Human Practices

Two-thirds of pancreatic tumors are in the pancreas's head and body, where surgery often leads to EPI which worsens malnutrition in cancer patients. Dr. Wadlow also expressed concerns about the current medication's affordability, side effects, and limited effectiveness. Using his feedback, we aimed to develop computational models to ensure our treatment delivered the required dosages within a desired timescale. Additionally, noting that chemotherapy patients should avoid probiotics due to infection risks, we plan to develop a cell-free treatment as a future iteration of our project.

We learned that nearly all cystic fibrosis patients suffer from EPI, leading to early prescriptions of PERT medications to prevent malnutrition and lung weakness. Current PERT medication is burdensome, requiring up to 30 capsules daily. Thus, our solution should aim to minimize pill burden on patients, potentially through implementation of a switch/inducible mechanism. Additionally, it is crucial to ensure that our enzymes are protected from degradation in the stomach, similar to the protective coating on PERT capsules. Lastly, we aim to develop a dairy-free yogurt, as they highlighted our oversight that yogurt is not always vegan.

Credentials: Emily Collins, Lauren Fay, Amanda Barber, Molly Seys, Sara Negron, Marion Irvin, Caitlin Benda, Kelsey Coulter, and Carrie Desai are all registered dietitians who are board-certified in oncology nutrition or nutrition support at Inova Schar Cancer Institute.

Dietitians have more hands-on involvement in EPI treatment than other medical professionals. The dietitians emphasized the importance of probiotic variety in diets, and thus encouraged us to consider a yogurt formulation that contains many types of probiotic bacteria. Additionally, they informed us that an enteric coating for our bacteria is not necessary as our bacteria will continuously produce enzymes and will be stable in the digestive tract. Most importantly, as dietitians have active involvement in EPI patientcare, they highlighted the importance of our device and indicated that they had many patients who are uncomfortable with current porcine-derived enzymes.

We learned that current medications are inaccessible to Dr. Strand’s patients due to high cost, as well as religious and ethical barriers. Additionally, patients with Alpha-Gal Syndrome may also react to this treatment. Dr. Strand affirmed that over-the-counter non-FDA approved alternatives to PERTS are ineffective and essentially “heated organ meat.” We determined that our target yield for one cup of yogurt is roughly 70,000-80,000 units of lipase, as this is the average amount required per meal. Lastly, Dr. Strand reiterated Dr. Ali's findings that hyperlipasemia is extremely rare, indicating that our goal to maximize lipase production poses minimal risk to patients.

In designing a preliminary model, they recommended reducing complexity by removing intermediates that do not directly affect downstream production. Instead of modeling every single molecule of every pathway, we can assume some constants. They also informed us of how to implement gradual degradation of molecules via thresholds instead of instantaneous off-switches using multiple events on MATLAB SimBiology. Their feedback and suggestions informed new iterations of our model; for example, they gave us the idea of incorporating the scaled degradation of a molecule following the activation of a repression event.