Using patient-centered science against NF2
Olivia (name changed to protect her identity) was a high school track star. Her season started out strong, but as it progressed, things started to change. First, she started to occasionally feel dizzy. Then, she started to lose her balance. Within a few short months, Olivia could no longer walk straight.
What she and her parents didn’t know was that within her ears, small vestibular schwannomas – benign nerve tumors – were forming. These tiny tumors were causing Olivia’s dizziness, balance issues and walking difficulty.
As Olivia’s parents sought treatment for her, they found Dr. Steven Rhodes, pediatric oncologist at Riley Children’s Health, who diagnosed Olivia with neurofibromatosis 2 (NF2). It is a rare neurologic disorder that causes tumors (derived from malignant Schwann cells) to form on nerves that support balance and hearing. Currently, Olivia is one in 40,000 pediatric patients who are living with NF2.
Dr. Rhodes serves as the site principal investigator within the Neurofibromatosis Clinical Trial Consortium, a multi-institutional collaborative that includes organizations like Johns Hopkins University, Massachusetts General Hospital and Memorial Sloan Kettering Cancer Center. The group is dedicated to conducting clinical trials for the treatment of neurofibromatosis complications.
In 2021, Dr. Rhodes and Dr. D. Wade Clapp, chair of the Department of Pediatrics at the Indiana University (IU) School of Medicine, began working with scientists at the Indiana Biosciences Research Institute (IBRI) to research new treatments for NF2 patients. Together the scientists used high-throughput screening capabilities to identify drugs or drug combinations that could immediately proceed to Phase I/II clinical trials. Dr. Clapp noted, “We have identified one drug that informally is showing progress by reducing the number of surgeries, while also ensuring that the tumors in NF2 patients are stable or shrinking a little.”
As the year turned to 2022, Dr. Rhodes, Dr. Clapp and the IBRI team worked to accelerate their research. They did so with the help of Olivia, who agreed to provide blood samples that were transferred to the IBRI.
Now in the experienced hands of Bill Carter, senior research associate at the IBRI, Olivia’s blood cells are being reprogrammed into induced pluripotent stem cells (iPSCs) and then differentiated into Schwann cells that are uniquely representative of her disease. Once Carter has created a bank of Schwann cells, he will be able to test drugs and drug combinations in the lab, rather than having Olivia try different medications. The hope is to rapidly provide Olivia with improved options using existing medicines, and at the same time, learn more about the underlying disease so we can discover new therapies.
“We hope the iPSCs will help us personalize the therapy for each individual child going forward,” said Dr. Clapp. “And, as we look toward 2023 and beyond, we are collaborating with the IBRI to identify new chemical matter that will shrink NF2 tumors. Our patients are enthusiastic about having better drugs and so are we!