Pushing Limits
Our new Chief Scientific Officer, Alan Moss, MD, explains how taking calculated risks is driving innovations that will improve patients’ health.
The Crohn’s & Colitis Foundation has played a role in every major breakthrough in inflammatory bowel disease (IBD). We’ve funded studies that paved the way for the development of infliximab (Remicade®) and adalimumab (Humira®), the first biologic drugs for IBD. Foundation-funded research led to the discovery of genes linked to IBD, including NOD2, the first gene ever associated with Crohn’s disease. And we’ve pioneered exploration of the gut microbiome by backing scientists who have generated knowledge through more than 70 scientific papers in leading journals in the span of about a decade.
Such achievements are only possible because of our willingness to delve into uncharted territory as we continue our quest for be er treatments and cures, says Alan Moss, MD, the Foundation’s newly appointed Chief Scientific Officer and a clinician-scientist who previously served as
“We fund researchers who come to us with novel ideas that align with our research goals and have strong potential to positively impact patients’ well-being.”
Director of the Crohn’s & Colitis Program at Boston Medical Center. Investing in such pioneering work entails taking some risks, but calculated ones. We carefully select projects that we believe will fill critical gaps in knowledge and address the most pressing patient needs.
“What is most exciting is that we are seeing the rewards of our investments, as several projects are translating into potential new treatments, diagnostics, and medical devices, which may lead to improved quality of life for patients,” says Dr. Moss.
Alan Moss
Our Goal: To Uncover New Biomarkers and Treatment Targets
The Payoff: Discovery of Novel Metabolites Linked to Crohn’s Disease
Funded by our Precision Nutrition initiative, Pieter Dorrestein, PhD, has been exploring the relationship between IBD and metabolites, which are chemical end products of the body’s and gut microbes’ metabolism. Most recently, he and his colleagues at the University of California, San Diego, used “reverse metabolomics” to search large datasets for the presence of metabolites unique to IBD patients. They ended up uncovering 139 novel metabolites, many of which are linked to Crohn’s disease. These findings were published in early 2024 in Nature (one of the most recognized scientific journals) and might one day be used to develop non-invasive diagnostic tests.
These newly discovered metabolites are bile acids, which are made in the liver and modified by gut microbes into many different molecules, and play a role in digestion and immunity. Dorrestein showed that several of these new metabolites could induce gut inflammation by altering immune cell function in Crohn’s patients.
Dorrestein’s team is now conducting a clinical study to confirm that his reverse metabolomics technique can accurately determine which foods a patient consumed by analyzing metabolites in their blood, urine, or stool. The study might also shed light on foods that correlate with disease activity.
Our Goal: To Limit the Side Effects
of Drugs to the Gut
The Payoff: Smart Pill Uses Reflected Light to Target the Colon
When IBD medications are administered orally, they are absorbed into the bloodstream, which may lead to side effects throughout the body. Thanks to a revolutionary new “smart pill,” effective oral drugs can be released right at the spot where they’re needed most, which minimizes systemic exposure.
With support from our IBD Ventures program, Biora Therapeutics developed a smart pill, known as NaviCap™. A er passing through the small intestine, it recognizes that it has arrived at the colon and releases the drug. “The capsule emits LED light, and it senses its location in the GI tract based on how the light is reflected back to it from the tissue,” Hurtado-Lorenzo explains.
The company is now conducting a phase I clinical trial in which NaviCap™ will be used to administer the drug tofacitinib to healthy volunteers. The goal is to demonstrate that delivering this drug in the colon will increase colonic tissue drug levels while reducing systemic exposure.
Our Goal: To Predict Risk of Stress-Related Flares
The Payoff: Evidence that Stress and Flares Are Linked
Many IBD patients say that psychological stress leads to flares, but until recently the evidence was purely anecdotal. Now, thanks to an investment via our Environmental Triggers initiative, we have proof of a clinical and physiological connection as well as a lead on how to stem this problem.
Our Goal: To Monitor Inflammation in Real Time
The Payoff: A Wearable Sensor that Measures Inflammatory Biomarkers in Sweat
Back in 2019, we identified non-invasive disease monitoring as a pressing but unmet patient need and awarded a grant from our Novel Technologies initiative to Shalini Prasad, PhD, a bioengineering expert at the University of Texas at Dallas. She’s since developed a wearable device, called IBD Aware (ibdwearable.com), that measures inflammatory markers secreted in sweat and sends the data to a smartphone app. Today, beta testers can actually purchase this groundbreaking piece of technology.
Research supported by the Foundation, including through an ongoing IBD Ventures investment, demonstrated that IBD Aware accurately measures TNF-a, IL-6, and C-reactive protein in sweat. (IBD Ventures is the Foundation’s funding mechanism that supports product-oriented research.) IBD Aware also accurately measures calprotectin.
“Never before has anyone tried and found a way to detect calprotectin in sweat,” says Andrés HurtadoLorenzo, PhD, Senior Vice President of Translational Research & IBD Ventures at the Crohn’s & Colitis Foundation. Ongoing research aims to show that IBD Aware remains effective when worn for longer periods in real-life se ings.
Using Foundation funding, Emeran Mayer, MD, of the University of California, Los Angeles, and his colleagues determined that about half of ulcerative colitis patients in their study experienced clinical relapse when exposed to stress, and that these individuals have high levels of two types of fecal microbes. Such alterations in gut microbiome composition and metabolite profiles could be further validated as biomarkers to predict flare risk in response to stress.
The researchers are also analyzing functional MRI data to identify brain changes related to stress and flares in these patients. “It’s a remarkable leap in connecting the dots,” says Hurtado-Lorenzo. Future projects could aim to determine whether stressreactive patients can sidestep flares by engaging in behavioral interventions like mindfulness or cognitive behavioral therapy.
Banking on the Newest Ideas
The Litwin IBD Pioneers program supports innovative, early-stage research with high potential to bring solutions to patients.
Funding any research project carries some degree of risk. Outside-the-box ideas are among the riskiest, yet at the same time they may have the potential to make a big difference quickly. That’s why the Litwin IBD Pioneers award supports scientists with novel concepts that have the potential to rapidly translate to patient care—even if preliminary data is sparse. By backing promising proofof-concept studies, we ensure that the best ideas don’t go unexplored.
Previous recipients of Litwin grants have made important discoveries that are helping us to be er understand IBD and eventually treat it more effectively. Past grantees have demonstrated the benefits of fecal transplants in ulcerative colitis and tested a novel drug delivery system that be er targets the gut. Learn more at crohnscolitisfoundation.org/litwin-ibd-pioneers.
Patients Embrace Innovation
IBD Ventures is bridging the gap between great ideas and tangible products to improve patients’ lives.
Scientific advancements o en require vast investments of both time and money, and many companies are reluctant to pour funding into early-stage work. Yet without adequate support, many early-stage projects that have potential to improve patient care would never see the light of day.
IBD Ventures is changing that. By directly investing in promising projects, we’re helping to bring products like the sweat sensor and smart pill to market (see page 3).
“I think I bring the perspective of a young and relatively new patient. I’ve had experience with taking several medications that have been wonderful for some people but not for me,” says John Makoweic, 27, an ulcerative colitis patient who works as a trader in the financial industry. He has served on the IBD Ventures Advisory Council since 2022. “Because of this, I see the need to work on more, be er, and diverse solutions for patients.”
Makoweic believes IBD Ventures is doing that in a meaningful way. Solutions like the sweat sensor and the smart pill show that there are different ways to address the disease to make people more comfortable.
“That bridge from academia to big pharma that IBD Ventures addresses is something that I find really exciting,” says Makoweic. “Being able to be exposed to new technologies coming down the pipeline gives me hope.”
Congratulations to Our Esteemed Grant Recipients!
The Crohn’s & Colitis Foundation is proud to have supported 20 scientists who have been named to the Clarivate 2023 Highly Cited Researcher List. This honor is awarded to researchers who have demonstrated significant influence, in part by authoring multiple papers that rank in the top 1% by citations globally in their field of study. Learn more at h ps://clarivate.com/highly-cited-researchers/.
John Makoweic
Our Next Breakthrough is in Your Hands
THE GAME-CHANGING PROJECTS described in this edition of Under the Microscope are just a few of the many ways we play a critical role in major IBD breakthroughs. We are working to redefine how scientists study IBD and accelerate the discovery of new and innovative therapies, offering real hope for people suffering with IBD. While our ultimate vision is a world without IBD, we’re equally commi ed to patients who are struggling with the physical and emotional toll of living with IBD right now—but we can’t do any of it without you.
Help us change the lives of those with IBD by making a gi to the Crohn’s & Colitis Foundation today. To make a contribution to the Crohn’s & Colitis Foundation, please visit crohnscolitisfoundation.org/microscope.
LEAVE A LEGACY OF GIVING
You can help strengthen the vision and commitment of the Crohn’s & Colitis Foundation by including the Foundation in your estate planning. As a member of the Founders Society, you will be listed in our Impact Report and receive inside information and updates on our mission advancement and research progress.
If you’re interested in making a planned gi or have questions regarding planned giving and the Founders Society, please contact Susan Carriker at scarriker@crohnscolitisfoundation.org .
Or visit crohnscolitisfoundation.org/freewill to access a free tool that will help you make a will in 20 minutes so you can easily leave a legacy gi to the Foundation.
Learn more at crohnscolitisfoundation.org
The Crohn’s & Colitis Foundation is the leading nonprofit organization focused on research and improving the quality of life for the millions of Americans living with inflammatory bowel disease (IBD). The Foundation has played a role in every major research breakthrough in IBD, bringing together best-in-class partners from around to globe to discover game-changing therapies. We are the trustworthy source for education, guidance, and support for IBD patients and caregivers, medical professionals, and the public.