News Article | August 1, 2017
Molecules that help cells communicate with each other--called cytokines--might be the key to repairing diabetic nerve damage, according to a new study published in Experimental Neurology. Diabetes devastates nerve cells, which can lead to poor circulation, muscle weakness, blindness, and other painful side effects. The new study showed diabetic mice can't repair nerve cells after damage due to low levels of specific cytokines. In a mouse model of type 1 diabetes, researchers measured cytokine responses in mice with damaged sciatic nerves. Diabetic mice responded with unusually low levels of cytokines that notify other cells of injury, which in turn hampered activation of reparative genes. The results provide a new explanation for irreparable nerve cell damage seen in diabetic patients. Replenishing the missing cytokines could help improve symptoms for diabetics, said study lead Richard Zigmond, PhD, professor of neurosciences at Case Western Reserve University School of Medicine, "Our results indicate that targeting this cytokine pathway might alleviate some of the neural complications from diabetes." Zigmond added that pilot animal studies toward this aim are underway. Impaired cytokines in diabetic mice included those in the gp130 family--a group of molecules known to trigger extensive networks of cell signals. "Our findings are exciting because they show not only deficits of major gp130 cytokines in diabetic nerve tissue, but they also show changes in their downstream signaling pathways, namely the induction of certain regeneration-associated genes," Zigmond said. "These results provide a rationale for findings by others that gp130 cytokines can enhance peripheral nerve regeneration in animal models of diabetes." Until now, researchers weren't entirely sure why a boost in gp130 cytokines helped improve diabetic symptoms. Zigmond conducted the study with the help of co-first authors Jon Niemi, PhD and Angela Filous, PhD, both postdoctoral scholars at the medical school. The team is now working to see if the same mechanism of nerve repair is damaged during type 2 diabetes, and which types of nerve cells are involved. Said Zigmond, "Type 2 diabetes is a major problem worldwide and may or may not involve similar changes in cytokine expression." By understanding cellular mechanisms common to type 1 and 2 diabetes, the researchers may be able to design broad therapeutics that help reverse nerve cell damage associated with the disease. This work was supported by a Pilot Grant from the Juvenile Diabetes Research Fund and a National Institutes of Health grant DK097223 to R.E.Z. J.P.N was supported by training grants NS017512 and NS077888. J.A.L. was supported by F31NS093694. S.D.C. was supported by EY022358. For more information about Case Western Reserve University School of Medicine, please visit: http://case. .
News Article | July 25, 2017
Phase 1/2a Trial Will Set the Stage for Applications in Multiple Sclerosis, Stroke and Spinal Cord Injury SALT LAKE CITY, UT--(Marketwired - Jul 25, 2017) - Q Therapeutics, Inc., developer of clinical-stage cell therapies for central nervous system (CNS) disease and injury, announced U.S. Food and Drug Administration (FDA) allowance of its Investigational New Drug (IND) application to proceed with a Phase 1/2a clinical trial of Q-Cells® in patients with Transverse Myelitis™. TM is a crippling inflammation of the spinal cord that affects approximately 30,000 people in the United States, with more than 1,700 new cases diagnosed each year. Similar to Multiple Sclerosis (MS), TM destroys the myelin sheath surrounding nerve fibers in the spinal cord, compromising muscle control and affecting sensation. "This is another milestone in our quest to bring effective treatments for devastating CNS diseases and injuries to the clinic," said Steven Borst, the company's CEO and chairman. Clinical trials in the nine-person, dose-escalation TM safety study will pave the way to developing Q-Cells for treatment of several debilitating disorders caused by a lack of healthy glial cells. "Our approach uses the glial cell's natural ability to repair and support nerve cells in the CNS. Q-Cells hold great promise not only for those people with rare diseases such as TM and ALS, but for the many people worldwide who live with MS, spinal cord injury and stroke." The company also has FDA allowance to initiate a Phase 1/2a clinical trial in Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's disease). Q-Cells are human glial-restricted progenitor cells (GRPs) and the Company's first patented cellular therapeutic candidate. As reported in the May 2017 issue of Experimental Neurology, Piotr Walczak, MD, PhD, and his team at The Johns Hopkins University showed that Q-Cells exert a robust therapeutic effect when transplanted into the CNS of animals born unable to produce healthy myelin. The Q-Cells performed multiple repair and support functions resulting in myelination and restoration of animals to normal function with extended life span. These data, along with other published pre-clinical data from animal models of CNS disease and injury, show that delivering healthy glial cells into the brain and spinal cord can alter the course of currently incurable CNS conditions. "The FDA's clearance of this IND is yet another validation of our collaborative and purposeful approach to move Q-Cells into the clinic," said James Campanelli, PhD, Vice President of Research and Development at Q Therapeutics. "We developed this IND application leveraging our pre-clinical and therapeutic manufacturing experience, and achieved regulatory allowance in under a month. This approach will serve us well as we explore other disease indications for Q-Cells. We are grateful to all of our team members, academic collaborators and corporate partners without whom this step forward would not be possible." "We have long believed that Q-Cells' unique ability to repair and support CNS nerve cells is fundamental to treating many CNS disorders. The ability of these cells to replicate once injected, migrate, differentiate into mature glial cells and repair myelin, as demonstrated by Dr. Walczak's lab, further highlights the power of this therapeutic approach," said Mahendra Rao, MD, PhD, Q Therapeutics scientific co-founder and chief strategy officer. "We are eager to move forward with this trial and optimistic that Q-Cells will prove effective in treating human CNS injury and disease." Collaborative development of the Q-Cells therapeutic approach with Dr. Walczak and Nicholas Maragakis, MD of The Johns Hopkins University has received substantial support from the National Institute of Neurological Disorders and Stroke Translational Research Program (U01-NS06713) and the Maryland Stem Cell Research Fund. Q Therapeutics worked with MPI Research, Inc., to carry out preclinical safety studies, Goodwin Biotechnology, Inc., to manufacture the antibody used in cell purification, and Biologics Consulting Group for regulatory guidance. The company also partnered with the Cell Therapy and Regenerative Medicine Facility (CTRM) at the University of Utah in developing Good Manufacturing Processes to create the clinical-grade product. About Q Therapeutics, Inc. -- Headquartered in Salt Lake City, Q Therapeutics is a clinical-stage company developing adult stem cell therapies to treat debilitating central nervous system (CNS) disease and injury. The Company's first therapeutic product candidate, Q-Cells®, is intended to restore or preserve normal CNS activity by supplying essential nerve cell functions. Q-Cells may be suitable to treat a range of CNS disorders, including demyelinating conditions such as multiple sclerosis (MS), transverse myelitis ™, cerebral palsy and stroke, as well as other neurodegenerative diseases and injuries such as Amyotrophic Lateral Sclerosis (ALS, or Lou Gehrig's disease), Huntington's disease, spinal cord injury, traumatic brain injury, and Alzheimer's disease. Q Therapeutics' initial clinical targets are TM and ALS, with INDs in both indications now accepted to proceed by the FDA. The Company's proprietary product pipeline also includes neural cell products derived from induced pluripotent stem cells (iPSC). For more information, see www.qthera.com. Cautionary Statement Regarding Forward Looking Information -- This news release may contain forward-looking statements made pursuant to the "safe harbor" provisions of the Private Securities Litigation Reform Act of 1995. Investors are cautioned that such forward-looking statements in this press release regarding potential applications of Q Therapeutics' technologies constitute forward-looking statements that involve risks and uncertainties, including, without limitation, risks inherent in the development and commercialization of potential products, uncertainty of clinical trial results or regulatory approvals or clearances, need for future capital, dependence upon collaborators and maintenance of its intellectual property rights. Actual results may differ materially from the results anticipated in these forward-looking statements. Additional information on potential factors that could affect results and other risks and uncertainties are detailed from time to time in Q Therapeutics' periodic reports.
News Article | July 17, 2017
Congratulations to Professor Nick Fox, winner of the 2017 Weston Brain Institute International Outstanding Achievement Award. This £25,000 award recognizes an exceptional investigator who has made significant advances in accelerating the development of therapeutics for neurodegenerative diseases of aging through translational research, demonstrated remarkable leadership, and has a record of impeccable citizenship in the research community. This year's prize was provided by the Selfridges Group, and was open to researchers working in the UK. Professor Nick Fox has made outstanding contributions to the development of neuroimaging methods for the detection, differential diagnosis, and monitoring of disease progression in neurodegenerative dementias. The neuroimaging tools he developed have become the academic and industry standard for tracking brain atrophy in Alzheimer's disease clinical trials. Professor Fox has also made exceptional leadership contributions to the field at all levels, from catalyzing the creation of significant new research capacity and recruiting junior scientists in dementia research to effectively leading national and international collaborative projects to propel the field forward. He is a member of ADNI (Alzheimer's Disease Neuroimaging Initiative), an ongoing global effort to detect AD at its earliest stages and mark its progression through biomarkers, and a member of DIAN, the international Dominantly Inherited Alzheimer's Network. He helped establish the Leonard Wolfson Experimental Neurology Centre, the UK's first clinical research facility dedicated to neurodegeneration. He chairs the UCL Dementia Strategy Board and championed the concept of a dementia institute, contributing to the establishment of UK's Dementia Research Institute. He now directs the UCL Dementia Research Centre, a multidisciplinary hub for clinical research into various forms of dementia. Professor Fox is collegial, collaborative, and respects the contributions of others. He also devotes an enormous amount of time and effort to disease awareness and patient education, and chairs UK's Rare Dementias Support Group. In short, Professor Fox's work has had tremendous impact on translational research and therapeutic development for Alzheimer's disease and he is among the most highly respected investigators in this field internationally. The Weston Brain Institute accelerates breakthrough discoveries for the treatment of neurodegenerative diseases of aging, including Alzheimer's, Parkinson's and frontotemporal dementia. The Institute directly supports world-class neuroscience research and focuses on high-risk, high-reward projects that address the gaps in translational research using an innovative fast-track granting model. The Institute is supported by The W. Garfield Weston Foundation in Canada and the United States, and the Selfridges Group Foundation in the rest of the world. The Selfridges Group Foundation was set up by Selfridges Group Chairman W. Galen Weston to coordinate charitable and philanthropic activities within Selfridges Group. Selfridges Group consists of Brown Thomas and Arnotts in Ireland, Holt Renfrew in Canada, de Bijenkorf in the Netherlands, and Selfridges in the UK. As part of its philanthropic work, the Selfridges Group Foundation provides funds through the Weston Brain Institute to support medical research into treatments for brain disorders in Ireland, the Netherlands and the United Kingdom. The Foundation was first established in the 1950s by Willard Garfield Weston and his wife Reta, with a donation of shares from the family company, George Weston Limited. Today this business has grown into Canada's largest private sector employer with over 200,000 employees. The group of food retailing and baking companies includes not only the original baking division, Weston Foods, but also ACE Bakery and Loblaw Companies Limited. It is the success of these companies, the dedication of their employees and the loyalty of their customers that ultimately enables the Foundation to fulfill its charitable mandate. The Founders believed that as the funds were generated through the hard work and success of Canadian businesses, the grants should be given in Canada for the benefit of Canadians
News Article | August 16, 2017
Dr. Diamond studied the brains of nine stimulated rats and found that all of them had thicker cerebral cortices than their stimulus-deprived counterparts. “This was the first time anyone had ever seen a structural change in an animal’s brain based on different kinds of early life experiences,” she and Janet Hopson wrote in “Magic Trees of the Mind: How to Nurture Your Child’s Intelligence, Creativity, and Healthy Emotions From Birth Through Adolescence” (1998). The results, which Dr. Diamond, Dr. Rozenzweig and the psychologist David Krech published in 1964, helped change scientific understanding of the brain in fundamental ways. “Dr. Diamond showed anatomically, for the first time, what we now call plasticity of the brain,” George Brooks, a professor of integrative biology at Berkeley, told the university’s news service last month. “In doing so she shattered the old paradigm of understanding the brain as a static and unchangeable entity that simply degenerated as we age.” Dr. Diamond went on to show that brains can continue to develop through life; identified structural differences between male and female animal brains; and, by testing elderly players at a women’s bridge club, found that complex card play stimulated the body’s immune system. In one of her most celebrated studies, Dr. Diamond and her second husband, Dr. Arnold Scheibel, the director of the brain research institute at the University of California, Los Angeles, examined four samples from Einstein’s brain. The brain had been spirited away and preserved for decades by Thomas Harvey, the pathologist who performed Einstein’s autopsy in 1955. Dr. Diamond’s specimens arrived by mail in a jar formerly containing Kraft Miracle Whip and looked like “little sugar cubes,” she told The Washington Post in 1985. Dr. Diamond looked through a microscope and compared stained slices of the samples with brain tissue from 11 former patients at a Veterans Administration hospital. She found that one area of Einstein’s brain — the lower parietal lobe, associated with higher-level mathematical and language functioning — had a high concentration of glial cells, which cushion and feed neurons. The findings, although headline-grabbing, were inconclusive. “Many idiots have big brains loaded with glial cells,” Janice Stevens, staff psychiatrist at the neuropsychiatry branch of the National Institute of Mental Health, told The Post. Later research by other scientists, however, showed that glial cells play a hitherto unsuspected role in brain chemistry, helping to build connections between neurons and promoting more complex brain structure. Marian Cleeves was born on Nov. 11, 1926, in Glendale, Calif., and grew up in nearby La Crescenta. Her father, Montague, was a doctor who had emigrated from Yorkshire, England. Her mother, the former Rosa Marian Wamphler, was a former Latin teacher who cut short her doctoral studies at Berkeley to raise her six children, of whom Marian was the youngest. Marian saw her first human brain at 15. She had been accompanying her father on his hospital rounds when, through an open door, she caught sight of four men in lab coats standing around a table. “I have no idea what they were doing, but the sight of that brain, which formerly had the potential to create ideas, was embedded in my brain forever, as clearly as if it were yesterday,” she wrote in her autobiographical essay. “The thought was mesmerizing that that brain represented the most complex mass of protoplasm on this earth and, perhaps, in our galaxy.” As a professor of integrative biology at Berkeley, she was famous for carrying a preserved brain to her anatomy lectures in a flowered hat box. She had enrolled at Berkeley after attending Glendale Community College for two years. At Berkeley, she earned a degree in biology in 1948 and a master’s degree in anatomy a year later. She received a doctorate in anatomy in 1953, writing her dissertation on the hypothalamus. In 1950 she married Richard M. Diamond, later a renowned nuclear chemist at the Lawrence Berkeley National Laboratory. The marriage ended in divorce. In addition to her son Richard, she is survived by another son, Jeff; two daughters, Ann and Catherine Diamond; and five grandchildren. Dr. Scheibel, her second husband, died in April. Dr. Diamond accepted a position as lecturer at Berkeley after teaching at Harvard, Cornell and the school of medicine at the University of California, San Francisco. She retired three years ago. A documentary, “My Love Affair With the Brain: The Life and Science of Dr. Marian Diamond,” was broadcast on PBS in 2016. In 1985, the same year her paper “On the Brain of a Scientist: Albert Einstein” appeared in Experimental Neurology, Dr. Diamond published findings of an experiment with older rats — the equivalent of about 75 years old in human terms — that had been placed in a stimulating environment. After six months, they showed a thickening of the cortex, a sign that the brain cells had become larger and more active. In other words, the brain could grow and prosper, even in old age — a promising finding, and sweet vindication for a theory that had initially encountered resistance. When she presented the results of her first experiments to the annual meeting of the American Association of Anatomists in 1965, a man at the back of the room stood up and shouted, “Young lady, that brain cannot change.” She wrote in her autobiographical essay: “It was an uphill battle for women scientists then — even more than now — and people at scientific conferences are often terribly critical. But I felt good about the work, and I simply replied, ‘I’m sorry, sir, but we have the initial experiment and the replication experiment that shows it can.’ ”
News Article | June 23, 2017
Working with colleagues from Harvard Medical School and Würzburg, researchers from Charité -- Universitätsmedizin Berlin have been examining the use of deep brain stimulation in the treatment of Parkison's disease in an attempt to optimize treatment effectiveness. Specifically, they have been looking at which brain regions need to be connected to the electrode used for deep brain stimulation. The researchers found a way to use brain connectivity (i.e. connections in the brain) to predict the best possible relief of Parkinson's Disease symptoms. The results, describing an effective network profile of deep brain stimulation has been reported in the journal Annals of Neurology. Deep brain stimulation (DBS) is an established treatment for Parkinson's disease, usually leading to significant improvement in motor symptoms and quality of life. Symptoms such as movement restrictions, muscle rigidity, or tremor can be alleviated using the neurosurgical procedure which places small electrodes into deep structures of the brain. Whether optimal symptom relief is achieved depends on the correct placement of the electrode. Characteristic connectivity patterns can be observed between the area surrounding the implant and other areas of the brain. "An optimally-positioned neurostimulator disposes of an optimal connectivity profile," explains Dr. Andreas Horn, a researcher at Charité's Department of Neurology and Experimental Neurology. "High treatment effectivity is associated with strong connections between the DBS electrode and specific frontal areas of the brain, such as the 'supplementary motor area'," says Dr. Horn. This relationship was not previously known. The researchers were also able to show that an electrode's connectivity profile can be used to predict the extent to which treatment can alleviate a patient's movement restrictions. They did so by using a special electrode localization procedure which was developed at Charité in the laboratory of Prof. Dr. Andrea Kühn over a period of several years. The procedure continues to be based on exact brain connectivity maps which were developed in cooperation with Harvard Medical School. The researchers used the MRI sequences of more than 1,000 test subjects to create a 'connectivity map' of the average human brain. Using both of these methods in combination, it is possible to produce connectivity profiles for any DBS electrode. Using basic principles from the field of machine learning, the researchers succeeded in producing and validating an optimal connectivity profile. Dr. Andreas Horn and his international research partners successfully ensured the high-precision placement of more than 90 DBS electrodes. The researchers are planning to conduct further studies to develop a patient-specific, 'made-to-measure' method of brain stimulation. This may become feasible since it is possible to analyze a patient's specific connectivity profile using MRI training data even before he or she undergoes DBS electrode placement surgery. "It would be possible to determine the optimal location for stimulation even before the invasive part of the procedure starts," says Dr. Horn. "We are now in the process of developing a complete procedure for connectivity-based deep brain stimulation, which will then need to undergo further validation studies." At some point in the distant future, this will make it possible to run a computer simulation prior to using the treatment in a specific patient.
News Article | June 23, 2017
Working with colleagues from Harvard Medical School and Würzburg, researchers from Charité - Universitätsmedizin Berlin have been examining the use of deep brain stimulation in the treatment of Parkison's disease in an attempt to optimize treatment effectiveness. Specifically, they have been looking at which brain regions need to be connected to the electrode used for deep brain stimulation. The researchers found a way to use brain connectivity (i.e. connections in the brain) to predict the best possible relief of Parkinson's Disease symptoms. The results, describing an effective network profile of deep brain stimulation has been reported in the journal Annals of Neurology*. Deep brain stimulation (DBS) is an established treatment for Parkinson's disease, usually leading to significant improvement in motor symptoms and quality of life. Symptoms such as movement restrictions, muscle rigidity, or tremor can be alleviated using the neurosurgical procedure which places small electrodes into deep structures of the brain. Whether optimal symptom relief is achieved depends on the correct placement of the electrode. Characteristic connectivity patterns can be observed between the area surrounding the implant and other areas of the brain. "An optimally-positioned neurostimulator disposes of an optimal connectivity profile," explains Dr. Andreas Horn, a researcher at Charité's Department of Neurology and Experimental Neurology. "High treatment effectivity is associated with strong connections between the DBS electrode and specific frontal areas of the brain, such as the 'supplementary motor area'," says Dr. Horn. This relationship was not previously known. The researchers were also able to show that an electrode's connectivity profile can be used to predict the extent to which treatment can alleviate a patient's movement restrictions. They did so by using a special electrode localization procedure which was developed at Charité in the laboratory of Prof. Dr. Andrea Kühn over a period of several years. The procedure continues to be based on exact brain connectivity maps which were developed in cooperation with Harvard Medical School. The researchers used the MRI sequences of more than 1,000 test subjects to create a 'connectivity map' of the average human brain. Using both of these methods in combination, it is possible to produce connectivity profiles for any DBS electrode. Using basic principles from the field of machine learning, the researchers succeeded in producing and validating an optimal connectivity profile. Dr. Andreas Horn and his international research partners successfully ensured the high-precision placement of more than 90 DBS electrodes. The researchers are planning to conduct further studies to develop a patient-specific, 'made-to-measure' method of brain stimulation. This may become feasible since it is possible to analyze a patient's specific connectivity profile using MRI training data even before he or she undergoes DBS electrode placement surgery. "It would be possible to determine the optimal location for stimulation even before the invasive part of the procedure starts," says Dr. Horn. "We are now in the process of developing a complete procedure for connectivity-based deep brain stimulation, which will then need to undergo further validation studies." At some point in the distant future, this will make it possible to run a computer simulation prior to using the treatment in a specific patient.
News Article | September 15, 2017
University of Adelaide researchers have confirmed that abnormalities in a common brain chemical are linked to sudden infant death syndrome (SIDS). In the first study of its kind looking at babies outside the United States, researchers from the University of Adelaide's Adelaide Medical School investigated 41 cases of SIDS deaths and discovered striking abnormalities in chemical serotonin within the brain. Serotonin, otherwise known as 5-HT, is a neurotransmitter found in different parts of the human body, including the central nervous system. Among its many roles, serotonin is involved in the regulation of sleep, and also control of the cardiovascular and respiratory systems. This latest research, published in the Journal of Neuropathology & Experimental Neurology, confirms and supports the concept that brainstem dysfunction, resulting in significantly altered serotonin expression, is associated with some SIDS deaths. SIDS is the sudden unexpected death of an infant under one year of age that cannot be explained after a thorough investigation, including an autopsy. It is the leading cause of death in infants between one month and one year of age in Australia and the developed world. The research was conducted by PhD student Fiona Bright under the supervision of University of Adelaide Professor of Pathology Roger Byard. Bright graduated with her PhD from the University of Adelaide on Sept. 14. Her work builds on research conducted in the United States at the Boston Children's Hospital and Harvard Medical School, where Bright was based for 18 months during her combined studies. "Our research is significant because it has confirmed that abnormalities in serotonin in the brain are most definitely linked to cases of SIDS. This helps to support the findings of the American research," Bright says. "Serotonin is a key neurochemical that plays an important role in the control and management of the complex respiratory, cardiovascular and autonomic systems within the human infant brainstem. "Our research suggests that alterations in these neurochemicals may contribute to brainstem dysfunction during a critical postnatal developmental period. As a result, this could lead to an inability of a SIDS infant to appropriately respond to life-threatening events, such as lack of oxygen supply during sleep. "Notably, the SIDS cases we studied were all linked to at least one major risk factor for SIDS, with more than half of the infants found in an adverse sleeping position and having had an illness one month prior to death," Bright says. "Better understanding of the complex role of these neurochemicals, and the exact causes of their dysfunction in the brain, will help future research to develop potential biomarkers for infants at increased risk of SIDS," says Byard. "Ultimately, we hope that this work will lead to improved prevention strategies, helping to save baby's lives and the emotional trauma experienced by many families."
News Article | March 2, 2017
Researchers from the University of Iowa Carver College of Medicine and the University of Miami Miller School of Medicine have shown that a neuroprotective compound tested in rats provides two-pronged protection for brain cells during stroke and improves physical and cognitive outcomes in the treated animals. Every year, nearly 800,000 Americans have a stroke and almost 130,000 die. Survivors often are left with long-term physical and cognitive disability that significantly alters their lives. When a stroke interrupts the brain's blood supply, mature brain cells (neurons) die. In addition, reestablishing blood flow, known as reperfusion, also leads to processes that cause cell death. A part of the brain's natural response to stroke injury is to increase production of new brain cells in two specific regions (the subgranular zone of the hippocampal dentate gyrus and the subventricular zone of the lateral ventricles), which normally make a smaller number of new brain cells every day. Unfortunately, the vast majority of these newborn cells die within one to two weeks, limiting the benefit of this potential repair process. Minimizing the loss of brain cells is a primary goal for new stroke therapies. "If we could prevent the mature brain cells from dying that would be beneficial," says Andrew Pieper, MD, PhD, professor of psychiatry in the UI Carver College of Medicine and co-senior study author. "But if we could also support or enhance this surge in neurogenesis (birth of new neurons), we might be able to further foster recovery, especially in terms of cognitive function, which is critically dependent on the hippocampus." Using rats, Pieper and his colleagues Zachary B. Loris and W. Dalton Dietrich, PhD, tested the effects of a compound called P7C3-A20 on these two aspects of neuroprotection following ischemic stroke. Blood flow to the rats' brains was interrupted for 90 minutes and then the blockage was cleared allowing reperfusion. One group of rats was given the P7C3-A20 compound twice daily for seven days following the stroke. P7C3-A20 has previously been shown to prevent brain cell death in other animal models of neurologic injury, including Parkinson's disease, amyotrophic lateral sclerosis, stress-associated depression, and traumatic brain injury. In terms of the brain itself, the P7C3-A20 compound reduced loss of brain tissue (atrophy) and increased survival of newborn neurons six weeks after stroke. In addition to the improved survival of both mature and newborn neurons, rats that received the P7C3-A20 compound for seven days after stroke also had better physical and cognitive outcomes than untreated rats. Treated rats had improved balance and coordination one week after stroke, and improved learning and memory one month after stroke. The findings were published recently in the journal Experimental Neurology. "There is no previous demonstration of a pharmacologic agent that both protects mature neurons from dying and also boosts the net magnitude of neurogenesis," Pieper says. "Our compound is beneficial in this animal model of stroke, and we're hopeful that it might eventually benefit patients." "Currently there are limited treatments for acute stroke that make a real difference in patient's lives. There is an urgent need to identify, test, and translate new therapies to the clinic," adds Dietrich, co-senior study author and Scientific Director of The Miami Project to Cure Paralysis, professor of neurological surgery, neurology, biomedical engineering and cell biology at the University of Miami where the studies were conducted. "The ability to both protect and repair the injured nervous system has major implications on how we think about improving outcomes in millions of people each year with acute neurological injuries." The neuronal protection provided by the P7C3-A20 compound was also associated with a boost in the levels of a substance called nicotinamide adenine dinucleotide (NAD) in the rats' brains. NAD is emerging as an important player in neuronal health and survival. Levels of this substance are depleted during stroke, and it has been proposed that increasing NAD levels may be a therapeutic target for treating stroke. In this study, P7C3-A20 treatment restored NAD to normal levels in the rats' cortex after a stroke. Importantly, the study examined the effects of P7C3-A20 on cognitive and physical outcomes well beyond the time of the initial stroke. The sustained physical and cognitive improvement seen in the rats up to one month after the stroke suggests that the P7C3-A20 compound provides a long-term benefit. "We found we can give the compound in this critical period immediately after the stroke and it has a lasting effect," notes Pieper, who also is a professor of neurology, radiation oncology, and a psychiatrist with the Iowa City Veterans Affairs Health Care System. In recent years, advances in treatments that break up or remove stroke-causing blood clots have reduced the death rate for stroke and are improving outcomes for patients. The researchers hope that a treatment based on P7C3-A20 used in addition to the clot-clearing therapies might further improve outcomes by protecting brain cells during the traumatic ischemia/reperfusion period. The research was supported by funding from the American Heart Association, The Miami Project to Cure Paralysis, the Mary Alice Smith Fund for Neuropsychiatry Research, the Titan Neurologic Research fund, and the University of Iowa and the Department of Veterans Affairs.
News Article | February 6, 2017
Scientists at the Medical Research Council Brain Network Dynamics Unit at the University of Oxford have pinpointed two distinct mechanisms in the human brain that control the balance between speed and accuracy when making decisions. Their discovery, published in eLife, sheds new light on the networks that determine how quickly we choose an option, and how much information we need to make that choice. A more detailed understanding of this intricate wiring in the brain holds the key to developing better treatments for neurological disorders such as Parkinson's disease. The fundamental trade-off between speed and accuracy in decision making has been studied for more than a century, with a number of studies suggesting that the subthalamic nucleus region of the brain plays a key role. "Previous behavioural studies of decision making do not tell us about the actual events or networks that are responsible for making speed-accuracy adjustments," says senior author Peter Brown, Professor of Experimental Neurology at the University of Oxford. "We wanted to address this by measuring the exact location and timing of electrical activity in the subthalamic nucleus and comparing the results with behavioural data collected while a decision-making task is being performed." Brown and his team first studied the reaction times of 11 patients with Parkinson's disease and 18 healthy participants, who were each asked to perform a moving-dots task. This required them to decide whether a cloud of moving dots appeared to be moving to the left or the right. The difficulty of the task was varied by changing the number of dots moving in one direction, and the participants were given randomly alternating instructions to perform the task with either speed or accuracy. The researchers found that participants made much faster decisions when the task was easier - with the dots moving in a single direction - and when instructed to make a quick decision. They also found, in line with previous studies, that participants made significantly more errors during tests where they spent longer making a decision after being instructed to emphasise accuracy. Using a computational model, they saw that it took longer in the more difficult tests for the brain to accumulate the necessary information to reach a critical threshold and make a decision. When the participants were asked to focus on speed, this threshold was significantly lower than when they focused on accuracy. "The next step was to determine the activated networks in the brain that control these behavioural modifications and the trade-off between fast and accurate decisions," explains first author and postdoctoral fellow Damian Herz. "We measured the electrical activity of groups of nerve cells within the subthalamic nucleus in patients with Parkinson's disease, who had recently been treated with deep brain stimulation. We found two distinct neural networks that differ in the way they are ordered and the way they respond to tasks. "One network increases the amount of information required before executing a decision and is therefore more likely to be activated when accuracy is important, while the second network tends to lower this threshold, especially when the choice needs to be made quickly." The findings add to the increasing evidence that the pre-frontal cortex region of the brain contributes to decision making and opens up further interesting avenues to explore. "We know that changes in activity of one of the sites we identified is also related to movement control," adds Brown. "Close relationships between these neural networks could mean that a common signal is responsible for adjustments in both the speed of decision and of the resulting movement. A better understanding of these mechanisms might make it possible to focus therapeutic interventions on specific neural circuits to improve treatment of neurological disorders in the future."
News Article | January 13, 2017
Traumatic brain injury (TBI) affects more than half a million infants and children in the United States every year. New research shows that specific antibiotics used to inhibit the brain's inflammatory response can help adults, while at the same time negatively affecting children and infants. There are no drugs available to treat TBI, but there are medical treatments used to improve the outcome in people who had suffered serious head injuries. The treatment was found to have a negative effect on the brains which did not complete the development process. The study, published in the journal Experimental Neurology, was conducted by researchers at Drexel University College of Medicine. It showed that when antibiotics were administered to newborn rats in the immediate aftermath of the injury, it aggravated the cognitive impairment. "The developing brain is not the same as the fully mature brain. This study suggests that acute interventions targeting the inflammatory cascade may not be a viable strategy for treating traumatic brain injury in infants and young children," noted Ramesh Raghupathi, PhD, a professor of neurobiology and anatomy in the College of Medicine. What the minocycline drug does is decrease the activation of microglia, the primary immune cells located in the spinal cord and the brain, responsible with protecting the body against foreign pathogens. However, this inhibition of microglia only seems to work in adult brains, while the pediatric model shows a different response, "There was a lot of cell death, damage and inflammation," noted Raghupathi said, lead author of the study. The team tested the drug, treating the newborn rats with minocycline, in one daily dosage over a three-day period. The results showed no improvement in the brain activity. Further, the researchers extended the period to nine days instead of just three, and the baby rats showed significant memory issues as well as complementary behavioral problems. The researchers attributed this result to the role microglia plays in brain development, cleaning the brain of debris and dead neurons as to make room for the functional neurons left to work under normal conditions. By inhibiting this function inside the brains of newborns, the normal process of brain maturation is negatively affected, and cognitive functions can suffer long-term impairment. "Whereas injury-induced spatial learning deficits remained unaffected by minocycline treatment, memory deficits appeared to be significantly worse. Sex had minimal effects on either injury-induced alterations or the efficacy of minocycline treatment. Collectively, these data demonstrate the differential effects of minocycline in the immature brain following impact trauma and suggest that minocycline may not be an effective therapeutic strategy for TBI in the immature brain," noted the research. In the following researches, the scientists will administer the treatment after three or four weeks, as opposed to the 11-days old rats used in the current research, to evaluate the effects. More time for the brain development process could make the difference between a positive and a negative outcome of the treatment, according to the researchers, who wish to establish the age from when on the treatment doesn't cause further cognitive and behavioral impairment, with as much precision as possible. © 2017 Tech Times, All rights reserved. Do not reproduce without permission.