The University of Cincinnati Neuroscience Institute’s mission has three components: patient care, research and education. The third part of that mission was on proud display this week as multiple neuroscience disciplines and centers of excellence staged premier lectures and presentations. From brain metastasis to multiple sclerosis to schizophrenia to rare movement disorders, the topics of the educational sessions were designed to intrigue and inspire clinicians, researchers and supporters to continue pressing forward in new directions at the UC Neuroscience Institute, one of four institutes of the UC College of Medicine and UC Health.
What do dandelions and brain metastases have in common?
Ronald Warnick, MD, Medical Director of the UC Brain Tumor Center, spelled out the problem of brain metastasis in stark terms at the fourth annual Wine Tasting Celebration at the Myers Alumni Center Tuesday night on the UC campus. This year, 170,000 people will be diagnosed with a brain metastasis in the United States alone, and the problem is increasing because people increasingly survive cancer. Whereas only 50 percent of cancer patients lived five years in 1975, 70 percent do so today. Lung cancer, breast cancer and melanoma are the most likely cancers to metastasize, or spread, to the brain.
Dr. Warnick explained brain metastasis with an analogy to seed and soil. Just as a dandelion’s seeds break away, blow in the wind and land in the soil, a lung or breast cancer’s cells break off and spread through the bloodstream and settle in another part of the body. And just as dandelions sprout anew in fertile, nutrient-rich soil, cancer cells take root as new tumors when they settle in the brain.
The source of nutrients, Dr. Warnick said, is healthy brain cells. With the help of funding generated by the 2012 Wine Tasting event, James Driscoll, MD, PhD, and his research team looked at how normal brain cells are providing nutrients to the invading cancer cells and causing uncontrolled growth, Dr. Warnick said. “A signal called micro RNA is stimulating the tumor cells to grow uncontrollably, while activating a force field that protects the cancer cells from chemotherapy. The result is a brain metastasis that is growing rapidly and is resistant to our common therapies.”
Dr. Driscoll’s next step was to introduce a suppressor that blocked that micro RNA signal, thereby preventing the cancer cell from receiving nutrients from healthy brain cells. This, in turn, caused the cancer cells to wither and die, like dandelion seeds that land on dry, barren soil. Dr. Driscoll is now testing the therapy in an animal model. If successful, it could lead to a phase I clinical trial for brain metastasis in early 2014.
Dr. Warnick closed his remarks by thanking the Brain Tumor Center’s supporters. “Your generosity and support last year allowed us to do this cutting-edge research, and your support tonight will allow us to take on the next promising avenue of research.”
What is plaguing our patients with rare movement disorders?
The Unusual Movement Disorders Marathon Symposium drew more than 150 neurologists, residents-in-training and experts from six countries Wednesday evening at the Cincinnati Club in downtown Cincinnati. The event was directed by Alberto Espay, MD, Research Director at the James J. and Joan A. Gardner Family Center for Parkinson’s Disease and Movement Disorders and a neurologist at UC Health.
During the symposium 12 professors each presented one of the most challenging cases of their careers, and a group of three internationally known specialists (pictured above) with no prior knowledge of the cases then discussed them and worked to arrive at the correct diagnoses and optimal treatment plans.
The heart-rending cases, illustrated by video, depicted once-healthy people struggling with ruinous symptoms that included cognitive decline, shaking, rigidity and freezing of gait. The cases were also staggeringly difficult, in some cases stumping the panel. They demanded knowledge of genetics, pathology, neurology and physiology, and they illuminated the profound difficulties that can confront a neurologist who is working independently.
Among these, there was a rare case of galactosemia and a singular case of “slowly progressive” rapid-onset dystonia parkinsonism (RODP). (Only 50 cases of RODP have been recorded since 1993.) There was a syndrome precipitated by legionella, the pathogen that causes Legionnaires disease. Another case presentation, which had bedeviled doctors at a leading center for four years, was just recently solved with an observation from a neurologist from another center.
The event, endorsed by the Movement Disorder Society and likely to be repeated in the future, was supported by educational grants from Merz, Ipsen, Allergan, USWorldMeds, Athena diagnostics, Medtronic and UCB.
What is the role of the hippocampus in schizophrenia?
Carol Tamminga, MD, Professor and Chairman in the Department of Psychiatry at the University of Texas Southwestern Medical School and a longtime leader in the field of schizophrenia, presented the 2013 Nasrallah Lecture Wednesday at UC.
Schizophrenia is a brain disease whose “bizarre and almost unbelievable symptoms,” in Dr. Tamminga’s words, have driven her quest to answer the question: “How can a brain do that?”
For the last 15 years she has focused her attention on the hippocampus, a small area of the brain that is “the size of your little finger” and that plays a role in synthesizing experiences into coherent memories. The brain has two hippocampi, one on each side, and within the hippocampi are “little stations that perform unique tasks and have unique functions,” she said. “We rely on the hippocampus, which is highly plastic, to learn something new.”
People with schizophrenia have alterations in parts of their brains, including the hippocampus, which appear to contribute to psychosis (hallucinations, delusions or other break from reality).
Dr. Tamminga and her team are examining hippocampal plasticity in schizophrenic psychosis with brain imaging and post-mortem tissue. They have found many things, including increased blood flow in one part of the hippocampus, a decrease in glutamate levels in another area and an elevated concentration of GluN2A, a subunit of the NMDA receptor, which ideally works like a good traffic cop in keeping brain signals flowing smoothly and efficiently but can become involved in several brain pathologies. Elevated GluN2A makes an area of the hippocampus “more susceptible to plasticity,” Dr. Tamminga said. “We speculate that it gets going too fast, makes mistakes, produces memories with psychotic content.”
Dr. Tamminga also noted that dendrites, the long, branching tails of brain cells that transmit stimuli to the cells, have smooth borders and occasional bumps in healthy brains but, in schizophrenic brains, are burdened “with a great clutter of stuff, a huge increase in spines.” These rough-edged dendrites produce super-sensitivity in part of the hippocampus, increasing the excitability of neurons.
The ultimate goal of her research, she said, is to translate these discoveries into new treatments for people who develop schizophrenia.
The Nasrallah Schizophrenia Lecture is made possible
by the Henry A. Nasrallah, MD, Endowed Lectureship Fund.
What is the role of T cells in multiple sclerosis?
Dr. Michael Racke, Chair of Neurology at the Wexner Medical Center at Ohio State University, discussed the role of T cells in multiple sclerosis at the annual Aring Lecture Wednesday at UC. “T cells are thought to be an important determinant in why some patients get MS and others do not,” explains Joseph Broderick, MD, Research Director at UCNI and the Albert Barnes Voorheis Professor and Chairman of UC’s Department of Neurology and Rehabilitation Medicine.
“In particular, Dr. Racke’s laboratory is examining the effect of micro RNAs that regulate gene function and changes in the T cell response, in both animal models and humans. This work could potentially lead to new, specific treatments for MS. In the meantime, this works provides some insights on how some of the medications we use for MS actually work.”
The Aring Lecture is named in honor of Dr. Charles Aring,
founder of the Department of Neurology at the University of Cincinnati College of Medicine.
— Cindy Starr