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Experimental implant shows promise for restoring voluntary movement after spinal cord injury

UCLA scientists test electrical stimulation that bypasses injury; technique boosts patient’s finger control, grip strength up to 300 percent Elaine Schmidt | December 13, 2016 Aspinal stimulator being tested by doctors at Ronald Reagan UCLA Medical Center is showing promise in restoring hand strength and movement to a California man who broke his neck in a dirt bike accident five years ago. In June, Brian Gomez, now 28, became one of the first people in the world to undergo surgery for the experimental device. UCLA scientists inserted the 32-electrode stimulator below the site of Gomez’s spinal cord injury, near the C-5 vertebrae in the middle of his neck. That’s the area most commonly associated with quadriplegia, the loss of function and feeling in all four limbs. “The spinal cord contains alternate pathways that it can use to bypass the injury and get messages from the brain to the limbs,” said Dr. Daniel Lu, an associate professor of neurosurgery at the David Geffen School of Medicine at UCLA and director of the school’s Neuroplasticity and Repair Laboratory. “Electrical stimulation trains the spinal cord to find and use these pathways.” Although other devices have shown promise recently for treating paralysis, they were either tested in animals or relied on robotic limbs. The approach used by the UCLA doctors is unique because it is designed to boost patients’ abilities to move their own hands, and because the device is implanted in the spine instead of the brain. The technique essentially gets the nerve signal to behave like a driver who avoids rush-hour traffic by taking side streets instead of a busy highway. “If there is an accident on the freeway, traffic comes to a standstill, but there are [...]

Regenerative Medicine: New Clue from Fish about Healing Spinal Cord Injuries

Posted on November 15, 2016 by Dr. Francis Collins Caption: Tissue section of zebrafish spinal cord regenerating after injury. Glial cells (red) cross the gap between the severed ends first. Neuronal cells (green) soon follow. Cell nuclei are stained blue and purple. Credit: Mayssa Mokalled and Kenneth Poss, Duke University, Durham, NC Certain organisms have remarkable abilities to achieve self-healing, and a fascinating example is the zebrafish (Danio rerio), a species of tropical freshwater fish that’s an increasingly popular model organism for biological research. When the fish’s spinal cord is severed, something remarkable happens that doesn’t occur in humans: supportive cells in the nervous system bridge the gap, allowing new nerve tissue to restore the spinal cord to full function within weeks. Pretty incredible, but how does this occur? NIH-funded researchers have just found an important clue. They’ve discovered that the zebrafish’s damaged cells secrete a molecule known as connective tissue growth factor a (CTGFa) that is essential in regenerating its severed spinal cord. What’s particularly encouraging to those looking for ways to help the 12,000 Americans who suffer spinal cord injuries each year is that humans also produce a form of CTGF. In fact, the researchers found that applying human CTGF near the injured site even accelerated the regenerative process in zebrafish. While this growth factor by itself is unlikely to produce significant spinal cord regeneration in human patients, the findings do offer a promising lead for researchers pursuing the next generation of regenerative therapies. As reported in the journal Science, researchers led by Kenneth Poss and postdoctoral fellow Mayssa Mokalled of Duke University, Durham, NC, made this discovery by screening for genes that switch on soon after spinal cord injury. Their search produced [...]

Researchers amplify regeneration of spinal nerve cells

DALLAS – Oct. 11, 2016 – UT Southwestern Medical Center researchers successfully boosted the regeneration of mature nerve cells in the spinal cords of adult mammals – an achievement that could one day translate into improved therapies for patients with spinal cord injuries. “This research lays the groundwork for regenerative medicine for spinal cord injuries. We have uncovered critical molecular and cellular checkpoints in a pathway involved in the regeneration process that may be manipulated to boost nerve cell regeneration after a spinal injury,” said senior author Dr. Chun-Li Zhang, Associate Professor of Molecular Biology at UT Southwestern. Dr. Zhang cautioned that this research in mice, published today by Cell Reports, is still in the early experimental stage and is not ready for clinical translation. “Spinal cord injuries can be fatal or cause severe disability. Many survivors experience paralysis, reduced quality of life, and enormous financial and emotional burdens,” said lead author Dr. Lei-Lei Wang, a postdoctoral researcher in Dr. Zhang’s lab whose series of in vivo (in a living animal) screens led to the findings. Spinal cord injuries can lead to irreversible neural network damage that, combined with scarring, can ultimately impair motor and sensory functions. These outcomes arise because adult spinal cords have very limited ability to regenerate damaged neurons to aid in healing, said Dr. Zhang, a W.W. Caruth, Jr. Scholar in Biomedical Research and member of the Hamon Center for Regenerative Science and Medicine. Dr. Zhang’s lab focuses on glial cells, the most abundant non-neuronal type of cells in the central nervous system. Glial cells support nerve cells in the spinal cord and form scar tissue in response to injury. In 2013 and 2014, the Zhang laboratory created new nerve cells in the brains [...]

Stem Cell Agency Spinal Cord Injury Clinical Trial Passes Safety Hurdles

Posted: August 31, 2016 Oakland, CA – A clinical trial using stem cells to treat people with recent spinal cord injuries has cleared two key safety hurdles, and been given approval to expand the therapy to a larger group of patients with a much higher dose of cells. Asterias Biotherapeutics announced that its Data Monitoring Committee (DMC) has reviewed the safety data from the first two groups of patients treated and found no problems or adverse side effects. One group of three patients was given 2 million cells. The second group of five patients received 10 million cells. Asterias is now cleared to enroll another 5-8 patients with 20 million cells. The SciStar study, funded in part by the California Institute for Regenerative Medicine (CIRM) is a Phase 1/2a clinical trial that is designed to test first the safety and then the effectiveness of Asterias’ AST-OPC1 cells. These are a form of cells called oligodendrocyte progenitors, which are capable of becoming several different kinds of cells some of which play a supporting role and help protect nerve cells in the central nervous system, including areas of the spinal cord that are damaged in spinal cord injury. “Our focus is always on the patient, so making sure a potential therapy is safe is an important first step,” says C. Randal Mills, Ph.D., the President and CEO of CIRM. “I recently met with Jake Javier, a young man who was treated in this trial, and heard first-hand what he and his family are going through in the aftermath of his injury. But I also saw a young man with remarkable courage and determination. It is because of Jake, and the others who volunteer to take part in [...]

From labs to lives: Self-replicating cells help treat neuro disorders

July 27, 2016 Scientists estimate that human bodies contain anywhere from 75 to 100 trillion cells. And of these cells, there are hundreds of different types. Yet, one cell type in particular has captured the fascination of assistant professor David Brafman: the human pluripotent stem cell (hPSC).Assistant professor David Brafman mentoring biomedical engineering junior Lexi Bounds, who plans to pursue a career in stem cell research. Photographer: Jessica Hochreiter/ASU As self-replicating cells — capable of dividing and forming new cells — hPSCs offer immense research potential. They are able to provide the raw material needed to generate the hundreds of different cell types that comprise the human body. Think of it as a reverse e pluribus unum. Something like out of one, come many. Brafman has received a $420,000 grant from the National Institutes of Health to take discoveries related to hPSCs out of the research lab and into the clinical setting where they can transform, even save, lives. In particular, his research focuses on using the remarkable qualities of hPSCs to generate large quantities of hPSC-derived neurons, which are instrumental in advances toward the study and treatment of Alzheimer’s disease, ALS, spinal cord injuries and other neurodegenerative disorders. “Neurodegenerative diseases and disorders remain some of the leading causes of mortality and morbidity in the United States,” said Brafman, a biomedical engineering faculty member in ASU’s Ira A. Fulton Schools of Engineering. According to the Alzheimer’s Association, the disease affects more than 130,000 individuals statewide and is the fifth leading cause of death in Arizona. “Several bottlenecks limit the translation of hPSCs and their derivatives from bench to bedside,” said Brafman, referring to the need to take this research from the laboratory bench to the clinical [...]

Spinal cord injury repair requires scars

April 19, 2016 At a Glance A study in mice suggests that scar formation may help, not hinder, nerve regrowth after spinal cord injury. The findings, which contradict previous dogma, could lead to new strategies to encourage nerve fibers to regrow across spinal lesions. Previously injured axons (red) can grow through a dense astrocyte scar (green) in the presence of molecules that stimulate growth (blue). Dr. Michael V. Sofroniew, UCLA Spinal cord injuries can occur after a sudden, traumatic blow to the spine. Most injuries don’t completely sever the spinal cord, but instead fracture or compress the vertebrae. This damage can crush and destroy axons—the nerve cell extensions that carry signals up and down the spinal cord between the brain and the rest of the body. If this communication pathway can’t be repaired, spinal cord damage can cause serious disability, including paralysis. When the spinal cord is damaged, specialized cells head to the injury site and form a scar. For decades, researchers believed that scar-forming cells called astrocytes prevented neuronal regrowth at sites of spinal cord injury. Therefore, a team led by Dr. Michael V. Sofroniew at the University of California, Los Angeles, investigated whether blocking astrocyte scars from forming or removing them once they’ve formed would allow neurons to regrow. The research was funded in part by NIH’s National Institute of Neurological Disorders and Stroke (NINDS) and National Institute of Mental Health (NIMH). Results were published on April 14, 2016, in Nature. Using genetically modified mouse models, the researchers removed either astrocyte cells or the chemical signal they release, STAT3. Both are necessary components for astrocyte scar formation. The team then measured the regrowth of 3 different types of neurons—coming from the brain, the [...]

Scientists use stem cells to regrow spinal cords

Research on rats could one day help paralyzed humans 29.03.2016 By Barry Eitel SAN FRANCISCO Scientists announced Tuesday that they have successfully regenerated the spinal cords of paralyzed rats using stem cells, a breakthrough that the researchers hope will lead to human trials. Researchers built tiny patches of stem cells collected from rats and humans. They then placed the patches on the broken spinal cords of rats. With the patches, the rodents once again reached out and grabbed food with their paws. Though scientists have been able to regenerate certain nerve cells from stem cells, this is the first time a crucially important set of nerves, called the corticospinal axons, have been grown. The cells build a vast web of biological wiring, called the corticospinal projection, which sends information between the brain and the body. They are crucial for voluntary movement in humans. Conducted by scientists working in California, Wisconsin and Japan, the research was published in the journal Nature Medicine. “The corticospinal projection is the most important motor system in humans,” said senior study author Mark Tuszynski of the University of California, San Diego. “It has not been successfully regenerated before. Many have tried, many have failed – including us, in previous efforts.” The corrective patches were made from neural projector cells, a type of stem cell that can form multiple kinds of the different cells that comprise the central nervous system in humans and other mammals, including rats. By using different chemicals, researchers were able to coax the neural cells into becoming useable spinal cord tissue. “The new thing here was that we used neural stem cells for the first time to determine whether they, unlike any other cell type tested, would support regeneration,” [...]

Engineering a spinal cord repair kit

Feb. 29, 2016 New, multifunctional fibers to help repair nerve damage or deliver treatment for mental, neurological disorders Polina Anikeeva hopes to one day be able to regenerate the spinal cord to restore movement for paralyzed people or possibly bypass the spinal cord altogether with a device that mimics its function. With support from the National Science Foundation (NSF), the materials scientist and her team at the Massachusetts Institute of Technology (MIT) are engineering a nerve repair "tool kit," with an eye toward repairing damaged nerves and even growing new ones. They're designing multifunctional polymer strands -- thinner than a human hair -- that would be implanted right alongside damaged neurons. The strands can have hollow channels to deliver drugs, embedded electrodes to send electrical signals, or optical guides to transmit light for optogenetics, a method for switching nerve signals on and off. The team is also designing fibers that can act as tiny scaffolds or 3-D structures, to support new nerve tissue as it grows or even accelerate the growth. The ultimate goal is to help doctors treat diseases such as Parkinson's, schizophrenia and depression, in addition to healing spinal injuries. Anikeeva's research helps advance NSF's efforts to enable scientific understanding of the full complexity of the brain, in action and in context. The research in this episode was supported by NSF award #1253890, Optoelectronic neural scaffolds: materials platform for investigation and control of neuronal activity and development. This was a Faculty Early Career Development Program (CAREER) award. Click here to watch video Miles O'Brien, Science Nation Correspondent Ann Kellan, Science Nation Producer

Master gene orchestrates regeneration of damaged peripheral nerves​

October 29, 2015 CAVALLI LABORATORY PHOTO To study how peripheral neurons regrow axons — the branches of nerve cells that transmit nerve signals — researchers at Washington University School of Medicine in St. Louis grow them in a dish, cut them (as shown) and observe how they regrow. The researchers, led by Valeria Cavalli, PhD, have identified a master gene that enables repair of these branches when they are cut. One of the big challenges with spinal cord injuries is that spinal cord neurons don’t have the ability to regrow after an injury. That’s why most spinal paralysis in patients is permanent. So scientists tend to focus their research on regrowing peripheral neurons – those that extend from the spinal column to the tips of the hands and feet. Peripheral neurons in the body’s extremities have the ability to regenerate, helping people regain some movement and sensation. In new research, scientists at Washington University School of Medicine in St. Louis have identified a master gene involved in orchestrating the regrowth of peripheral nerves. The gene works as a main switch, making other genes “flip on” in a domino-like fashion. Understanding how these nerves regenerate one day may aid efforts to regrow spinal cord neurons, the researchers said. The findings are published online Oct. 29 in the journal Neuron. Surprisingly, senior author Valeria Cavalli, PhD, associate professor of neurobiology, has shown that injury to peripheral nerves flips on a master gene, called hypoxia-inducible factor 1-alpha, otherwise known as HIF-1alpha. This gene, in turn, activates some 200 genes involved in the regrowth of peripheral nerves.​​​​​​​​​​​​​​ Follow the School of Medicine Facebook @WUSTLmed Google+ “What is interesting about HIF-1alpha is that it is known to be sensitive to [...]

Surgeons restore hand, arm movement to quadriplegic patients

Innovative technique helps patients with neck injuries October 8, 2015 By Kristina Sauerwein  A pioneering surgical technique has restored some hand and arm movement to patients immobilized by spinal cord injuries in the neck, reports a new study at Washington University School of Medicine in St. Louis. Like railroad switchmen, the focus is on rerouting passageways; however, instead of trains on a track, the surgeons redirect peripheral nerves in a quadriplegic’s arms and hands by connecting healthy nerves to the injured nerves. Essentially, the new nerve network reintroduces conversation between the brain and the muscles that allows patients, once again, to accomplish tasks that foster independence, such as feeding themselves or writing with a pen. The researchers assessed outcomes of nerve-transfer surgery in nine quadriplegic patients with spinal cord injuries in the neck. Every patient in the study reported improved hand and arm function. The study is published in the October issue of the American Society of Plastic Surgeons’ journal Plastic and Reconstructive Surgery. “Physically, nerve-transfer surgery provides incremental improvements in hand and arm function. However, psychologically, these small steps are huge for a patient’s quality of life,” said the study’s lead author, Ida K. Fox, MD, assistant professor of plastic and reconstructive surgery. “One of my patients told me he was able to pick up a noodle off his chest when he dropped it.’ Before the surgery, he couldn’t move his fingers. It meant a lot for him to clean off that noodle without anyone helping him.” Soft nerve bundles form the human spinal cord, which acts as the body’s control tower by communicating to the brain physical activities both large and small. The cervical spinal cord, in the neck, is comprised of seven [...]