Targeting Abnormal Epigenetics in Diffuse Intrinsic Pontine Glioma by Inhibiting TET Enzymes
Abstract
More than half of active-duty military Service members are less than 25 years of age, and one of three active duty military members has children. The preponderance of young people and parents in the active-duty military means that pediatric and young adult brain tumors have a disproportionate impact on the health and well-being of military Service members and their dependents. This proposal will validate a potentially game-changing new approach to the most deadly form of brain cancer – diffuse midline glioma (also known when it occurs in the pons as diffuse intrinsic pontine glioma [DIPG]). This tumor kills 100% of the children and young adults who are diagnosed. Because this tumor has a biology that is different from brain tumors that affect older adults, we need to identify new therapeutic approaches. Current therapy for diffuse midline gliomas features radiation, which can extend life, but does not lead to cure. There is therefore a desperate need for new, innovative approaches to treat diffuse midline glioma and DIPG. The hallmark change in diffuse midline glioma is an alteration in the way the DNA of the cancer cell is organized. This change leads the cancer cell to have access to programs that should be used by other cells or at other times during normal growth and development. The openness of the DNA means that cancer cells look more like stem cells and have many of the characteristics of stem cells such as the ability to survive treatments such as radiation and chemotherapy. They can also migrate from one place to another (metastasis). Finding new drugs that can address this driver of diffuse midline glioma/DIPG is critical to improving outcome in a disease that disproportionately affects young people. This proposal will validate a novel target in DIPG that we believe is responsible in part for the abnormal organization of the DNA. We will develop a new therapeutic agent to disrupt this abnormal process. We will combining expertise from Johns Hopkins Oncology and Johns Hopkins Institute for Nanomedicine to develop a novel drug for this aggressive brain tumor. These “nanoparticles” address a potential drug that is administered through the bloodstream just to the brain tumor, with little systemic side effects. Our goal for this project is perform the preclinical testing that will justify moving this therapy into clinical trials. We hope to begin such trials within 5 years of the start date of this proposal (2 years to complete the studies in this proposal, 2 years to conduct safety studies in higher animas such as pigs, and then 1 year to obtain Food and Drug Administration approval for initial human testing). With support from the Idea Award, we anticipate that our innovative approach will lead to new, more effective therapies for diffuse midline glioma and DIPG, thereby improving outcomes for the militarily relevant populations of young adults and their dependent children.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810381
Entities
People
- Eric Raabe
Organizations
- Johns Hopkins University
- United States Army