Although our Precision Health Initiative (PHI) teams would prefer to be working as usual during this time, they are skillfully adjusting to the ever-changing conditions presented by the COVID-19 pandemic, while keeping an eye fixed toward future progress. We did a quick round up with the disease team leaders to see what research is still ongoing.
The Alzheimer’s Disease Drug Discovery (ADDD) Center work continues in several areas, as a number of the team’s first year goals are supported by computer- and discussion-based activities. These include evaluating new drug target opportunities to build the pipeline, virtual drug design for prioritized drug targets, constructing databases and computational tools, refining work processes and research plans, reaching out to potential collaborators, and evaluating new grant opportunities that leverage the ADDD Center’s capabilities and science. Alan Palkowitz, PhD, who leads the ADDD Center, says his team is anxiously awaiting the time when they can safely return to full speed and continue important work for patients.
Additionally, essential studies and mouse strains have been continuing in the Model Organism Development & Evaluation for Late-Onset Alzheimer’s Disease (MODEL-AD) consortium efforts thanks to the support from the partnering institutions, including IU School of Medicine, the Jackson Labs, and the University of Pittsburgh. This is especially important, given some decisions made by other institutions to euthanize mouse colonies in response to COVID-19, which will significantly stunt future research efforts. Bruce Lamb, PhD, and his colleagues are also interested in understanding the cognitive issues associated with COVID-19, given the most frequently reported symptom is loss of taste and smell.
According to Rafat Abonour, MD, leader of the multiple myeloma disease research team for precision health, the cohort study, led by Mohammad Abu Zaid, MBBS, has already enrolled more than 330 patients in the study, which is ahead of original projections. Researchers continue to collect bone marrow from already-enrolled patients. Additionally, efforts by Fabiana Perna, MD, PhD, Ken Cornetta, MD, and their colleagues continue to research and develop new vectors to hopefully someday – sooner than later – cure multiple myeloma.
The pediatric sarcoma team, led by Jamie Renbarger, MD, continues to advance ongoing research initiatives driving improved outcomes while changing the standard of care for pediatric and adolescent/young adult (AYA) cancer patients. The team is utilizing precision genomic sequencing, pre-clinical investigation in both genetically engineered mouse models (GEMM) and PDX (patient derived tumor cells implanted in humanized mouse models [xenografts]), and the use of systems pharmacology to provide data to support innovative approaches in pediatric cancer treatment.
The kinome profiling capability initiative is progressing collaboratively with the Peds Cancer Team, Proteomics Core and the Chemical Biology & Data/Informatics Pillars. The first tumor-adaptive response proteomics analyses have been completed by the Proteomics Core while Phase 2 PDX whole genome sequencing is now being conducted in the Medical Genomics Core.
The lab led by Karen Pollok, PhD, has substantially advanced innovative bioluminescence imaging (BLI) capabilities this past quarter and validated humanized intratibial/orthotopic models of osteosarcoma and Ewings Sarcoma, that are necessary for testing and developing better treatments and cures.
Wade Clapp, MD, and Steven Rhodes, MD, PhD, had a manuscript published in April of this year in the prestigious New England Journal of Medicine about the importance of whole exome studies and kinome evaluation to determine what is causing tumor resistance in certain children. The sarcoma team continues to expand their program, obtaining pilot funding through the Wells Center to collaborate with Mark Kelley, PhD, on the study of novel REF-1 inhibitors for treating relapsed pediatric sarcoma.
Triple Negative Breast Cancer
The triple negative breast cancer team, led by Bryan Schneider, MD, and Milan Radovich, PhD, is adapting to the challenges of COVID-19 with several different studies. One of the studies, Total Cancer Care, is now consenting virtually. It is a biobanking study enrolling all kinds of cancer patients, which started within PHI to facilitate no cost sequencing (DNA & RNA). They have focused it in triple negative breast cancer and the Precision Genomics Clinic, but are starting to work with other disease areas as well.
EAZ171, which is their study for African American women and neuropathy has enrolled 29 patients and is open at 339 centers across the country. Enrollment has slowed due to COVID-19, but is expected to pick back up as time goes on and pandemic restrictions get relaxed. The goal is to enroll 240 patients in this study.
The team is also moving forward on a new study called PERSEVERE, which is a follow-up to BRE12-158, during which the researchers discovered how to predict whether triple negative breast cancer will recur and which women are likely to remain disease-free. The research team plans to start enrolling during summer 2020.
Type 2 Diabetes / Gestational Diabetes
Recruitment is currently paused in the gestational diabetes studies, but the team has partnered with Heartland Studies to accelerate plans to launch e-consenting, virtual visits and remote collection of samples. Team leader David Haas, MD, says that while their enrollment numbers will be pushed back by a few months, the delays will not be catastrophic. His team is also incorporating COVID-19 into their studies. The new COVID-19 research will include testing what a positive diagnosis could mean during pregnancy, and what it might mean in terms of other COVID-19 exposures, such as the baby’s.
Haas has delivered several babies at Eskenazi Hospital who have tested positive for COVID-19. According to his observations, delivering the baby may help relieve symptoms such as shortness of breath, especially in the third trimester.