On the Cutting Edge
Physicians affiliated with Mischer Neuroscience Institute and McGovern Medical School at UTHealth are engaged in a broad and intensive research program focused on the mechanisms, treatment and cure of neurological disease and injury. Recent efforts include the discovery of a genetic mutation linked to intracranial aneurysms, the use of chemotherapy infusion into the fourth ventricle for recurrent, malignant pediatric brain tumors, and a steerable telerobotic microcatheter for the treatment of stroke remotely.
Genetic Mutation Linked to Intracranial Aneurysms
A research team led by Dr. Dong Kim has discovered a genetic mutation linked to intracranial aneurysms (IA). After studying more than 500 people, including a large family with multiple incidents of IA, the team identified a specific protein coding gene, THSD1, whose mutation is suspected to lead to the formation of weak or thin spots in cerebral arteries. The defect can cause the artery to rupture, leading to bleeding in the subarachnoid space, which can result in disability or death. After pinpointing the mutation, the researchers investigated the consequences of a loss of function of THSD1, using genetically modified mice and zebrafish.
They discovered cerebral hemorrhage and increased mortality in both animal models when the gene’s function was switched off. In mice, the bleeding was located in the subarachnoid space, providing new insight and understanding into the function of a gene that has not been widely studied. The study results were published in the Nov. 17, 2016, issue of Stroke.
Studying a New Way to Deliver Chemotherapy
For the first time in humans, principal investigator David I. Sandberg, M.D., FACS, FAAP, and his team demonstrated in a previous pilot clinical trial that chemotherapy can be delivered directly into the fourth ventricle of the brain in children with recurrent, malignant brain tumors. Promising results from a pilot trial with low-dose methotrexate infusions has led to an ongoing Phase I dose-escalation trial. To date, seven patients with medulloblastoma have received methotrexate infusions. All patients had progressive disease prior to enrollment in the trial despite surgery, chemotherapy and radiation therapy.
Three of the seven patients had a partial response (at least 50 percent reduction in disease burden), two patients had stable disease, and two had disease progression. There were no serious adverse events or new neurological deficits caused by the methotrexate infusions.
Dr. Sandberg’s research has led to a new trial, recently approved by the FDA and about to open. In the new trial, two agents – methotrexate and etoposide – will be infused into the fourth ventricle simultaneously in patients with recurrent malignant brain tumors. The researchers hope for continued demonstration of safety and even more robust clinical responses. Dr. Sandberg is professor and director of pediatric neurosurgery and holds the Dr. Marnie Rose Professorship in Pediatric Neurosurgery in the departments of Pediatric Surgery and Neurosurgery at UTHealth.
Investigating a New Device for Treating Glioblastoma Multiforme
A research team led by neuro-oncologist Jay-Jiguang Zhu, M.D., Ph.D., associate professor of neurosurgery, continues its study of the effectiveness of the NovoTTF-100A device in treating glioblastoma multiforme (GBM), the most aggressive and common glial tumor. Historical data shows that median overall survival is 14.6 months with maximum safe resection followed by radiation and chemotherapies. A recent trial of triple chemotherapies plus TTFields demonstrated superior overall survival benefit compared to historical data: For patients who received a combination of thiotepa, busulfan and cyclophosphamide (TBC) plus TTFields at tumor recurrence, the median overall survival is 32.8 months.
For patients who received TTFields with standard of care or alternative therapy, the medial overall survival is 17.9 months.
Developing a Telerobotic Microcatheter
Daniel H. Kim, M.D., FACS, FAANS, and his fellow investigators are developing a steerable telerobotic microcatheter with life-changing potential for stroke patients worldwide. “Stroke is a time-sensitive emergency, and for those living in remote locations, access to fast care may not be possible,” Dr. Kim says.
“With telerobotics, an emergency physician in a rural community can access the femoral artery, and a skilled endovascular neurosurgeon working in a telerobotic hub can manipulate the microcatheter via computer to retrieve the clot.”
The first-of-its-kind endovascular telerobotic microcatheter-based robotic system is ready for testing in an animal model to prove safety before the researchers initiate a clinical trial.