MRI Scan of Glioblastoma multiforme.
Glioblastoma multiforme (GBM) is one of the most medically challenging brain tumors, and can be fatal within one year.¹ Approximately 18,000 patients are diagnosed with GBM in the U.S., annually.² The current standard of treatment—maximal resection, followed by radiation with concurrent and adjuvant temozolomide chemotherapy has shown only modest improvement, with a median survival of 14.6 months, and a two-year survival rate of 26.5 percent.¹ “We need new avenues to improve survival rates,” says Assistant Professor of Neuro-Oncology Dawit Aregawi, M.D. He explains that Penn State Hershey Medical Center is conducting trials in immunologically-mediated therapy among the 90 percent of patients who experience tumor recurrences.³
While past GBM research has focused on chemotherapy, scientists have switched their focus to therapy utilizing the body’s own immune system to create tumor-fighting vaccines. Two upcoming phase 1 trials at Penn State Hershey, ICT-121 and WT2725, target cancer stem cells traditionally resistant to any form of treatment. Continue reading
Two major challenges of treating glioblastoma multiforme have been the type and location of these aggressive brain tumors.¹ Surgical tumor resection is difficult due to the widespread nature of gliomas. Chemotherapeutic treatments are often unable to cross the blood-brain barrier or cannot be confined to cancerous cells only, thus causing toxicity in normal tissue.¹ One viable option is targeted therapy, which can result in both improved chemotherapeutic and surgical results.
Research initiated by Achuthamangalam Madhankumar, Ph.D., assistant professor of neurosurgery at Penn State Hershey, has shown it is possible to use targeted nanovesicles to carry anti-cancer drugs or contrast agents selectively to tumor cells. The latter approach enhances tumor visibility, enabling the surgeon to more accurately assess the extent of the tumor. In addition, because of the unique expression of the interleukin-13 (IL-13) receptor on certain types of brain tumors, this targeted delivery system may be useful in the diagnosis of tumors.
The research used a murine model to test parameters including the efficacy of targeted versus untargeted liposomal doxorubicin, a chemotherapeutic agent.¹ Mice with intracranial tumors measuring five millimeters received fifteen milligrams of doxorubicin for each kilogram of body weight once a week.¹ Over six weeks, the size of the tumor decreased to less than one millimeter in the group receiving targeted liposomes, but did not decrease in the two of eight surviving mice receiving untargeted liposomes with doxorubicin.¹ There was a significant decrease in the tumor volume on contrast MRI images in the targeted liposome group, as seen in the figure.¹ Continue reading
In 2013, a paper published in Neurology advocated a clinical opinion that statin use was protective against Parkinson’s disease (PD).¹ However, Xuemei Huang, M.D., Ph.D., professor and vice chair for research, Penn State Hershey Neurology, led a team in a prospective analysis of the connection between statins and PD in the Atherosclerosis Risk in Communities (ARIC) study, which strongly suggests the opposite finding.²
While the analysis was based on just 106 cases of the more than 15,000 patients enrolled in ARIC, Huang says, “The length of the study, measurement of cholesterol, and recording of patients’ statin history all combine to make top-notch data collection.” One especially interesting feature of the ARIC patient cohort is that the study began before statins were widely used, but continued for twenty years, marking a unique opportunity to analyze pre- and post-statin disease correlates. In addition, not only did Huang’s study find that statins may not confer a protective effect against the development of PD, but they may actually increase the risk of developing PD with long-term use.²
The changes of statin usage (A) and plasma total cholesterol levels in Atherosclerosis Risk in Community Study (ARIC) stratified by statin usage (B) and Parkinson’s disease (C) status.2
The peripheral nerve program at Penn State Hershey Neuroscience Institute uses nerve transfer procedures to treat complex cases. Division Chief of Peripheral Nerve Surgery, Kimberly S. Harbaugh, M.D., explains one option, “Oberlin transfer is a procedure in which the clinician harvests part of one of the nerves from the hand and transfers it to the nerve in the patient’s bicep muscle. In this way, we have been able to restore significant levels of elbow flexion.” This has multiple potential applications, even in patients with spinal cord injuries. A portion of the nerves that are still intact above the level of the injury can be transferred to areas below the injury. In this way, spinal cord injury patients may be able to reclaim some finger and hand function, leading to improved self-care options.¹
Assistant Professor of Neurosurgery, Elias B. Rizk, M.D., M.Sc., details a recent case: “I had a male patient in his mid- 20s with a direct injury to his brachial plexus. He had been in a car accident, and in a state of semi-consciousness, he tried to release himself by using a pocket knife. He stuck it into his chest wall, severing one of the nerves to the arm. As a result, he lost his functional elbow movement. After six months, we elected to do an Oberlin nerve transfer to his bicep muscle. He had a very good recovery, with restoration of elbow flexion, and is now back to work.” Continue reading
Penn State Hershey Neuroscience Institute, has a global perspective when it comes to providing quality, multi-disciplinary care. This is best represented by the Institute’s expansive global exchange program among neuroscience clinicians and researchers, spanning four continents. Every neurosurgical resident is given the opportunity to hone his or her skills abroad, and almost half choose to do so. The primary exchange program is with the Bureau of Public Health in Tianjin, China, a formal relationship that began in 2006. Through a grant funded by Integra Foundation, eight Penn State Hershey Medical Center faculty members have studied there, while thirty-four exchange students have learned alongside Penn State College of Medicine faculty.
The exchange program functions as part of a developing program to encourage collaboration between clinicians and researchers at Penn State Hershey Medical Center and Tianjin’s largest hospitals. These reciprocal relationships enable providers to share best practices and advanced technology to improve patient outcomes. From a clinical standpoint, foreign physicians can gain experience with virtually every neurosurgical procedure that is currently performed at Penn State Hershey Medical Center. In the research arena, groundbreaking studies are being conducted through the Center for Neural Engineering and Penn State Hershey Neurosurgery laboratory. Research is ongoing in neurodegenerative disease, brain iron deficiency, brain tumors, epilepsy, and brain-machine interfaces. Physicians from the US and China also collaborate on clinical trials, mutually benefiting with shared data from their genetically disparate populations. Continue reading
Robert Harbaugh, M.D., professor and chair of Penn State Department of Neurosurgery and director of Penn State Hershey Neuroscience Institute, encourages all members of his department to take an active role in the field. “One thing we encourage in our residency training, aside from the usual missions of education, patient care, and research, is involvement in organized neurosurgery.” As they train new residents, Penn State Hershey Neurosurgery faculty members also encourage younger physicians to pass on their knowledge and adopt a citizenship role in the field.
Harbaugh himself holds multiple leadership positions, including president of the Society of Neurological Surgeons. He previously served as immediate past president of the American Association of Neurological Surgeons and director and member of the Advisory Council of the American Board of Neurological Surgery. Harbaugh has traveled extensively to lecture on various topics, including his clinical specialty of cerebrovascular neurosurgery and his research work on computer modeling of intracranial aneurysms.
Robert E. Harbaugh, M.D., FAANS, FACS, FAHA
Director, Penn State Hershey Neuroscience Institute
Distinguished Professor and Chair, Department of Penn State Hershey Neurosurgery
Professor, Department of Engineering Science and Mechanics
RESIDENCY: Neurological Surgery, Dartmouth Hitchcock Medical Center
MEDICAL SCHOOL: Penn State College of Medicine
UP TO 50 PERCENT OF BRAIN TUMORS RESISTANT TO STANDARD CHEMOTHERAPEUTIC AGENT TMZ
When a patient presents with a malignant glioblastoma, the current standard therapy is total resection surgery followed by radiation, either alone or in combination with temozolomide (TMZ) chemotherapy.1 Used to treat several types of cancer, orally-administered alkylating agent TMZ is known to inhibit cell reproduction by blocking the replication of DNA.2 Although it is less toxic than other alkylating agents, TMZ does not display efficacy in as many as 50 percent of brain tumors.3 Because of this, as well as the high rate of chemotherapy resistance in recurrent brain malignancies, there is an urgent need for new drugs for treatment-resistant tumors.4 Continue reading
ONE-OF-A-KIND FUNDING MODEL ALLOWS FOCUS ON TRANSLATIONAL RESEARCH
Data manager, Nicole Matthews shares information with Scott Simon, M.D., assistant professor of neurosurgery
Penn State Hershey Neuroscience Institute is home to the Office of Patient Oriented Research (OPOR), which facilitates neurological human trials research. Director, John Graybeal, explains that the OPOR acts as more than just an industry-sponsored clinical trials office, but also makes it possible for physicians to conduct translational research on existing data, with a focus on stroke, cerebrovascular disorders, and tumors of the central nervous system. The unique funding ratio of the OPOR—40 percent from industry, 40 percent from government, and 20 percent from within the department itself—is one key component of this ongoing work.
Robert Harbaugh, M.D., director of the Neuroscience Institute, elaborates: “The OPOR has facilitated substantial growth of multidisciplinary clinical trials in the treatment of cerebrovascular disease and brain tumors at Penn State Hershey Medical Center. The goals of the Neuroscience Institute, to foster interdisciplinary collaboration and support bench to bedside and bedside to bench translational research, are greatly enhanced by the work of OPOR.” Continue reading
Penn State Hershey Movement Disorders Center is home to a research study focused on the early diagnosis of Parkinson’s Disease (PD) and a program for measuring the efficacy of deep brain stimulation (DBS) treatment in advanced cases of the disease.
Associate Professor of Neurosurgery James McInerney, M.D., states, because PD symptoms can be mistaken for other disorders, an accurate PD diagnosis often does not occur until up to 80 percent of dopamine neurons have died. His colleague, Vice Chair for Research and Professor of Neurosurgery Xuemei Huang, M.D., Ph.D., leads a team that studies the dynamics of arm swing coordination during walking in both PD patients and controls, to identify any marked differences.1 Continue reading