Chapter 5. The Sensorimotor System

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By Benedict Carey Soldiers with deep wounds sometimes feel no pain at all for hours, while people without any detectable injury live in chronic physical anguish. How to explain that? Over drinks in a Boston-area bar, Ronald Melzack, a psychologist, and Dr. Patrick Wall, a physiologist, sketched out a diagram on a cocktail napkin that might help explain this and other puzzles of pain perception. The result, once their idea was fully formed, was an electrifying theory that would become the founding document for the field of modern pain studies and establish the career of Dr. Melzack, whose subsequent work deepened medicine’s understanding of pain and how it is best measured and treated. Dr. Melzack died on Dec. 22 in a hospital near his home in Montreal, where he lived, his daughter, Lauren Melzack, said. He was 90, and had spent most of his professional life as a professor of psychology at McGill University. When Dr. Melzack and Dr. Wall, then at the Massachusetts Institute of Technology, met that day in 1959 or 1960 (accounts of their encounter vary), pain perception was thought to work something like a voltmeter, in which nerves send signals up to the brain that reflect the severity of the injury. But that model failed to explain not only battlefield experience but also a host of clinical findings and everyday salves. Most notably, rubbing a wound lessens its sting — and accounting for just that common sensation proved central to the new theory. Doctors knew that massaging the skin activated so-called large nerve fibers, which are specialized to detect subtle variations of touch; and that deeper, small fibers sounded the alarm of tissue damage. The two researchers reasoned that all these sensations must pass through a “gate” in the spinal cord, which adds up their combined signals before sending a message to the brain. In effect, activating the large fibers blocks signals from the smaller ones, by closing the gate. © 2020 The New York Times Company

Keyword: Pain & Touch
Link ID: 26950 - Posted: 01.13.2020

Amber Dance The girl tried hard to hold her arms and hands steady, but her fingers wriggled and writhed. If she closed her eyes, the squirming got worse. It wasn’t that she lacked the strength to keep her limbs still — she just didn’t seem to have control over them. Carsten Bönnemann remembers examining the teenager at a hospital in Calgary, Canada, in 2013. As a paediatric neurologist with the US National Institute of Neurological Disorders and Stroke in Bethesda, Maryland, he often travelled to weigh in on puzzling cases. But he had never seen anything like this. If she wasn’t looking at her limbs, the girl didn’t seem to have any clue where they were. She lacked the sense of her body’s position in space, a crucial ability known as proprioception. “This is something that just doesn’t occur,” says Bönnemann. His team sequenced the girl’s genes, and those of another girl with similar symptoms1, and found mutations in a gene called PIEZO2. Their timing was fortunate: just a few years earlier, researchers looking for the mechanisms that cells use to sense touch had found that the gene encoded a pressure-sensitive protein2. The discovery of Piezo2 and a related protein, Piezo1, was a high point in a decades-long search for the mechanisms that control the sense of touch. The Piezos are ion channels — gates in the cell membrane that allow ions to pass through — that are sensitive to tension. “We’ve learned a lot about how cells communicate, and it’s almost always been about chemical signalling,” says Ardem Patapoutian, a molecular neurobiologist at Scripps Research in La Jolla, California, whose group identified the Piezos. “What we’re realizing now is that mechanical sensation, this physical force, is also a signalling mechanism, and very little is known about it.” © 2020 Springer Nature Limited

Keyword: Pain & Touch
Link ID: 26944 - Posted: 01.09.2020

By Jane E. Brody If you live with or work with someone who suffers from migraine, there’s something very important you should know: A migraine is not “just a headache,” as many seem to think. Nor is it something most sufferers can simply ignore and get on with their lives. And if you are a migraine sufferer, there’s something potentially life-changing that you should know: There are now a number of medications available that can either prevent or alleviate many attacks, as well as a newly marketed wearable nerve-stimulating device that can be activated by a smartphone to relieve the pain of migraine. Migraine is a neurological disorder characterized by recurrent attacks of severe, often incapacitating headache and dysfunction of the autonomic nervous system, which controls the body’s myriad automatic activities like digestion and breathing. The throbbing or pulsating pain of migraine is often accompanied by nausea and vomiting. Translation: Migraine is a headache, all right, but with body-wide effects because the brain converses with the rest of the body. It is often severe enough to exact a devastating toll on someone’s ability to work, interact with others, perform the tasks of daily life, or even be in a normal living environment. When in the throes of a migraine attack, sufferers may be unable to tolerate light, noise, smells or even touch. Dr. Stephen Silberstein, a neurologist at Thomas Jefferson University and director of the Jefferson Headache Center, told me “There are 47 million people in this country with migraine, and for six million, the condition is chronic, which means they have more than 15 headache days a month,” he said. “It’s time to destigmatize migraine and provide sufferers with effective treatment,” said Dr. David W. Dodick, neurologist at the Mayo Clinic in Scottsdale. “They’re not fakers, weak individuals who are trying to get out of work.” © 2020 The New York Times Company

Keyword: Pain & Touch
Link ID: 26936 - Posted: 01.07.2020

By Sharon Jayson AUSTIN, Texas — Retired state employees Vickey Benford, 63, and Joan Caldwell, 61, are Golden Rollers, a group of the over-50 set that gets out on assorted bikes — including trikes for adults they call “three wheels of awesome” — for an hour of trail riding and camaraderie. “I love to exercise, and I like to stay fit,” said Caldwell, who tried out a recumbent bike, a low-impact option that can be easier on the back. “It keeps me young.” Benford encouraged Caldwell to join the organized rides, which have attracted more than 225 riders at city rec centers and senior activity centers. The cyclists can choose from a small, donated fleet of recumbent bikes, tandem recumbents and tricycles. “With seniors, it’s less about transportation and more about access to the outdoors, social engagement and quality of life,” said Christopher Stanton, whose idea for Golden Rollers grew out of the Ghisallo Cycling Initiative, a youth biking nonprofit he founded in 2011. But that’s not all, according to brain scientists. They point to another important benefit: Exercising both body and brain can help people stay healthier longer. The new thinking about aging considers not just how long one lives, but how vibrant one stays later in life. “If you’re living, you want to be living well,” said Tim Peterson, an assistant professor of internal medicine at the Washington University School of Medicine in St. Louis. “Most people who were interested in life span and were studying genes — which control life span — switched to ‘healthspan.’” “Healthspan,” a coinage now gaining traction, refers to the years that a person can expect to live in generally good health — free of chronic illnesses and cognitive decline that can emerge near life’s end. Although there’s only so much a person can do to delay the onset of disease, there’s plenty that scientists are learning to improve your chances of a better healthspan. © 2020 Kaiser Family Foundation

Keyword: Development of the Brain
Link ID: 26932 - Posted: 01.04.2020

By Gretchen Reynolds What’s good for your muscles can also be good for your mind. A Single Workout Can Alter the Brain A single, moderate workout may immediately change how our brains function and how well we recognize common names and similar information, according to a promising new study of exercise, memory and aging. The study adds to growing evidence that exercise can have rapid effects on brain function and also that these effects could accumulate and lead to long-term improvements in how our brains operate and we remember. Until recently, scientists thought that by adulthood, human brains were relatively fixed in their structure and function, especially compared to malleable tissues, like muscle, that continually grow and shrivel in direct response to how we live our lives. But multiple, newer experiments have shown that adult brains, in fact, can be quite plastic, rewiring and reshaping themselves in various ways, depending on our lifestyles. A hormone that is released during exercise may improve brain health and lessen the damage and memory loss that occur during dementia, a new study finds. The study, which was published this month in Nature Medicine, involved mice, but its findings could help to explain how, at a molecular level, exercise protects our brains and possibly preserves memory and thinking skills, even in people whose pasts are fading. Considerable scientific evidence already demonstrates that exercise remodels brains and affects thinking. Researchers have shown in rats and mice that running ramps up the creation of new brain cells in the hippocampus, a portion of the brain devoted to memory formation and storage. Exercise also can improve the health and function of the synapses between neurons there, allowing brain cells to better communicate. © 2019 The New York Times Company

Keyword: Alzheimers
Link ID: 26925 - Posted: 12.30.2019

By Debbie Jackson BBC Scotland "Fluffing your son's hair, really hugging him, holding his hand." For someone who has been through what she has in the space of a year, Corinne Hutton doesn't need much to make her happy. Last January she got the double hand transplant she had been waiting more than five years for, and feared would never happen. This January, she will celebrate her "handiversary", a year since a surgeon handed her back her independence. Being able to do the simplest things for 11-year-old son Rory means the world to Finding Your Feet charity founder Cor. "From an emotional point of view to be able to do things for him - make the packed lunches or the washing, or do the ironing is great," she said. "But on top of that, being able to hold his hand, fluff his hair, little things that might not be hugely exciting to him - but they matter a lot to me. "People don't appreciate what it means to have lost them," she said. Cor became the first Scot to undergo a double hand transplant when, in a 12-hour procedure, Prof Simon Kay attached two donor hands to her arms at Leeds general Infirmary. The 48-year-old lost her hands and feet in 2013 after suffering acute pneumonia and sepsis, which almost killed her. After more than a dozen false alarms over the years, a match for her own blood group, skin tone and hand size had been found. Much celebration and wonder was made of the news that the transplant had finally happened, but the aftermath was far from easy. © 2019 BBC.

Keyword: Pain & Touch
Link ID: 26922 - Posted: 12.30.2019

By Eva Frederick One day in 2014, primatologist Yuko Hattori was trying to teach a mother chimpanzee in her lab to keep a beat. Hattori would play a repetitive piano note, and the chimp would attempt to tap out the rhythm on a small electronic keyboard in hopes of receiving a tasty piece of apple. Everything went as expected in the experiment room, but in the next room over, something strange was happening. Another chimpanzee, the mother’s son, heard the beat and began to sway his body back and forth, almost as if he were dancing. “I was shocked,” Hattori says. “I was not aware that without any training or reward, a chimpanzee would spontaneously engage with the sound.” Hattori has now published her research showing that chimps respond to sounds, both rhythmic and random, by “dancing.” “This study is very thought-provoking,” says Andrea Ravignani, a cognitive biologist at the Seal Rehabilitation and Research Centre who researches the evolution of rhythm, speech, and music. The work, she says, could shed light on the evolution of dancing in humans. For their the study, Hattori and her colleague Masaki Tomonaga at Kyoto University played 2-minute clips of evenly spaced, repetitive piano tones (heard in the video above) to seven chimpanzees (three males and four females). On hearing the sound, the chimps started to groove, swaying back and forth and sometimes tapping their fingers or their feet to the beat or making howling “singing” sounds, the researchers report today in the Proceedings of the National Academy of Sciences. All of the chimps showed at least a little bit of rhythmic movement, though the males spent much more time moving to the music than females. © 2019 American Association for the Advancement of Science.

Keyword: Evolution; Hearing
Link ID: 26916 - Posted: 12.26.2019

By Richard Sima Luke Miller, a cognitive neuroscientist, was toying with a curtain rod in his apartment when he was struck by a strange realization. When he hit an object with the rod, even without looking, he could tell where it was making contact like it was a sensory extension of his body. “That’s kind of weird,” Miller recalls thinking to himself. “So I went [to the lab], and we played around with it in the lab.” Sensing touch through tools is not a new concept, though it has not been extensively investigated. In the 17th century, philosopher René Descartes discussed the ability of blind people to sense their surroundings through their walking cane. While scientists have researched tool use extensively, they typically focused on how people move the tools. “They, for the most part, neglected the sensory aspect of tool use,” Miller says. In a 2018 Nature study, Miller and his colleagues at Claude Bernard Lyon 1 University in France reported that humans are actually quite good at pinpointing where an object comes into contact with a handheld tool using touch alone, as if the object were touching their own skin. A tool is not innervated like our skin, so how does our brain know when and where it is touched? Results in a follow-up study, published in December in Current Biology, reveal that the brain regions involved with sensing touch on the body similarly processes it on the tool. “The tool is being treated like a sensory extension of your body,” Miller says. In the initial experiment, the researchers asked 16 right-handed subjects to determine where they felt touches on a one-meter-long wooden rod. In a total of 400 trials, each subject compared the locations of two touches made on the rod: If they were felt in different locations, participants did not respond. If they were in the same location, the people in the study tapped a foot pedal to indicate whether the touches were close or far from their hand. Even without any experience with the rod or feedback on their performance, the participants were, on average, 96 percent accurate. © 2019 Scientific American,

Keyword: Pain & Touch
Link ID: 26914 - Posted: 12.26.2019

Scientists say they have discovered a possible underlying cause of the neurological disorder, motor neurone disease (MND). The University of Exeter team says it has found evidence that MND is linked to an imbalance of cholesterol and other fats in cells. It says the research could lead to more accurate diagnosis and new treatments. MND affects around 5,000 people in the UK and causes more than 2,000 deaths a year. What is MND? Motor neurone disease is a group of diseases that affect the nerve cells in the brain and spinal cord that tell your muscles what to do. Also known as ALS, it causes muscle weakness and stiffness. Eventually people with the disease are unable to move, talk, swallow and finally, breathe. There is no cure and the exact causes are unclear - it's been variously linked to genes, exposure to heavy metals and agricultural pollution. What did the researchers find? Scientists at the University of Exeter say they had a "eureka moment" when they realised that 13 genes - which, if altered, can cause the condition - were directly involved in processing cholesterol. They say their theory could help predict the course and severity of the disease in patients and monitor the effect of potential new drugs. The theory is outlined in a paper, published in Brain: A Journal of Neurology. Lead author Prof Andrew Crosby said: "For years, we have known that a large number of genes are involved in motor neurone disease, but so far it hasn't been clear if there's a common underlying pathway that connects them." The finding particularly relates to what is known as the "spastic paraplegias", where the malfunction is in the upper part of the spinal cord. Dr Emma Baple, also from the University of Exeter Medical School, said: "Currently, there are no treatments available that can reverse or prevent progression of this group of disorders. Patients who are at high risk of motor neurone disease really want to know how their disease may progress and the age at which symptoms may develop, but that's very difficult to predict." © 2019 BBC

Keyword: ALS-Lou Gehrig's Disease
Link ID: 26902 - Posted: 12.18.2019

By Gretchen Reynolds Top athletes’ brains are not as noisy as yours and mine, according to a fascinating new study of elite competitors and how they process sound. The study finds that the brains of fit, young athletes dial down extraneous noise and attend to important sounds better than those of other young people, suggesting that playing sports may change brains in ways that alter how well people sense and respond to the world around them. For most of us with normal hearing, of course, listening to and processing sounds are such automatic mental activities that we take them for granted. But “making sense of sound is actually one of the most complex jobs we ask of our brains,” says Nina Kraus, a professor and director of the Auditory Neuroscience Laboratory at Northwestern University in Evanston, Ill., who oversaw the new study. Sound processing also can be a reflection of broader brain health, she says, since it involves so many interconnected areas of the brain that must coordinate to decide whether any given sound is familiar, what it means, if the body should respond and how a particular sound fits into the broader orchestration of other noises that constantly bombard us. For some time, Dr. Kraus and her collaborators have been studying whether some people’s brains perform this intricate task more effectively than others. By attaching electrodes to people’s scalps and then playing a simple sound, usually the spoken syllable “da,” at irregular intervals, they have measured and graphed electrical brain wave activity in people’s sound-processing centers. © 2019 The New York Times Company

Keyword: Attention
Link ID: 26901 - Posted: 12.18.2019

By Tina Hesman Saey WASHINGTON — Clumps of misfolded proteins cause traffic jams in brain cells. Those jams may have deadly consequences in neurodegenerative diseases. Clusters of prions block passage of crucial cargo along intracellular roadways in brain cells, cell biologist Tai Chaiamarit of the Scripps Research Institute in La Jolla, Calif., reported December 10 at the joint annual meeting of the American Society for Cell Biology and the European Molecular Biology Organization. Prions, misshaped versions of a normal brain protein, clump together in large aggregates that are hallmarks of degenerative brain diseases, such as mad cow disease in cattle, chronic wasting disease in deer and Creutzfeldt-Jakob disease in people. It’s unclear why those clumpy proteins are so deadly to nerve cells called neurons, but the new study may provide clues about what goes wrong in these diseases. Axons, the long stringlike projections of nerve cells that carry electrical signals to other nerves, are the sites of prion traffic jams, Chaiamarit and colleagues found. As more prions clump together, they cause swollen bulges that make the axon look like a snake that has just swallowed a big meal. Through a microscope, Chaiamarit and colleagues saw mitochondria being transported toward the cell’s furthest reaches derailed at the bulges. Mitochondria, cells’ energy-generating organelles, are carried outbound from the main body of the cell by a motor protein called kinesin-1. The protein motors along molecular rails called microtubules. A different motor protein, dynein, transports mitochondria back toward the cell body along those same rails. © Society for Science & the Public 2000–2019

Keyword: Prions
Link ID: 26895 - Posted: 12.13.2019

By Sharon Begley, STAT Even allowing for the fact that these were lilliputian brains, they were not behaving at all according to plan. From the first days of the tiny lab-grown organs’ development, primitive “progenitor cells” romped out of their birthplaces in the deep interior and quickly turned into neurons and glia, specialized cells that do the brain’s heavy lifting, from thinking and feeling and moving to boring old neurological housekeeping. But the cells were jumping the gun. In healthy developing human brains, progenitor cells spend a good chunk of prenatal existence simply reproducing, vastly increasing their numbers and postponing becoming other brain cells. The impatient progenitor cells, however, were in cerebral organoids—minuscule 3-D versions of the brain—created from the cells of people with Huntington’s disease in hopes of mimicking the patients’ actual brain development decades earlier. It was new evidence that, in their understanding of this devastating genetic illness, scientists know only half the story: In addition to being a neurodegenerative disease, it is also neurodevelopmental, starting in the womb. These recent findings and other research are spurring a radical rethinking of Huntington’s, with implications for the age when any potential cure is likely to be most effective. “It’s not conclusive, but there is suggestive evidence that neurodevelopment is altered in Huntington’s disease,” said neurobiologist Mahmoud Pouladi of the National University of Singapore, who led the organoid work. If so, then if scientists discover a way to repair the mutant gene or remove the aberrant molecules it makes, “the earlier you intervene the better it should be.” In contrast, today’s most-watched clinical trials in Huntington’s include only adults, often middle-aged ones, reflecting the belief that most mutation carriers can reach their 30s or beyond cerebrally unscathed. In fact, doctors and advocacy groups strongly discourage genetic testing for Huntington’s in anyone under 18, presuming there’s nothing to be gained. According to the genetic-testing guidelines from the Huntington’s Disease Society of America, “Predictive testing of minors currently has no medical benefits and the possibility for psychosocial harm and lowered self-esteem is high.” © 2019 Scientific American

Keyword: Huntingtons
Link ID: 26889 - Posted: 12.11.2019

By Jonah Engel Bromwich Pete Frates, a former college baseball player whose participation in the social media phenomenon known as the Ice Bucket Challenge helped raise more than $100 million toward fighting amyotrophic lateral sclerosis, commonly known as A.L.S. or Lou Gehrig’s disease, died on Monday at his home in Beverly, Mass. He was 34. His death was announced in a statement by Boston College, his alma mater. Quoting his family, it said he died “after a heroic battle with A.L.S.” Mr. Frates learned he had the disease in 2012. A.L.S. attacks the body’s nerve cells and leads to full paralysis. Patients are typically expected to live for two to five years from the time of diagnosis. Mr. Frates did not create the Ice Bucket Challenge, in which participants dumped buckets of ice water over their heads while pledging to donate money to fight A.L.S. But a Facebook video in July 2014 showing him doing his version of the challenge — in which he bobbed his head to Vanilla Ice’s song “Ice Ice Baby” — prompted a surge in participation that summer, to where it became a viral sensation. LeBron James, Bill Gates, Oprah Winfrey and other celebrities stepped forward to be drenched, and millions of others followed suit. Mr. Frates became one of the most visible supporters of the effort, and in August 2014 he completed the challenge again (this time with ice water) at Fenway Park, along with members of the Boston Red Sox organization. The videos were inescapable for anyone on Facebook, and the A.L.S. Association, a Washington-based nonprofit that works to fight the disease, received more than $115 million. In 2015 the organization released an infographic showing how those funds were being spent. About $77 million, or 67 percent, of the money was used for research that ultimately identified the NEK1 gene, which contributes to the disease. The finding gave scientists guidance in developing treatment drugs. © 2019 The New York Times Company

Keyword: ALS-Lou Gehrig's Disease
Link ID: 26885 - Posted: 12.10.2019

By Austin Frakt Some days I’m grumpy; other times, my head hurts or my feet or my arms do. Yet when I play the trumpet, my mood improves and the pain disappears. Why? Alternative medicine — including music therapy — is full of pain-relief claims. Although some are simply too good to be true, the oddities of pain can explain why others hold up, as well as why my trumpet playing helps. One thing we tend to believe about pain, but is wrong, is that it always stems from a single, fixable source. Another is that pain is communicated from that source to our brains by “pain nerves.” That’s so wrong it’s called “the naïve view” by neuroscientists. In truth, pain is in our brain. Or as the author and University of California, San Diego, neuroscientist V. S. Ramachandran put it, “Pain is an opinion.” We feel it because of how our brain interprets input transmitted to it from all our senses, not necessarily because of the inherent properties of the input itself. There are no nerves dedicated to sensing and transmitting pain. Anyone who has willed themselves to not feel a tickle as ticklish can appreciate the difference between stimulation and our perception of it. Pain can be experienced and relieved in phantom limbs. Discomfort and swelling increase when people believe a painful hand or knee is larger. They decrease when it seems smaller, for example in a distorted image or based on virtual reality technology. Injections are less painful when we don’t watch them. Using our brains, we can exert some control over it. © 2019 The New York Times Company

Keyword: Pain & Touch; Emotions
Link ID: 26865 - Posted: 12.02.2019

By Denise Grady A lifelong swimmer leapt into deep water near his lakeside home, and was horrified to find himself completely unable to swim. Had his wife not rescued him, he might have drowned. He had recently received an electronic brain implant to control tremors and other symptoms of Parkinson’s disease, and somehow the signals from the device had knocked out his ability to coordinate his arms and legs for swimming. He was one of nine patients, all good swimmers despite having Parkinson’s, who had the same strange, dangerous side effect from deep brain stimulators. Three of them tried turning off the stimulators, and immediately could swim again, according to an article in the journal Neurology by a medical team from the University of Zurich. At first, doctors thought the case of the man in the lake was an isolated event, Dr. Christian R. Baumann, an author of the paper, said in an interview. But when the same thing happened to another patient, one who had been a competitive swimmer, Dr. Baumann and his colleagues began to ask other patients about swimming. They found seven more cases among about 250 patients. About 150,000 people worldwide have brain implants made by Medtronic, the leading manufacturer, the company said. Most had the implants for relief of Parkinson’s symptoms. The swimming problem is not that common Dr. Baumann said, adding: “I think it’s a minority of patients. We find many who are still wonderfully able to swim and we don’t know why. We have no clue. They are treated in the same region of the brain. But this is life-threatening, and we need to pay more attention in the future.” Now, Dr. Baumann warns all patients with stimulators never to go into deep water alone. © 2019 The New York Times Company

Keyword: Parkinsons
Link ID: 26860 - Posted: 11.29.2019

Ruth Williams Throughout the animal kingdom, there are numerous examples of neurons that respond to multiple stimuli and faithfully transmit information about those various inputs. In the mouse, for example, there are certain neurons that respond to both temperature and potentially damaging touch. In the fruit fly, there are neurons that sense light, temperature, pain, and proprioceptive stimuli—those arising as a result of body position and movement. And in C. elegans, two sensory neurons, known as PVD neurons, that run the length of the body on either side are thought to regulate proprioception as well as responses to harsh touch and cold temperature. Scientists have now figured out how a single PVD neuron can relay two different stimuli: while harsh touch results in typical firing of the neuron—an impulse that travels the length of the cell—proprioception causes a localized response in one part of the cell with no apparent involvement of the rest. The findings are reported today (November 14) in Developmental Cell. “[The] paper illustrates that different parts of the neuron do different things,” says neuroscientist Scott Emmons of Albert Einstein College of Medicine who did not participate in the research, “and that just makes the whole system much more complex to interpret,” he says. To examine how a single neuron interprets distinct inputs and drives corresponding behaviors, neuroscientist Kang Shen of Stanford University and colleagues focused on PVD neuron–regulated escape behavior when a worm is poked with a wire and the worm’s normal wiggling motion as it responds to proprioceptive stimuli. © 1986–2019 The Scientist

Keyword: Pain & Touch; Development of the Brain
Link ID: 26823 - Posted: 11.16.2019

Catherine Offord A clinical trial of a gene therapy for Duchenne muscular dystrophy has been halted after a patient suffered serious side effects following treatment, Reuters reports today (November 12). After receiving Solid Biosciences’s experimental therapy, SGT-001, the patient experienced kidney injury and drops in red blood cell count, leading the US Food and Drug Administration (FDA) to place the study on hold. “We are encouraged that this patient is recovering,” Ilan Ganot, Solid Biosciences’s CEO, president, and cofounder, says in a statement. “In the coming weeks, we anticipate that we will have a better understanding of the biological activity and potential benefit of SGT-001. We look forward to sharing this additional data and working with the FDA to resolve the clinical hold and determining next steps for the program.” SGT-001 has been administered to six people so far, and involves the transfer of an engineered version of the dystrophin gene DMD, which is dysfunctional in people with Duchenne muscular dystrophy, using an adeno-associated virus (AAV) as a vector. Sarepta Therapeutics, Pfizer, and other biopharmaceutical companies are investigating similar approaches to treat the condition, although the choice of AAV varies. See “Positive Trial Results for Experimental DMD Gene Therapy” This isn’t the first time Solid Biosciences’s trial of SGT-001 has been put on hold. Early last year, the FDA halted the same study after a patient receiving a low dose of the therapy experienced a drop in red blood cell count and had to be hospitalized. The company was allowed to resume the trial last June after making changes to the study design. © 1986–2019 The Scientist

Keyword: Movement Disorders; Muscles
Link ID: 26816 - Posted: 11.14.2019

Nicole Ireland · Recent video from Thailand showing paralyzed Humboldt Broncos hockey player Ryan Straschnitzki moving his legs after an electrical stimulation device was surgically implanted in his spine has sparked excitement — as well as questions — about therapies available to Canadians with spinal injuries. The procedure Straschnitzki, 20, had is called epidural stimulation, and although promising, it's still highly experimental, experts in both Canada and the U.S. say. It's in early stages of clinical trials in the U.S. and Europe to evaluate the safety and effectiveness of restoring physical abilities — from bowel and bladder function to moving arms and legs — to people who desperately want to get some normalcy back after spinal injury. Barry Munro understands all too well why people's immediate reaction is to ask why they can't try the procedure here in Canada. He's been hoping for — and working toward — finding a cure for spinal cord injury ever since he dove into a lake in his 20s and was left quadriplegic. Now 55, Munro is chief development officer for the Canadian Spinal Research Organization and works with the North American Spinal Injury Consortium. For more than 30 years, he's seen the headlines come and go, inciting hope that a cure is on the horizon. "I've been down this road before," Munro told CBC News. "I really, really believe in finding a cure and believe it will happen and I have that hope. But — there's a big but — we have to be careful." Milos Popovich, director of the KITE Research Institute at the University Health Network's Toronto Rehabilitation Institute, echoes that need to proceed with caution. He said that epidural stimulation must proceed through many more stages of scientifically sound clinical trials to prove it works before it could be made available as a therapy in Canada. ©2019 CBC/Radio-Canada.

Keyword: Regeneration; Movement Disorders
Link ID: 26810 - Posted: 11.11.2019

By Tina Hesman Saey A newly discovered type of mitochondrial self-destruction may make some brain cells vulnerable to ALS, also known as Lou Gehrig’s disease. In mice genetically engineered to develop some forms of a degenerative nerve disease similar to amyotrophic lateral sclerosis, energy-generating organelles called mitochondria appear to dismantle themselves without help from usual cell demolition crews. This type of power plant self-destruction was spotted in upper motor neurons, brain nerve cells that help initiate and control movements, but not in neighboring cells, researchers report November 7 in Frontiers in Cellular Neuroscience. Death of those upper motor neurons is a hallmark of ALS, and the self-destructing mitochondria may be an early step that sets those cells up to die later. Pembe Hande Özdinler, a cellular neuroscientist at Northwestern University Feinberg School of Medicine in Chicago, and her colleagues have dubbed the mitochondrial dissolution “mitoautophagy.” It is a distinct process from mitophagy, the usual way that cellular structures called autophagosomes and lysosomes remove damaged mitochondria from the cell, Özdinler says. Usually, clearing out old or damaged mitochondria is important for cells to stay healthy. When mitochondria sustain too much damage, they may trigger the programmed death of the entire cell, known as apoptosis (SN: 8/9/18). Özdinler’s team spotted what she describes as “awkward” mitochondria in electron microscope images of upper motor neurons from 15-day-old mice. These unweaned mice are equivalent to human teenagers, Özdinler says. ALS typically doesn’t strike until people are 40 to 70 years old. But by the time symptoms appear, motor neurons are already damaged, so Özdinler’s group looked at the young mice to capture the earliest signs of the disease. © Society for Science & the Public 2000–2019

Keyword: ALS-Lou Gehrig's Disease
Link ID: 26804 - Posted: 11.08.2019

Maheen Mausoof Adamson, Ph.D. The 1982 science fiction film classic Blade Runner is a gritty detective story set in the dystopian future that raises questions about what it means to be human. In the film, Harrison Ford plays Rick Deckard, a police officer turned bounty hunter searching the streets of Los Angeles for a replicant (human-like androids) rebellion leader Roy Batty. Batty is presented as a technologically perfected being fitted with a human-template brain completely rewired to create an enemy to be deathly feared. Fear of the perfect altered brain is prominent in science fiction—and may be particularly prevalent today, amid growing concerns about genetic editing and artificial intelligence. The prospect of a fully artificial human brain remains very distant. However, we are in the midst of a neuromodulation revolution that will increase our ability to treat disease and optimize human performance. We must, however, carefully consider the benefits and risks of these techniques in fully evaluating their potential for society as well as the individual. A large number of patients suffering from neurological or psychiatric disorders—depression, pain, and post-traumatic stress disorder among them—are resistant to or can develop resistance to standard medication and psychotherapy, suggesting the need for new approaches. Neuromodulation may possibly be such an approach. The term (aka neurostimulation) refers to direct stimulation and modification of the nervous system through the use of electrical, chemical, or mechanical signals. Neuromodulation therapy is already used to treat many brain disorders, most commonly movement disorders, chronic pain, and depression. © 2019 The Dana Foundation.

Keyword: Parkinsons; Depression
Link ID: 26797 - Posted: 11.07.2019