A Potential New Drug for Pediatric Glioblastomas

Rheal Towner, Ph.D. Oklahoma Medical Research Foundation

Progress Update from 2nd year: 9/2012-8/2014

The Childhood Brain Tumor Foundation funded project, Novel Agent for Pediatric Glioblastomas (pGBMs), headed by Dr. Rheal Towner at the Oklahoma Medical Research Foundation, is assessing a novel agent, Oklahoma Nitrone 007 (OKN-007), in pre-clinical mouse models for pediatric glioblastomas (pGBs). Patient-derived cells, which have been passaged in nude mice, were obtained from Dr. Xiao-Nan Li at the Texas Children’s Cancer Center, and initially characterized by Dr. Towner’s group using magnetic resonance imaging (MRI) methods, such as contrast-enhanced morphological imaging to measure tumor volumes, diffusion imaging to measure structural changes, and perfusion imaging to measure vascular alterations. One particular cell line, TCCC-3752, was found to grow well in nude mice, and studies were initiated to assess the anti-cancer effect of OKN-007 in this model. Thus far, preliminary data indicates that OKN-007 is able to reduce tumor growth and increase survival in OKN-007 treated mice compared to untreated mice. More animals are currently being assessed to establish statistical significance. Immunohistochemistry has also been conducted to assess the anti-tumor effect on OKN-007 tumor growth markers such as apoptosis, cell proliferation and angiogenesis, as well as the transforming growth factor β1 (TGFβ1) pathway. Preliminary data at the moment indicates that OKN-007 is able to induce apoptosis. Other tumor growth markers are currently being assessed. Further studies related to the CBTF funded project will involve assessment of OKN-007 as an anti-pediatric glioblastoma agent in other pGB cell lines, in addition to repeating more animals with the TCCC 3752 pGB model. We are hopeful that OKN-007 will be considered as a potential new agent for the treatment of pGBs. Once we complete the pre-clinical studies, we will seek funding to conduct toxicity/safety studies in young animals, as a precursor to applying for an investigational new drug (IND) from the Food and Drug Administration in order to conduct clinical trials in pGB patients.

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