BASIC RESEARCH

The Cellular Neurobiology Laboratory conducts research on the mechanism and prevention of neuronal death induced by neurotoxins. We are particularly interested in toxic injury produced by chemotherapeutic agents. By understanding the mechanism of these toxic effects we are working to separate the harmful nervous system side effects from the primary role of the drugs in destroying cancer cells. Most of our work is carried out using tissue culture models of the peripheral nervous system. Specific techniques involve primary neuronal culture and culture of neuronal cell lines, light and electron microscopy, immunohistochemistry, protein biochemistry, in situ hybridization, reverse transcriptase-polymerase chain reaction, overexpression of specific genes using transfected plasmid vectors, down-regulation of specific gene expression using antisense oligonucleotide technology, and axonal transport studies.

CLINICAL RESEARCH

Clinical research activities involve both studying the natural history of peripheral nerve disease and bringing forward possible new treatments for peripheral or motor neuron disease. Current studies underway or planned for the near future include:

Current Studies:

• "Phase II Trial of IGF-I for Painful Neuropathy, IND 45,793" PI: Dr. A. J. Windebank.
• "Compassionate Use of 3,4 Diaminopyridine in Presynaptic Disorders of Neuromuscular Transmission" PI: Drs. C. M. Harper, Jr. and A. G. Engel.
• "Request to Contact Patients to Provide 30 ml of Blood to be Used in Establishing New Antibody Test" PI: Dr. A. J. Windebank.
• "Request to Harvest Routine Autopsy Material of Spinal Cord Specimens" PI: Dr. A. J. Windebank.
• "Treatment of Subacute Proximal Diabetic Neuropathy with IVIg BB-IND 6802" with Dr. A. J. Windebank.
• "A Treatment Protocol Using Myotrophin (Human Mecasermin [Recombinant DNA Origin]) Injection in Patients with Amyotrophic Lateral Sclerosis" PI: Dr. A. J. Windebank.
• "Dolostatin-10 for Phase II Advanced Renal Cell Carcinoma" PI: Dr. H. C. Pitot.
• "Phase I Trial of Suramin with Sequential Doxorubicin in Patients with Advanced Solid Tumors" PI: Dr. A. A. Adjei.
• "A Phase I and Pharmacologic Study of Sequences of Vinorelbine and Paclitaxel in Patients with Advanced Solid Tumors" PI: Dr. A. A. Adjei.
• "Cisplatin Neurotoxicity" PI: Dr. A. J. Windebank.
• "Measuring the Interobserver Reliability and Validity Between Different Medical Institutions of Maximal Voluntary Isometric Contraction Megascores (MVIC) and Manual Motor Testing Scores (MMT) in Assessing Progression of ALS" Co-Investigators: Drs. E. L. Feldman (University of Michigan, Ann Arbor, MI), J. R. Mendell (Ohio State University, Columbus, OH), H. Mitsumoto (Cleveland Clinic, Cleveland, OH), D. S. Newman (Henry Ford Hospital, Detroit, MI), E. J. Sorenson (Mayo Clinic, Rochester, MN), and A. J. Windebank (Mayo Clinic, Rochester, MN).
• "Suramin Neurotoxicity" PI: Dr. J. S. Gill.
• "Peripheral Neuropathy in Nondiabetic Patients with Hypertriglyceridemia" PI: Dr. C. M. Harper, Jr.

Future Studies:

• "Olmsted County Polio Study, 10 year Follow-Up Study" with Drs. E. J. Sorenson and A. J. Windebank.