As of June 30, 1997, three research projects funded by the AANS Research Foundation were completed. On July 1, four new investigators started their funding period and two awardees entered their second year of research. July 1 also marks the conclusion of 14 years of research in the neurosciences made possible through the contributions of the neurosurgical community. For this we are very thankful. We are pleased to report on the work of those researchers concluding their Foundation-funded projects.
1996 Young Clinician Investigator
James M. Markert, MD
University of Alabama
Sponsor: Richard J. Whitley
Chairman: Richard P. Morawetz
Project Title: Mutant herpes simplex virus as a vector for IL-12 cytokine gene therapy of glioma
Project Update: Dr. Markert reports that engineered herpes simplex viruses have been effective in inhibiting malignant glioma growth and extending survival in experimental models. An HSV construct with IL-12 as a genetic insert is being engineered. This construct has several advantages:
- It utilizes the dual mechanisms of viral and gene therapy, which may provide a synergistic anti-glioma effect;
- Local production of IL-12 should minimize toxicity;
- Control of IL-12 expression via a doxycycline-responsive element provides an additional level of safety;
- IL-12 may promote anti-neoplastic effects despite glioma-mediated immunosuppression. There are plans to characterize this virus in an animal model in the near future.
1995 Research Fellow
D. Kyle Kim, MD
University of Washington
Harborview Medical Center
Sponsor: William Catterall, PhD
Chairman: H. Richard Winn, MD
Project Title: Protein-Protein Interactions and N-type Calcium Channel Function
Project Update: Dr. Kim reports that the N-type calcium channel, as well as the P/Q-type calcium channel, serves an important role in the regulation of synaptic transmission. A critical feature of calcium channel function are the protein-protein interactions with a variety of proteins of the synaptic core complex. This research project has shown that the N-type calcium channel and the isoforms of the P/Q-type calcium channel manifest distinct patterns of protein-protein interactions with these synaptic proteins and that the interactions may be regulated in part by ionic calcium concentration. Delineating these interactions may lead to new insights in the understanding of synaptic function of neurons.
1995 Research Fellow
John H. Sampson
Duke University
Sponsor: Darrell D. Bigner, MD, PhD
Chairman: Robert H. Wilkins, MD
Project Title: Evaluation of the Efficacy and Toxicity of Tumor-Specific Monoclonal Antibodies that Recognize a Variant of the Epidermal Growth Factor Receptor on Human Malignant Gliomas
Project Update: Dr. Sampson reported that antibody-mediated immunotherapy has been limited by a lack of tumor-specific targets. Antibodies that specifically recognize one of the epidermal growth factor receptor mutations that occurs frequently in malignant astrocytomas have been developed in the laboratory. The preliminary data has shown that these antibodies preferentially localize to subcutaneous tumors in vitro and are internalized by antigen positive cells. Such data predict that these antibodies may be powerful assistants in the delivery of cytotoxic agents to tumor cells that express this tumor-specific antigen.