William Fahl

Education

BS, 1972, Zoology/Chemistry, University of Wisconsin-Madison
PhD, 1975, Physiology/Oncology, University of Wisconsin-Madison
Postdoctoral Research, University of Wisconsin-Madison

Title

Professor of Oncology
Cancer Control Program Member, UW Carbone Cancer Center

Research Description

The research in our laboratory is designed to enable cells to protect their genomes against toxic molecules, whether the toxins are encountered during cancer therapy, normal oxidative life, organ transplant or heart attack, or exposure to ionizing radiation. We approach this in two ways:

(I) design, synthesis and topical pharmaceutical application in cancer therapy patients of protective drug molecules to at-risk epithelial cells in oral mucosa, hair follicles, and skin. The concept and technology were first tested and developed in animal models and then in initial Phase I/IIa clinical trials. Significant reductions of oral mucositis (Integr Cancer Sci Therap 2018; 5(5):1-4) and radiation dermatitis (Radiation Oncol 2017; 12:201-208) have been shown in cancer patients in the first Phase IIa clinical trials. Further clinical trials to enable FDA approval of human drugs to prevent/suppress debilitating oral mucositis, radiation dermatitis and alopecia in human cancer therapy patients are ongoing and planned. To enable commercial development of these drug formulations, this technology is protected by a series of US and PCT patents (e.g. US 9,839,638; Compositions and Methods for Protecting Cells During Cancer Chemotherapy and Radiotherapy). Ongoing clinical and commercial development of these drugs is being done by NG Biomedicine ().

(II) invention, synthesis and systemic pharmaceutical administration of a new, immediate-acting, reactive oxygen species (ROS)-scavenger named PrC-210 to perfused transplanted organs or post-myocardial-infarct hearts or to healthy humans. PrC-210 protects the perfused organ/heart cells against ROS-induced ischemia-reperfusion injury or healthy humans against ionizing radiation encountered in many settings, e.g., 85 million CT scans per year (Radiation Res 2018; 190:133-141), nuclear spill or battlefield settings, or space travel. This technology has been developed in animal models and is being prepared for testing in Phase I/II clinical trials. PrC-210 reduction of kidney transplant ischemia-reperfusion injury to background in animals (Transplantation Direct 2019; 5:1-7) will now be tested in Phase I-II clinical trials to enable FDA approval of PrC-210, initially for suppression of “delayed graft function” in human kidney transplant. To enable commercial development of PrC-210, the technology is protected by a series of US and PCT patents (e.g. US 9,458,100; Synthesis and Growth Regulatory Activity of a Prototype Member of a New Family of Aminothiol Radioprotectors). Clinical and commercial development of the PrC-210 molecule is managed by a new company, NG Biomedicine – US, Inc. In both strategies (I) and (II), significant research is also done to optimize inventive pharmaceutical formulation and delivery of the active agent drugs to at-risk cell populations. This involves optimization of often conflicting elements of drug solubility, mammalian pharmacokinetics and metabolism/activation of prodrug forms to achieve pharmacologic efficacy in target cell populations.

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