The Helmsley Crohn’s Disease Program recently added a new strategic focus area. Can you expand a bit more about what the Disease Biology area will center on?
Our new Disease Biology focus area seeks to evaluate the biology underlying multiple facets of Crohn’s disease. With this broad approach, we hope to accelerate the improvement of patient care through multiple intervention points as we work towards a cure.
Variations in the human genome — differences in the DNA sequence between people — undoubtedly contribute to Crohn’s disease, with certain variants conferring higher or lower risk of Crohn’s disease. Yet, genetic risk alone does not tell the whole story, suggesting that other factors may contribute to disease. Evidence suggests that one important factor is gene regulation. The function of genes can be dynamically regulated, with no change to the DNA sequence itself, by modifying which genes are “on”, and therefore functional, in which cells. This process is influenced by environmental factors that are increasingly recognized as key players in Crohn’s disease. How exactly environmental factors imprint on biological processes to drive disease remains largely a mystery, and we are looking for how we might support promising research efforts that could build our understanding of this interplay.
A common, and particularly damaging, complication faced by patients with Crohn’s disease is fibrosis, or an accumulation of scar tissue in the intestinal wall. Fibrosis can lead to strictures, or narrowing, of the intestine, a complication that often requires surgery. Developing anti-fibrotic drugs has been historically challenging, and we hope that a better understanding of the molecular, cellular, and physiological pathways that contribute to fibrosis may ultimately point to new therapies.
Lastly, we think that there’s a lot we can learn from the study of other diseases — like lung fibrosis, or inflammation in other autoimmune conditions — so we’re excited to build a community with a variety of researchers, and to see if we can apply knowledge and methods from other conditions to Crohn’s disease.
Crohn’s disease is a complex condition including the immune system, the cells lining the intestine, and the microbiome. Each of these systems on its own is complex. At least 80 different kinds of cells have been identified in the human intestinal tract, for example, and how they interact and contribute to Crohn’s disease is still being investigated. Environmental factors are thought to contribute to disease development, but which environmental exposures influence the disease, and how they do so, is poorly understood.
Further complicating this picture, evidence suggests that Crohn’s disease may not be a single entity but a cluster of related diseases with similar presentation of symptoms. Indeed, known genetic risk factors for Crohn’s disease point to several different inroads to disease. Current therapies largely target one of these inroads, the immune system. The significant variability in how well patients respond to these therapies — from remission to hardly any improvement at all — further underscores the possibility of disease subtypes. By better understanding the biology underlying the disease, we hope to aid in the development of new diagnostic tools that can better identify disease subtypes, identify which therapies are appropriate for specific subtypes, and provide insight into new treatment modalities targeting other inroads to disease.
Ultimately, we hope to understand the biology behind disease initiation so we can prevent the disease from developing in the first place.
Philanthropy is in a unique position to support higher risk projects and novel ideas with potential for significant impact on patient care and outcomes. Helmsley is the largest private philanthropy focused on Crohn’s disease and this dedication means we can direct sorely needed resources to solve the complexities driving the condition. We seek to make smart investments in innovative research, to support promising ideas that simply might not be funded otherwise — always with the benefit of patients in mind. We are driven to improve the daily lives of people with Crohn’s disease.
Their work spans from determining how modifications in gene expression lead to Crohn’s disease, to teasing apart host-microbe interactions and their role in disease, to characterizing the underlying biology of perianal fistulas which are a devastating complication of disease.
Read more about the disease biology focus area, and check back for updates about our new grantees here.