Keeping you up to date on recent headlines in neurology
Gene therapy trial to treat Alzheimer's underway at Georgetown ... Researchers in the Memory Disorders Program at Georgetown University Medical Center (Washington) are recruiting volunteers for a national gene therapy trial – the first study of its kind for the treatment of patients with dementia due to Alzheimer's disease. The phase II study examines the safety and possible benefits of CERE-110. CERE-110 contains a gene and is injected during surgery into a part of the brain affected by Alzheimer's disease. The gene will instruct brain cells to produce more of a protein, called Nerve Growth Factor, which helps nerve cells survive and function properly. "Our goal is to stop the progression of Alzheimer's disease," said Scott Turner, MD, PhD, director of Georgetown's Memory Disorders Program. "This is our first study of a gene therapy injected into brain, and thus the trial requires close collaboration with our neurosurgery colleagues at GUMC, in particular Dr. Chris Kalhorn." Turner said Kalhorn, an associate professor of the department of neurosurgery at Georgetown University Hospital, routinely performs neurosurgical procedures similar to the one being used in this study. About 50 people with Alzheimer's disease will participate in this study at fewer than 10 hospitals nationwide. Only persons with a mild form of Alzheimer's Disease, who are evaluated and deemed competent to consent for themselves, will be permitted to participate.
Concept acquisition in the human brain ... A new study explores how our brains synthesize concepts that allow us to organize and comprehend the world. The research, published in Neuron, uses behavioral and neuroimaging techniques to track how conceptual knowledge emerges in the human brain and guides decision making. The ability to use prior knowledge when dealing with new situations is a defining characteristic of human intelligence. This is made possible through the use of concepts, which are formed by abstracting away the common essence from multiple distinct but related entities. "Although a Poodle and a Golden Retriever look very different from each other, we can easily appreciate their similar attributes because they can be recognized as instances of a particular concept, in this case a dog," said lead study author Dharshan Kumaran, MD, from the Wellcome Trust Centre for Neuroimaging at University College London. While there is little doubt that humans form and use concepts all the time, not much is known about how conceptual knowledge is created in the brain or how it guides us to make efficient choices. It has long been suggested that the hippocampus, a brain structure critical for memory formation, plays a critical role in the acquisition of conceptual knowledge. However, thus far, there has been little concrete evidence to support this claim. Kumaran and colleagues designed an experimental paradigm that would allow them to track the emergence and application of conceptual knowledge. By using parallel behavioral and neural measures, the researchers found that a functionally coupled circuit involving the hippocampus and ventromedial prefrontal cortex underpinned the emergence of conceptual knowledge. Interestingly, however, it was the hippocampus alone that predicted which participants would be able to successfully apply the concepts they had learned to a visually novel setting. "What this suggests is that perhaps the hippocampus creates and stores these concepts, and passes this information to the prefrontal cortex where it can be put to use, for example in making choices where financial reward is at stake," said Kumaran.
New links between epilepsy and brain lipids ... In mice that are missing a protein found only in the brain, neural signals "go crazy," leaving the animals with epileptic seizures from a young age, researchers have found. The report, in Cell, details what it is that happens when the protein encoded by plasticity related gene-1 (PRG-1) gets lost, revealing an important fine-tuning mechanism for brain function. The researchers show that PRG-1's usual calming influence in the brain depends on its proper interaction with a particular class of lipids, known as lipid phosphates, which act as important cellular signals. The team led by Robert Nitsch of Universitätsmedizin Berlin speculates that changes in lipid phosphate signaling and PRG-1 function may be unrecognized causes of epilepsy. Nitsch and colleagues were the first to discover the new class of PRG proteins and were particularly intrigued by PRG-1's peculiar pattern of activity; it doesn't show up anywhere in the body or even anywhere else in the brain except on the receiving ends of one type of neuron. "Most molecules are more or less found in most cells," Nitsch said. "Some are more confined, but only a very few are confined to particular cell types in particular organs." In the new study they show that PRG-1-deficient mice develop very severe seizures due to changes in brain activity. Although the neural connections in the animals' brains appeared to be completely normal in their structure, they showed they were far too excitable. When PRG-1 was restored to individual neurons, activity levels returned to normal. That brain-tempering ability was lost when a portion of PRG-1 that interacts with the lipid known as lysophosphatidic acid (LPA) was altered. Animals lacking both PRG-1 and the LPA receptor didn't have epilepsy either, more evidence that PRG-1 acts via the lipid signal.
Immune response to spinal cord injury may worsen damage ... After spinal cord injury, certain immune cells collect in the spinal fluid and release high levels of antibodies. What, if anything, those antibodies do there is unknown. A new study by neuroscientists at the Ohio State University Medical Center (Columbus) may have solved the mystery. It found that the antibodies may actually worsen and extend the spinal cord damage. The antibodies first attach to nerve cells and other elements of the nervous system, then other components of the immune system attack the cells and substances marked by the antibodies as if they were infectious agents or foreign material. "Our findings suggest that inhibiting or depleting B lymphocytes, the cells that produce antibodies, may promote healing and reduce the long-term effects of spinal cord injury," said study leader Phillip Popovich, professor of neuroscience and of molecular virology, immunology and medical genetics and director of the Center for Brain and Spinal Cord Repair. "They may also help explain why the central nervous system does not repair itself efficiently and why other impairments often follow spinal cord injury." The animal study was published online by the Journal of Clinical Investigation. For this study, mice were anesthetized and given a moderately severe spinal injury that mimics a contusion-type spinal injury in humans. One group of injured mice had a normal immune system, with antibody-producing B cells. A second group of mice was identical to the first except that they lacked B cells, and therefore produced no antibodies. Nine weeks after spinal cord injury, the researchers compared the two groups. They found that, on average, the area of spinal cord damage in mice without antibodies was 30% smaller than the damaged area in mice with antibodies. They found that B cells and antibodies had accumulated around the spinal cord in the normal mice but not in the other group, and that antibodies had attached to damaged areas of the spinal cord.
Researchers find new bridge to blood brain barrier ... The blood brain barrier is generally considered an obstacle to delivering therapies from the bloodstream to the brain. However, University of Iowa (UI; Iowa City, Iowa) researchers have discovered a way to turn the blood vessels surrounding brain cells into a production and delivery system for getting therapeutic molecules directly into brain cells. Working with animal models of a group of fatal neurological disorders called lysosomal storage diseases, the UI team found that these diseases cause unique and disease-specific alterations to the blood vessels of the blood brain barrier. The scientists used these distinct alterations to target the brain with gene therapy, which reversed the neurological damage caused by the diseases. The findings, which were published in Nature Medicine's Advance Online Publication, could lead to a new non-invasive approach for treating neurological damage caused by lysosomal storage diseases. "This is the first time an enzyme delivered through the bloodstream has corrected deficiencies in the brain," said lead investigator Beverly Davidson, PhD, UI professor of internal medicine, neurology, and molecular physiology and biophysics. "This provides a real opportunity to deliver enzyme therapy without surgically entering the brain to treat lysosomal storage diseases. "In addition, we have discovered that these neurological diseases affect not just the brain cells that we often focus on, but also the blood vessels throughout the brain. We have taken advantage of that finding to delivery gene therapy, but we also can use this knowledge to better understand how the diseases impact other cell types such as neurons," Davidson added.
– Compiled by Rob Kimball, MDD