Alumna Dr Sana Syed, MBBS ’07,* has won a grant from the US-based Crohn’s & Colitis Foundation in the US, CCFA, to study Crohn’s Disease, a poorly understood form of inflammatory bowel disease, IBD.
IBD, a chronic illness affecting the gut, has no cure and it affects an estimated 7 million people around the world who often have to undergo regular intravenous infusions or injections to keep the disease at bay and maintain their quality of life. These infusions are expensive as each dose costs between US $ 5,000 and US $ 10,000 and must be administered every four to six weeks. Often, if IBD is poorly treated, it can lead to even more severe symptoms or complications that could require surgical removal of the bowel.
Living with Crohn’s disease is a constant challenge as its symptoms include constant fatigue, regular abdominal pain and in cases with poor disease control, bloody diarrhea. “The disease’s symptoms are always on a patient’s mind and it governs many routine life choices that other people take for granted,” says Dr Syed, an assistant professor in pediatrics at the University of Virginia.
The study will see Dr Syed collaborate with Dr Lee Denson of the Cincinnati Children's Hospital Medical Center (CCHMC), one of twenty-eight centers whose collective efforts led to the launch of the study Risk Stratification and Identification of Immunogenetic and Microbial Markers of Rapid Disease Progression in Children with Crohn’s Disease (RISK), which is also funded by the CCFA.
RISK was a paediatric inception study cohort consisting of newly diagnosed children with Crohn’s disease who were prospectively monitored to assess how their disease was progressing. One critical insight from the study suggests categorising patients by their risk of facing different complications. This can inform the selection of the right type of therapy, known an anti-TNF therapy, to treat their type of disease. Dr Denson, one of the principal investigators of RISK, adds: "We found that there is a window of opportunity where anti-TNF therapy works better to prevent complications if started early after diagnosis. This has made precision medicine approaches to target the right therapy at the right time even more important."
This current grant will see Dr Syed and her team build upon these RISK findings to further study gut biopsies of children between the ages of 5 and 18 from a new RISK validation cohort at CCHMC. By using machine learning approaches developed by the team, they aim to extract distinct features from microscopic images when a patient was first diagnosed with Crohn’s Disease. The next step will be to correlate these features with each patient’s clinical and molecular data, or their genetic signatures, to see if they can identify which distinct subtype of Crohn’s Disease the patient is likely going to progress to.
“We know that Crohn’s Disease patients fall into distinct subtypes over periods of time which is why we have to tailor therapies for each group,” says Dr Syed. “Instead of using a stepwise approach of trialing different medication which is our current standard of care, we can then start developing targeted medications for that certain subtype.”
Through the study, Dr Syed and her team hope to develop precision medicine-based approaches to treat Crohn’s Disease. Precision-based approaches have led to improvements in treating a variety of diseases – such as certain types of breast cancer – where researchers have discovered the role of BRCA genes expression and have modified therapies to successfully manage and treat patients.
The use of big data in medicine has been an area of immense focus over the last few years and so has been developing leaders in data science and medicine. "Dr Syed is uniquely trained to lead a whole new generation of physician scientists who are using data and data analytics in new ways to create individualised care for patients. Her expertise in machine learning and Crohn’s disease allow her to develop these novel innovative approaches to patient care that are very likely to improve outcomes," says Dr Karen Johnston, director of the University of Virginia’s Integrated Translational Health Research Institute.
“Knowledge of IBD’s future phenotypic signature would be very valuable at the time of diagnosis,” says Dr Syed. “It could radically improve our clinical care by enabling patients to get the right therapy much faster and thereby avoid many of the disease’s painful complications.”
* Dr Syed also works as visiting research faculty in the department of paediatrics at Aga Khan University.