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News: December 2014

A look into some of the groundbreaking neurological breakthroughs from Partners' hospitals that will be featured at the World Medical Innovation Forum.

The World Medical Innovation Forum will highlight neurological breakthroughs from around the globe. Some of the most important ones are right here at the Partners' hospitals. Surgical Fusion At Brigham and Women's Hospital, surgeons in the Advanced Multimodality Image Guided Operating (AMIGO) Suite use the latest sophisticated imaging systems—PET/CT, ultrasound, magnetic resonance imaging, and fluoroscopy—so they can locate surgical targets in real time, clearly distinguish malignant from normal tissue to perform minimally-invasive image-guided neurosurgery. AMIGO, the $20 million brainchild of Ferenc Jolesz, MD, the Director, Division of MRI and National Center for Image Guided Therapy in Radiology at BWH and B. Leonard Holman Professor of Radiology at Harvard Medical School, opened in 2011 to offer a reduction in costs via enhanced surgical procedures. Since then, AMIGO has been used in more than 700 procedures. This first fully integrated operating suite to offer intraoperative access to the latest imaging modalities, AMIGO, consists of three interconnected operating theaters and various computerized scanning devices. The ceiling-mounted MRI glides from room to room. The multi-disciplinary teams of surgeons, radiologists, and biomechanical engineers can then match the technology to perform different innovative procedures. “Traditional surgery combines the hand and eye coordination of the surgeon,” says Dr. Jolesz. “But when a surgeon only has pre-op images to go by, the images can quickly become outdated due to the shifting of organs and tissues during a procedure. And when surgeons only rely on the naked eye when excising tumors, they will often miss a good portion of the tumor. With the AMIGO, we have replaced the surgeon's eyes with real-time imaging throughout surgery and have assisted the surgeon's hands with guidance devices, and eventually with robots.” Revolutionizing Alzheimer's Drug Discovery Due to the complexity of the brain and its protective blood-brain barrier, developing drugs is especially difficult especially for Alzheimer's disease. Four drugs are currently available for treatment of the brain-robbing ailment, but none works especially well. Amyloid plaque, a mixture of abnormal proteins and nerve cell fragments, and neurofibrillary tangles composed of a protein called tau, are hallmarks of Alzheimer's. Testing candidate molecules for Alzheimer's is painstaking, involving special mice with brain deposits of either plaques or tangles, and a year or more of waiting. That is all changing. Thanks to the recent work of Rudolph Tanzi, PhD, Director, Genetics and Aging Research Unit, Massachusetts General Hospital (MGH) and the Joseph P. and Rose F. Kennedy Professor of Child Neurology and Mental Retardation at Harvard Medical School, there is now a way to significantly accelerate the drug discovery process for Alzheimer's. Dr. Tanzi, along with his colleagues Doo Yeon Kim, PhD, and Se Hoon Choi, PhD, recently reported in the journal Nature that their breakthrough technology—dubbed “Alzheimer's-in-a-Dish”—can help Alzheimer's researchers go from the testing of a handful of drugs in mice per year to the testing of hundreds of thousands of drugs in a matter of months. Using special Petri dishes filled with human brain cells in a gelatinous three-dimensional environment, it's possible to develop both amyloid plaques and then the neurofibrillary tangles that are distinctive Alzheimer's signposts. In the course of developing his testing platform, Dr. Tanzi also put an end to a long simmering debate in the Alzheimer's research community: Was the amyloid really driving the creation of the tangles, and therefore the onset of Alzheimer's disease? To find out, Dr. Tanzi introduced a variety of drugs in his Petri dishes that stopped the amyloid plaque from forming. He discovered that it also stopped the tau tangles from being created. “This provided the first proof that stopping amyloid early on also stopped tangle formation, stopped cell death, and stopped the rest of the disease.” Dr. Tanzi believes that his cell culture model could make drug screening for Alzheimer's disease 10 times faster and 10 times less expensive. Using his Alzheimer's-in-a-Dish, he and his team are now running scores of tests with the 1,200 approved. 5,000 experimental drugs to see if they have any effect on amyloid production in the brain. “I always wondered how many of those drugs, either individually or together, would work against Alzheimer's disease,” he says. “In the past we just didn't know, because each test with a drug with a mouse model would take a year to complete. That's no longer the case.” New Movement on Treating Parkinson's Parkinson's disease affects more than one million people in the United States, with the annual cost to the economy of more than $14 billion. Caused by a loss of dopamine cells in the brain, scientists have dreamed for years of treating it by replacing those cells. Thanks to the recent stem cell work of Ole Isacson, MD, PhD, Director of the Center for Neuroregeneration Research/ Neuroregeneration Laboratories at McLean Hospital and Professor of Neurology at Harvard Medical School, we are getting closer to that reality. Dr. Isacson and his colleagues at McLean Hospital reported in the journal Cell Reports last June that they had successfully transplanted fetal tissue-derived dopamine-producing cells into the midbrains of adult patients with late-stage Parkinson's and that these cells remained healthy and functional for up to 14 years. These findings are critically important for the rational development of stem cell therapy for Parkinson's. Historically, there has been skepticism that transplanted dopamine cells could remain healthy without accumulating any significant toxic Parkinson's pathology. With this pivotal study, Dr. Isacson and his team disproved this notion. More importantly, the patients receiving the neuron boost no longer needed their dopamine replacement medication after the cells matured and took hold, about one year after transplantation. “Patients with Parkinson's usually get worse by 10 percent a year,” says Dr. Isacson. “If these study patients had continued without the cell transplants, they would have eventually been in wheelchairs. Instead, they were markedly improved and looked like young Parkinson patients with some deficits—and they were off drugs.” While study participants received harvested stem cells from human fetuses in a difficult and labor-intensive process, Dr. Isacson is now working to develop dopamine neurons from induced pluripotent stem cells (iPSCs), which are made from a patient's own stem cells and grown in the lab. “This will be very important in the quest for new Parkinson's therapies,” says Dr. Isacson.