Neurosurgery researchers receive NIH grants to study Parkinson's, stroke, brain cancer

Researchers from the Department of Neurological Surgery at Case Western Reserve University School of Medicine and University Hospitals Case Medical Center recently received multi-year, multi-million dollar grants from the National Institutes of Health (NIH) for studies in Parkinson's disease, stroke, and brain cancer.

Barry J. Hoffer, MD, PhD, adjunct professor of neurosurgery at Case Western Reserve and a member of the Department of Neurosurgery at UH Case Medical Center, received a 3-year, $1 million grant for continuing research into gliptins for the treatment of Parkinson's disease. Gliptins, widely used in the effective treatment of type 2 diabetes to safely regulate blood glucose levels, also have been found to provide neurological protection in Parkinson's. In rat studies, gliptins increase levels of hormones called incretins which reduced Parkinson's symptoms.

The new grant will enable Dr. Hoffer and colleagues to continue their evaluation of gliptins as a new treatment strategy for Parkinson's in mouse models.

"Currently, there is no cure for Parkinson's, and while medications can dampen symptoms, the drugs become less effective over time. Our research is part of an effort to find new strategies to protect nerve cells involved and to at least slow if not stop the degenerative process," said Dr. Hoffer.

Dr. Hoffer has served as the Scientific Director at the National Institute on Drug Abuse, part of NIH. He has made several seminal discoveries in Parkinson's disease since 1972. In his present position at Case Western Reserve, he studies animal models of neurodegenerative disorders (PD, stroke, trauma brain injury) and aging. His co-investigator on the new grant is Yu (Agnes) Luo, PhD, Xin Qi, PhD, from the Department of Physiology at Case Western Reserve University School of Medicine, and Michael Zigmond, PhD, at the University of Pittsburgh.

Yu (Agnes) Luo, PhD, assistant professor of neurosurgery at Case Western Reserve School of Medicine and in the neurosurgery department at UH Case Medical Center, is the principal investigator on a second 5-year, $1.7 million NIH grant, with co-investigators Dr. Hoffer and Nicholas Bambakidis, MD, professor of neurosurgery and director of Cerebrovascular and Skull Base Surgery at UH Case Medical Center.

Dr. Luo and her colleagues will investigate new methods of regenerating stem cells already present in the brain to heal the brain following a stroke. They will specifically look at small molecules that enhance the proliferation of and neuronal differentiation of these cells and evaluate their influences on stroke recover.

"Stroke is one of the leading causes of death and disability worldwide and places a heavy burden on the economy in our society," said Dr. Luo. "Current treatment strategies for stroke primarily focus on reducing the size of ischemic damage and on rescuing dying cells early after occurrence, which are often limited by a narrow therapeutic time window. However, the regeneration of the brain after damage is still active days, or even weeks after stroke occurs, which might provide a second window for treatment."

Eli Bar, PhD, assistant professor of neurosurgery at Case Western Reserve and in the neurosurgery department at UH Case Medical Center, was awarded a 5-year, $1.8 million NIH grant targeting brain tumor stem cells to learn more about why they are so resistant to conventional therapy. Co-investigator is Andrew Sloan, MD, who serves as the Peter D. Cristal Chair in Neurosurgery and director of the Brain Tumor and Neuro-Oncology Center at UH Case Medical Center.

The grant will focus on stem cells from glioblastoma, the most common and most deadly brain tumor that has a median survival of about one year despite maximal treatment. Drs. Bar and Sloan will specifically look at the role of the molecules MCT4 and Notch in the brain surrounding the tumors. Glioma stem cells are the cells which allow malignant brain tumors, considered incurable because they resist conventional treatment with chemotherapy and radiation. Drs. Sloan and Bar had been focusing on these molecules independently before Dr. Sloan recruited Dr. Bar to Case Western Reserve and UH Case Medical Center. Their study has three goals: To understand how Notch, a stem cell marker, is regulated by MCT4; to study the relationship between the two molecules in the region of the tumor that has low oxygen, and to understand how these molecules might inhibit radiation sensitivity.

"We hope that the results of this study will lead directly to better treatment of patients with these deadly tumors," said Dr. Bar.

Provided by University Hospitals Case Medical Center