Presence of Enzyme May Worsen Effects of Spinal Cord Injury and Impair Long-term Recovery

Traumatic spinal cord injury (SCI) is a devastating condition with few treatment options. Studies show that damage to the barrier separating blood from the spinal cord can contribute to the neurologic deficits that arise secondary to the initial trauma. Through a series of sophisticated experiments, researchers reporting in The American Journal of Pathology suggest that matrix metalloproteinase-3 (MMP-3) plays a pivotal role in disruption of the brain/spinal cord barrier (BSCB), cell death, and functional deficits after SCI. This link also presents new therapeutic possibilities.

“Matrix metalloproteinases (MMPs) are enzymes known to degrade the extracellular matrix and other extracellular proteins and are essential for remodeling of the extracellular matrix and wound healing. Excessive proteolytic activity of MMPs can be detrimental, leading to numerous pathological conditions, including blood brain barrier (BBB)/BSCB disruption after injury,” explains Tae Young Yune, PhD, of the Department of Biochemistry and Molecular Biology, School of Medicine, Kyung Hee University, Seoul, Korea. Although other MMPs have been linked to SCI (i.e. MMP-2, MMP-9, and MMP-12), there has been no previous direct evidence of a similar role for MMP-3.

By comparing mice that underwent spinal cord injury to a control group, investigators found that both MMP3 messenger RNA (mRNA) and MMP-3 protein levels in spinal cord segments were increased after SCI, peaking one day after surgery in the experimental group, whereas no changes were seen in the controls. MMP-3 immunoreactivity was detected in cells within the lesion site, invading neutrophils, and blood vessel endothelial cells in the area outside of the initial injured area (the penumbra).

Another series of experiments focused on the role of MMP-3 in BSCB permeability, using dye to visualize leakage through the BSCB. Similar to MMP-3 mRNA and protein levels, dye leakage reached a maximum one day after SCI. Leakage was lower in Mmp3 knockout mice that were genetically altered to be deficient in MMP-3 as well as in mice injected with either Mmp3 small interfering RNA (siRNA) or a general MMP inhibitor. Injection of MMP-3 into normal spinal cord also significantly increased dye leakage.

MMP-3 was found to contribute to the degradation of tight junction proteins that are responsible for maintaining the integrity of the BSCB barrier. In addition, the researchers reported that MMP-3 induced blood cell infiltration and hemorrhage after SCI in wild-type mice, but not in Mmp3 knockout mice.  MMP-3 also mediated activation of other MMPs (MMP-2 and MMP-9) that are up-regulated after SCI. “This is the first study to demonstrate that MMP-3 is involved in MMP-9 activation in central nervous system injury,” says Dr. Yune.

A significant finding was that mice deficient in MMP-3 showed significantly better functional recovery 14 and 28 days after injury than non-deficient mice. Histological analysis showed that after SCI the mice deficient in MMP-3 had smaller volumes of injured tissue and more healthy axons than non-deficient wild-type mice.

“The evidence suggests that BBB/BSCB disruption plays a pivotal role in acute and chronic neurological disorders. The inhibition of MMP-3 may be a promising therapeutic target for human central nervous system disease, including SCI,” notes Dr. Yune.

From Rats to Humans: Project NEUWalk Closer to Clinical Trials

EPFL scientists have discovered how to control the limbs of a completely paralyzed rat in real time to help it walk again. Their results are published today in Science Translational Medicine.

Building on earlier work in rats, this new breakthrough is part of a more general therapy that could one day be implemented in rehabilitation programs for people with spinal cord injury, currently being developed in a European project called NEUWalk. Clinical trials could start as early as next summer using the new Gait Platform, built with the support of the Valais canton and the SUVA, and now assembled at the CHUV (Lausanne University Hospital).

How it works

The human body needs electricity to function. The electrical output of the human brain, for instance, is about 30 watts. When the circuitry of the nervous system is damaged, the transmission of electrical signals is impaired, often leading to devastating neurological disorders like paralysis.

Electrical stimulation of the nervous system is known to help relieve these neurological disorders at many levels. Deep brain stimulation is used to treat tremors related to Parkinson’s disease, for example. Electrical signals can be engineered to stimulate nerves to restore a sense of touch in the missing limb of amputees. And electrical stimulation of the spinal cord can restore movement control in spinal cord injury.

But can electrical signals be engineered to help a paraplegic walk naturally? The answer is yes, for rats at least.

“We have complete control of the rat’s hind legs,” says EPFL neuroscientist Grégoire Courtine. “The rat has no voluntary control of its limbs, but the severed spinal cord can be reactivated and stimulated to perform natural walking. We can control in real-time how the rat moves forward and how high it lifts its legs.”

The scientists studied rats whose spinal cords were completely severed in the middle-back, so signals from the brain were unable to reach the lower spinal cord. That’s where flexible electrodes were surgically implanted. Sending electric current through the electrodes stimulated the spinal cord.

They realized that there was a direct relationship between how high the rat lifted its limbs and the frequency of the electrical stimulation. Based on this and careful monitoring of the rat’s walking patterns – its gait – the researchers specially designed the electrical stimulation to adapt the rat’s stride in anticipation of upcoming obstacles, like barriers or stairs.

“Simple scientific discoveries about how the nervous system works can be exploited to develop more effective neuroprosthetic technologies,” says co-author and neuroengineer Silvestro Micera. “We believe that this technology could one day significantly improve the quality of life of people confronted with neurological disorders.”

Taking this idea a step further, Courtine and Micera together with colleagues from EPFL’s Center for Neuroprosthetics are also exploring the possibility of decoding signals directly from the brain about leg movement and using this information to stimulate the spinal cord.

Towards clinical trials using the Gait Platform at the CHUV

The electrical stimulation reported in this study will be tested in patients with incomplete spinal cord injury in a clinical study that may start as early as next summer, using a new Gait Platform that brings together innovative monitoring and rehabilitation technology.

Designed by Courtine’s team, the Gait Platform consists of custom-made equipment like a treadmill and an overground support system, as well as 14 infrared cameras that detect reflective markers on the patient’s body and two video cameras, all of which generate extensive amounts of information about leg and body movement. This information can be fully synchronized for complete monitoring and fine-tuning of the equipment in order to achieve intelligent assistance and adaptive electrical spinal cord stimulation of the patient.

The Gait Platform is housed in a 100 square meter room provided by the CHUV. The hospital already has a rehabilitation center dedicated to translational research, notably for orthopedic and neurological pathologies.

“The Gait Platform is not a rehabilitation center,” says Courtine. “It is a research laboratory where we will be able to study and develop new therapies using very specialized technology in close collaboration with medical experts here at the CHUV, like physiotherapists and doctors.”

New research offers help for spinal cord patients

In a study on rats, researchers at the University of Copenhagen have discovered the cause of the involuntary muscle contractions which patients with severe spinal cord injuries frequently suffer. The findings have just been published in the Journal of Neuroscience and, in the long run, can pave the way for new treatment methods.

Three thousand Danish patients suffer from severe spinal cord injuries after being involved in traffic accidents or accidents at work. An injury to the spinal cord is a catastrophe for the individual, and often results in complete or partial paralysis of the person’s arms and legs. Despite the paralysis, several patients experience problems with involuntary muscle contractions or spasms which impair the patient’s quality of life.

The movements are due to the neurotransmitter serotonin, which normally plays a crucial role in relation to our voluntary control of movements by reinforcing the level of activity in the motor neurones when they have to activate the muscles to an extraordinary degree. Research shows that a group of cells in the spinal cord start supplying serotonin in an uncontrolled way following an injury, and this knocks the motor system out of control.

“We now have a qualified idea of why the serotonin level goes out of control, and we have documented that a special serotonin-producing enzyme plays a key role. By targeting the specific enzyme, in the long term we will be able to devise new methods of treatment when we are trying to impact functions in the nervous system,” says associate professor and neurophysiologist Jacob Wienecke.

The prospects of the study are interesting for both spinal cord patients and patients suffering from Parkinson’s disease.

Emergency response kicks in

The enzyme aromatic L-amino acid decarboxylase (AADC) plays an important role in the production of the neurotransmitter serotonin:

“In the first few days after an injury to the spinal cord, we can see there is a very rapid regulation of AADC which results in the uncontrolled production of serotonin. It is our guess that this is the spinal cord’s emergency response trying to boost the enzyme’s capacity,” says Jacob Wienecke.

According to the researchers, it may be the same emergency response which causes the involuntary movements – dyskinesia – that are also experienced by patients with Parkinson’s disease. However, for Parkinson’s patients, it is the dopamine system which is affected, but the enzyme which activates the emergency response is the same.

“It is an interesting perspective, which will hopefully focus efforts on targeting drugs specifically at the AADC cells. Perhaps in the future we can regulate the undesired neural activity in this way so that the unnecessary ‘disturbance on the line’ disappears for the affected patients,” says Jacob Wienecke.

Existing treatment puts a damper on learning

Existing forms of treatment for spinal cord patients currently involve, for example, using the drug baclofen, which suppresses neural activity, and thereby the motor neurones which cause the involuntary movements. The problem with baclofen though is that it impacts motor learning – and thus the patients’ rehabilitation. However, there is still a long way to go. Developing new drugs is a protracted process, and the way is paved with obstacles. Injuries to the spinal column are extremely complex, and primarily result in interruptions to the signalling between the brain and the body.

“Finding a solution to the problem is no easy task. However, a lot suggests that regulating serotonin production more precisely could mitigate undesirable spasms while also supporting the rehabilitation of controlled movements. So far, the study has been carried out on rats, but we have reason to believe that the same mechanisms apply in humans,” says Jacob Wienecke in conclusion.

(Image caption: This image shows an artificial connection that connects brain to spinal circuits. Credit: © Yukio Nishimura)

Bypass commands from the brain to legs through a computer

Gait disturbance in individuals with spinal cord injury is attributed to the interruption of neural pathways from brain to the spinal locomotor center, whereas neural circuits locate below and above the lesion maintain most of their functions. An artificial connection that bridges the lost pathway and connects brain to spinal circuits has potential to ameliorate the functional loss. A Japanese research group led by Shusaku Sasada, research fellow and Yukio Nishimura, associate professor of the National Institute for Physiological Sciences (NIPS), National Institutes of Natural Sciences (NINS) has successfully made an artificial connection from the brain to the locomotion center in the spinal cord by bypassing with a computer interface. This allowed subjects to stimulate the spinal locomotion center using volitionally-controlled muscle activity and to control walking in legs. This result was published online in The Journal of Neuroscience on August 13, 2014.

Neural networks in the spinal cord, locomotion center are capable of producing rhythmic movements, such as swimming and walking, even when isolated from the brain. The brain controls spinal locomotion center by sending command to the spinal locomotion center to start, stop and change waking speed. In most cases of spinal cord injury, the loss of this link from the brain to the locomotion center causes problems with walking.

The research group came up with bypassing the functioning brain and locomotion center with the computer to compensate lost pathways as a way to enable individuals with spinal cord injury to regain walking ability.

Since the arm movement associate with leg movement when we walk they used muscle activity of arm to sarogate the brain activity. The computer interface allowed subjects to control magnetic stimulator that drive to the spinal locomotion center non-invassively using volitionally-controlled muscle activity and to control walking in legs. As a results of experiments in people who are neurologically intact, the subjects were asked to make own legs relaxed and passively controlled via computer interface that was controlled by arm muscle, walking behavior in legs was induced and subjects could control the step cycle volitionally as well. However without bypassing with the computer interface, the legs did not move even if the arms muscle was volitionally acivated.

"We hope that this technology would compensate for the interrupted pathways’ function by sending an intentionally encoded command to the preserved spinal locomotor center and regain volitionally-controlled walking in indviduals with paraplegia. However, the major challenge that this technology does not help them to dodge obstacles and to maintain posture. We are carefully working toward clinical application in near future", Nishimura said.

(Image caption: The presence of p45 (green staining) and p75 (red staining) indicates that motor neurons increase both p45 and p75 expression after sciatic nerve injury in an animal. Image credit: Courtesy of the Salk Institute for Biological Studies)

Scientists uncover new clues to repairing an injured spinal cord

Frogs, dogs, whales, snails can all do it, but humans and primates can’t. Regrow nerves after an injury, that is—while many animals have this ability, humans don’t. But new research from the Salk Institute suggests that a small molecule may be able to convince damaged nerves to grow and effectively rewire circuits. Such a feat could eventually lead to therapies for the thousands of Americans with severe spinal cord injuries and paralysis.

"This research implies that we might be able to mimic neuronal repair processes that occur naturally in lower animals, which would be very exciting," says the study’s senior author and Salk professor Kuo-Fen Lee. The results were published today in PLOS Biology.

For a damaged nerve to regain function, its long, signal-transmitting extensions known as axons need to grow and establish new connections to other cells.

In a study published last summer in PLOS ONE, Lee and his colleagues found that the protein p45 promotes nerve regeneration by preventing the axon sheath (known as myelin) from inhibiting regrowth. However, humans, primates and some other more advanced vertebrates don’t have p45. Instead, the researchers discovered a different protein, p75, that binds to the axon’s myelin when nerve damage occurs in these animals. Instead of promoting nerve regeneration, p75 actually halts growth in damaged nerves.

"We don’t know why this nerve regeneration doesn’t occur in humans. We can speculate that the brain has so many neural connections that this regeneration is not absolutely necessary," Lee says.

In the study published today, the scientists looked at how two p75 proteins bind together and form a pair that latches onto the inhibitors released from damaged myelin.

By studying the configurations of the proteins in solutions using nuclear magnetic resonance (NMR) technology, the researchers found that the growth-promoting p45 could disrupt the p75 pairing.

"For reasons that are not understood, when p45 comes in, it breaks the pair apart," says Lee, holder of the Helen McLoraine Chair in Molecular Neurobiology.

What’s more, the p45 protein was able to bind to the specific region in the p75 protein that is critical for the formation of the p75 pair, thus decreasing the amount of p75 pairs that bond to inhibitors release from myelin. With less p75 pairs available to bond to inhibitor signals, axons were able to regrow.

The findings suggest that an agent—either p45 or another disrupting molecule—that can effectively break the p75 pair could offer a possible therapy for spinal cord damage.

One method of therapy could be to introduce more p45 protein to injured neurons, but a smarter tactic might be to introduce a small molecule that jams the link between the two p75 proteins, Lee says. “Such an agent could possibly get through the blood-brain barrier and to the site of spinal cord injuries,” he says.

The next step will be to see if introducing p45 helps regenerate damaged human nerves. “That is what we hope to do in the future,” Lee says.

Controlling movement with light

For the first time, MIT neuroscientists have shown they can control muscle movement by applying optogenetics — a technique that allows scientists to control neurons’ electrical impulses with light — to the spinal cords of animals that are awake and alert.  

Led by MIT Institute Professor Emilio Bizzi, the researchers studied mice in which a light-sensitive protein that promotes neural activity was inserted into a subset of spinal neurons. When the researchers shone blue light on the animals’ spinal cords, their hind legs were completely but reversibly immobilized. The findings, described in the June 25 issue of PLoS One, offer a new approach to studying the complex spinal circuits that coordinate movement and sensory processing, the researchers say.

In this study, Bizzi and Vittorio Caggiano, a postdoc at MIT’s McGovern Institute for Brain Research, used optogenetics to explore the function of inhibitory interneurons, which form circuits with many other neurons in the spinal cord. These circuits execute commands from the brain, with additional input from sensory information from the limbs.

Previously, neuroscientists have used electrical stimulation or pharmacological intervention to control neurons’ activity and try to tease out their function. Those approaches have revealed a great deal of information about spinal control, but they do not offer precise enough control to study specific subsets of neurons.

Optogenetics, on the other hand, allows scientists to control specific types of neurons by genetically programming them to express light-sensitive proteins. These proteins, called opsins, act as ion channels or pumps that regulate neurons’ electrical activity. Some opsins suppress activity when light shines on them, while others stimulate it.

“With optogenetics, you are attacking a system of cells that have certain characteristics similar to each other. It’s a big shift in terms of our ability to understand how the system works,” says Bizzi, who is a member of MIT’s McGovern Institute.

Muscle control

Inhibitory neurons in the spinal cord suppress muscle contractions, which is critical for maintaining balance and for coordinating movement. For example, when you raise an apple to your mouth, the biceps contract while the triceps relax. Inhibitory neurons are also thought to be involved in the state of muscle inhibition that occurs during the rapid eye movement (REM) stage of sleep.

To study the function of inhibitory neurons in more detail, the researchers used mice developed by Guoping Feng, the Poitras Professor of Neuroscience at MIT, in which all inhibitory spinal neurons were engineered to express an opsin called channelrhodopsin 2. This opsin stimulates neural activity when exposed to blue light. They then shone light at different points along the spine to observe the effects of neuron activation.

When inhibitory neurons in a small section of the thoracic spine were activated in freely moving mice, all hind-leg movement ceased. This suggests that inhibitory neurons in the thoracic spine relay the inhibition all the way to the end of the spine, Caggiano says. The researchers also found that activating inhibitory neurons had no effect on the transmission of sensory information from the limbs to the brain, or on normal reflexes.

“The spinal location where we found this complete suppression was completely new,” Caggiano says. “It has not been shown by any other scientists that there is this front-to-back suppression that affects only motor behavior without affecting sensory behavior.”

“It’s a compelling use of optogenetics that raises a lot of very interesting questions,” says Simon Giszter, a professor of neurobiology and anatomy at Drexel University who was not part of the research team. Among those questions is whether this mechanism behaves as a global “kill switch,” or if the inhibitory neurons form modules that allow for more selective suppression of movement patterns.

Now that they have demonstrated the usefulness of optogenetics for this type of study, the MIT team hopes to explore the roles of other types of spinal cord neurons. They also plan to investigate how input from the brain influences these spinal circuits.

“There’s huge interest in trying to extend these studies and dissect these circuits because we tackled only the inhibitory system in a very global way,” Caggiano says. “Further studies will highlight the contribution of single populations of neurons in the spinal cord for the control of limbs and control of movement.”

Researchers find new target for chronic pain treatment

Researchers at the UNC School of Medicine have found a new target for treating chronic pain: an enzyme called PIP5K1C. In a paper published today in the journal Neuron, a team of researchers led by Mark Zylka, PhD, Associate Professor of Cell Biology and Physiology, shows that PIP5K1C controls the activity of cellular receptors that signal pain.

By reducing the level of the enzyme, researchers showed that the levels of a crucial lipid called PIP₂ in pain-sensing neurons is also lessened, thus decreasing pain.

They also found a compound that could dampen the activity of PIP5K1C. This compound, currently named UNC3230, could lead to a new kind of pain reliever for the more than 100 million people who suffer from chronic pain in the United States alone.

In particular, the researchers showed that the compound might be able to significantly reduce inflammatory pain, such as arthritis, as well as neuropathic pain – damage to nerve fibers. The latter is common in conditions such as shingles, back pain, or when bodily extremities become numb due to side effects of chemotherapy or diseases such as diabetes.

The creation of such bodily pain might seem simple, but at the cellular level it’s quite complex. When we’re injured, a diverse mixture of chemicals is released, and these chemicals cause pain by acting on an equally diverse group of receptors on the surface of pain-sensing neurons.

“A big problem in our field is that it is impractical to block each of these receptors with a mixture of drugs,” said Zylka, the senior author of the Neuron article and member of the UNC Neuroscience Center. “So we looked for commonalities – things that each of these receptors need in order to send a signal.” Zylka’s team found that the lipid PIP₂ (phosphatidylinositol 4,5-bisphosphate) was one of these commonalities.

“So the question became: how do we alter PIP₂ levels in the neurons that sense pain?” Zylka said. “If we could lower the level of PIP₂, we could get these receptors to signal less effectively. Then, in theory, we could reduce pain.”

Many different kinases can generate PIP₂ in the body.  Brittany Wright, a graduate student in Zylka’s lab, found that the PIP5K1C kinase was expressed at the highest level in sensory neurons compared to other related kinases. Then the researchers used a mouse model to show that PIP5K1C was responsible for generating at least half of all PIP₂ in these neurons.

“That told us that a 50 percent reduction in the levels of PIP5K1C was sufficient to reduce PIP₂ levels in the tissue we were interested in – where pain-sensing neurons are located” Zylka said. “That’s what we wanted to do – block signaling at this first relay in the pain pathway.”

Once Zylka and colleagues realized that they could reduce PIP₂ in sensory neurons by targeting PIP5K1C, they teamed up with Stephen Frye, PhD, the Director of the Center for Integrative Chemical Biology and Drug Discovery at the UNC Eshelman School of Pharmacy.

They screened about 5,000 small molecules to identify compounds that might block PIP5K1C. There were a number of hits, but UNC3230 was the strongest. It turned out that Zylka, Frye, and their team members had come upon a drug candidate. They realized that the chemical structure of UNC3230 could be manipulated to potentially turn it into an even better inhibitor of PIP5K1C. Experiments to do so are now underway at UNC.

Newborns a hope for spinal injuries

It all started at a symposium five years ago. Catherine Gorrie, an expert in spinal cord injury, was listening to a presentation about the differences between the developing brains of children and the mature ones of adults when she had an “aah-haa” moment.

“I began to wonder if there is something in the spines of children that could be manipulated for repair,” says Dr Gorrie, a neuroscientist at the University of Technology, Sydney (UTS). It made sense. Dr Gorrie already knew that the more adaptable, or “plastic”, spinal cords of infants responded more efficiently to injury than did those of adults.

If she could tease out the factors that encouraged generic cells, so-called stem cells, in the spines of newborns to become new nerve cells, neurones, Dr Gorrie reasoned that it should be possible to mimic the process and help repair spinal cord injuries in people of all ages. That would be incredibly important because, to date, there is no cure for spinal cord injury and no proven drug treatment.

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Hope for paraplegic patients

People with severe injuries to their spinal cord currently have no prospect of recovery and remain confined to their wheelchairs. Now, all that could change with a new treatment that stimulates the spinal cord using electric impulses. The hope is that the technique will help paraplegic patients learn to walk again. From June 3 – 5, Fraunhofer researchers will be at the Sensor + Test measurement fair in Nürnberg to showcase the implantable microelectrode sensors they have developed in the course of pre-clinical development work (Hall 12, Booth 12-537).

Thomas T. was just 25 years old when a severe motorcycle accident changed his life in an instant. Doctors diagnosed him with paraplegia following an injury to his spinal cord in the lumbar region. The young man has been confined to a wheelchair ever since. The diagnosis of paraplegia came as a shock, and it was only in the course of a month-long period of rehabilitation that Thomas T. was able to come to terms with his condition. Patients like him currently have no prospect of recovery, as there is still no effective course of treatment available for improving motor function among the severely disabled.

Now a consortium of European research institutions and companies want to get affected patients quite literally back on their feet. In the EU’s NEUWalk project, which has been awarded funding of some nine million euros, researchers are working on a new method of treatment designed to restore motor function in patients who have suffered severe injuries to their spinal cord. The technique relies on electrically stimulating the nerve pathways in the spinal cord. “In the injured area, the nerve cells have been damaged to such an extent that they no longer receive usable information from the brain, so the stimulation needs to be delivered beneath that,” explains Dr. Peter Detemple, head of department at the Fraunhofer Institute for Chemical Technology’s Mainz branch (IMM) and NEUWalk project coordinator. To do this, Detemple and his team are developing flexible, wafer-thin microelectrodes that are implanted within the spinal canal on the spinal cord. These multichannel electrode arrays stimulate the nerve pathways with electric impulses that are generated by the accompanying by microprocessor-controlled neurostimulator. “The various electrodes of the array are located around the nerve roots responsible for locomotion. By delivering a series of pulses, we can trigger those nerve roots in the correct order to provoke motion sequences of movements and support the motor function,” says Detemple.

Researchers from the consortium have already successfully conducted tests on rats in which the spinal cord had not been completely severed. As well as stimulating the spinal cord, the rats were given a combination of medicine and rehabilitation training. Afterwards the animals were able not only to walk but also to run, climb stairs and surmount obstacles. “We were able to trigger specific movements by delivering certain sequences of pulses to the various electrodes implanted on the spinal cord,” says Detemple. The research scientist and his team believe that the same approach could help people to walk again, too. “We hope that we will be able to transfer the results of our animal testing to people. Of course, people who have suffered injuries to their spinal cord will still be limited when it comes to sport or walking long distances. The first priority is to give them a certain level of independence so that they can move around their apartment and look after themselves, for instance, or walk for short distances without requiring assistance,” says Detemple.

Researchers from the NEUWalk project intend to try out their system on two patients this summer. In this case, the patients are not completely paraplegic, which means there is still some limited communication between the brain and the legs. The scientists are currently working on tailored implants for the intervention. “However, even if both trials are a success, it will still be a few years before the system is ready for the general market. First, the method has to undergo clinical studies and demonstrate its effectiveness among a wider group of patients,” says Detemple.

Electric spinal cord stimulation to offer relief for Parkinson’s disease

Patients with Parkinson’s disease could also benefit from the neural prostheses. The most well-known symptoms of the disease are trembling, extreme muscle tremors and a short, stooped gait that has a profound effect on patients’ mobility. Until now this neurodegenerative disorder has mostly been treated with dopamine agonists – drugs that chemically imitate the effects of dopamine but that often lead to severe side effects when taken over a longer period of time. Once the disease has reached an advanced stage, doctors often turn to deep brain stimulation. This involves a complex operation to implant electrodes in specific parts of the brain so that the nerve cells in the region can be stimulated or suppressed as required. In the NEUWalk project, researchers are working on electric spinal cord simulation – an altogether less dangerous intervention that should however ease the symptoms of Parkinson’s disease just as effectively. “Initial animal testing has yielded some very promising results,” says Detemple.

The researchers from Mainz will be at the Sensor + Test 2014 measurement fair in Nürnberg to showcase their neural prostheses. These include implantable microelectrode sensors controlled by microprocessors as well as rigid multi-channel sensors that can be used to record electrophysiological signals and to stimulate neural structures.