Posts tagged parkinson's disease
Articles and news from the latest research reports.
Forget Smart Watches, ‘Smart Skin’ May Be the Next Big Thing in Wearable Computers
Parkinson’s patients could one day ditch their pills for a stretchy skin patch with a mind of its own. Using specialized sensors, the patch would monitor the wearer’s vital signs, beam the information to a doctor, and administer medication as needed. While such devices still face substantial obstacles before wide-scale implementation, two teams of researchers have announced innovations combining standard electronics with flexible materials that may bring the futuristic concept closer to reality.
Conventional electronics, such as those found in computers and smartphones, are built on stiff slabs of silicon. While durable, the design makes for bulky and uncomfortable wearable devices. Flexible electronics instead print circuits onto limber strips of silicone or plastic. The bendable base layers make devices twist and stretch when attached to the skin, but they are limited by a lack of key components such as batteries and processors that currently do not exist in flexible form.
Researchers from Seoul National University led by bioengineer Dae-Hyeong Kim have now developed a patch that automatically delivers medication to Parkinson’s patients. Parkinson’s disease is a neurological disorder that causes movement impairments such as hand tremors that require regular medication to suppress. Typically, patients take pills every few hours, leading to a spike in medication levels followed by a gradual decline that causes the tremors to return. The team’s skin patch instead supplies a series of smaller measured doses as needed by using a tremor-detecting sensor. Because the device needs to track the tremors over time, they utilized a newly invented memory format called resistive random-access memory to create the first flexible data storage for wearable devices. The new format can be used in a thin, low-power form, making it ideal for inclusion in wearable electronics.
Muscle paralysis eased by light-sensitive stem cells
A genetic tweak can make light work of some nervous disorders. Using flashes of light to stimulate modified neurons can restore movement to paralysed muscles. A study demonstrating this, carried out in mice, lays the path for using such “optogenetic” approaches to treat nerve disorders ranging from spinal cord injury to epilepsy and motor neuron disease.
Optogenetics has been hailed as one of the most significant recent developments in neuroscience. It involves genetically modifying neurons so they produce a light-sensitive protein, which makes them “fire”, sending an electrical signal, when exposed to light.
So far optogenetics has mainly been used to explore how the brain works, but some groups are exploring using it as therapy. One stumbling block has been fears about irreversibly genetically manipulating the brain.
In the latest study, a team led by Linda Greensmith of University College London altered mouse stem cells in the lab before transplanting them into nerves in the leg – this means they would be easier to remove if something went wrong.
"It’s a very exciting approach that has a lot of potential," says Ziv Williams of Harvard Medical School in Boston.
Muscles in action
Greensmith’s team inserted an algal gene that codes for a light-responsive protein into mouse embryonic stem cells. They then added signalling molecules to make the stem cells develop into motor neurons, the cells that carry signals to and from the spinal cord to the rest of the body. They implanted these into the sciatic nerve – which runs from the spinal cord to the lower limbs – of mice whose original nerves had been cut.
After waiting five weeks for the implanted neurons to integrate with the muscle, Greensmith’s team anaesthetised the mice, cut open their skin and shone pulses of blue light on the nerve. The leg muscles contracted in response. “We were surprised at how well this worked,” says Greensmith.
Most current approaches being investigated to help people who are paralysed involve electrically stimulating their nerves or muscles. But this can be painful because they may still have working pain neurons. Plus, the electricity makes the muscles contract too forcefully, making them tire quickly.
Using the optogenetic approach, however, allows the muscle fibres to be stimulated more gently, because the light level can be increased with each pulse. “It gives a very smooth contraction,” says Greensmith.
Breathing restoration
To make the technique practical for use in people, the researchers are developing a light-emitting diode in the form of a cuff that would go around the nerve, which could be connected to a miniature battery pack under the skin.
They are also trying to develop an alternative to using embryonic stem cells, as these would require the recipient to take drugs to stop their immune system attacking the transplanted neurons. Instead the team is working with induced pluripotent stem cells, cells that have been reprogrammed to behave like embryonic stem cells, but can be made from a small sample of the intended recipient’s own skin.
The team’s first goal is to help people with motor neuron disease who lose the ability to control their breathing muscles. “Walking involves contracting about 40 different muscles in complex sequences,” says Greensmith. “Breathing is very simple – one muscle contracts and relaxes.”
They plan to test the restoration of breathing ability in pigs, and are developing a pacemaker that could repeatedly illuminate the phrenic nerve in the chest, which controls the diaphragm.
Other groups are exploring different therapeutic applications of optogenetics, including treatments for epilepsy and Parkinson’s disease
Bioengineer Studying How the Brain Controls Movement
A University of California, San Diego research team led by bioengineer Gert Cauwenberghs is working to understand how the brain circuitry controls how we move. The goal is to develop new technologies to help patients with Parkinson’s disease and other debilitating medical conditions navigate the world on their own. Their research is funded by the National Science Foundation’s Emerging Frontiers of Research and Innovation program.
"Parkinson’s disease is not just about one location in the brain that’s impaired. It’s the whole body. We look at the problems in a very holistic way, combine science and clinical aspects with engineering approaches for technology," explains Cauwenberghs, a professor at the Jacobs School of Engineering and co-director of the Institute for Neural Computation at UC San Diego. "We’re using advanced technology, but in a means that is more proactive in helping the brain to get around some of its problems—in this case, Parkinson’s disease—by working with the brain’s natural plasticity, in wiring connections between neurons in different ways."
Outcomes of this research are contributing to the system-level understanding of human-machine interactions, and motor learning and control in real world environments for humans, and are leading to the development of a new generation of wireless brain and body activity sensors and adaptive prosthetics devices. Besides advancing our knowledge of human-machine interactions and stimulating the engineering of new brain/body sensors and actuators, the work is directly influencing diverse areas in which humans are coupled with machines. These include brain-machine interfaces and telemanipulation.
Uncovering the underlying causes of Parkinson’s disease
A breakthrough investigation by UTS researchers into the underlying causes of Parkinson’s disease has brought us a step closer to understanding how to manage the condition.
The team, led by UTS postdoctoral fellow Dr Dominic Hare and Professor Philip Doble, has produced the first empirical evidence that an imbalance of iron and dopamine in the substantia nigra pars compacta (SNc) region of the brain is the root cause of the neurodegenerative condition.
Caused by the slow loss of neurons in the SNc that control autonomous movement, Parkinson’s disease causes persistent shaking, gastrointestinal problems and a variety of other ailments.
More than 80,000 Australians suffer from the illness, most over the age of 60.
Hare’s findings, before only assumptions in the scientific community, finally validate the theory that iron and dopamine react to create free radicals in the brain that slowly destroy neuron pathways and bring about the onset of Parkinson’s.
"When these two chemicals react, it forms a toxic species of dopamine that essentially reacts like bleach in the brain," said Hare.
To conduct their research Hare and his team used a unique tagging technique using antibodies labelled with gold nanoparticles that acted as proxies for dopamine molecules. This enabled the team to monitor and “co-localise” metals with other molecules and proteins in the brain.
And the findings of this work, said Hare, were revelatory.
"What we found is those particular cells (in the SNc) have what you could call an ‘anti-Goldilocks effect’ – they have just the right amount of iron and just the right amount of dopamine to cause damage," said Dr Hare.
"When we give mice a toxin that mimics the effects of Parkinson’s disease, these cells degenerate."
Hare theorises that this effect is likely a natural result of aging, when the brain’s ability to securely store iron diminishes and allows iron molecules to “leak” into critical areas such as the SNc.
Finding ways to design drugs that can get into the brain and eliminate surplus iron – an initiative that is already well underway in the process of treating other illnesses like cancer and Alzheimer’s disease – is now the next step forward in research.
Preventative measures to halt the build-up of iron in the brain as humans undergo the aging process are also touted by Hare as an important next step, and is something he is now working on.
"I think the real hope is, while we might not necessarily find a cure, prevention is actually not that far away," said Hare.
"So it’s a case where you can wake up and say, ‘my Parkinson’s is flaring up again’, take a tablet and go about your business."
Using your loaf to fight brain disease
Experts analyse baker’s yeast to discover potential for combatting neurological conditions like Parkinson’s and even cancer
A humble ingredient of bread – baker’s yeast – has provided scientists with remarkable new insights into understanding basic processes likely involved in diseases such as Parkinson’s and cancer.
In a new study published in the prestigious journal PNAS (Proceedings of the National Academy of Science), the team from Germany, Leicester, and Portugal detail a new advance – describing for the first time a key feature in cellular development linked to the onset of these devastating diseases.
The research team is from the University Medical Center Goettingen, University of Leicester, and Instituto de Medicina Molecular, Lisbon, directed by long-time collaborators and senior authors Professor Tiago Outeiro and Dr Flaviano Giorgini.
Professor Outeiro, of the University Medical Center Goettingen, Goettingen and Instituto de Medicina Molecular, Lisbon, said: “This work shows how taking advantage of simple model organisms might help us speed up the discovery of more complex biological processes. Yeast cells are really excellent living test tubes, with a powerful toolbox that enabled us to learn about the underpinnings of complex human disorders.”
Dr Giorgini, of the world-renowned Department of Genetics, at the University of Leicester, added: “We are tremendously excited by our results. The family of proteins under investigation have always been a bit of a “black box”, and a true understanding of what these proteins do at a cellular level - and why they are important - has remained elusive. This work provides a step into this darkness.”
The current research takes advantage of the simplicity and genetic power of the baker’s yeast Saccharomyces cerevisiae to understand basic cellular processes underlying Parkinson’s disease. The team studied a family of proteins in yeast (Hsp31, Hsp32, Hsp33, and Hsp34) which are related to a human protein known as DJ-1. Mutations in the human DJ-1 protein cause early-onset inherited forms of Parkinson’s disease, and alterations in the human protein have been associated with more common forms of Parkinson’s disease as well. In addition, changes in DJ-1 function are also associated with certain forms of cancer.
Claire Bale, Research Communications Manager at Parkinson’s UK, commented: “This important research sheds new light on the root causes of Parkinson’s.
“Although mutations in the DJ-1 gene cause rare inherited forms of the condition, we believe that understanding the role of this crucial protein and how it helps keep nerve cells healthy could be important for developing treatments that can help all people with Parkinson’s. We look forward to hearing the results of future investigations in this emerging new area.”
Professor Outeiro continued: “We reasoned that, by studying the yeast cousins of the human protein we would gain important insight into the function these proteins play, and understand why they may cause disease.
Dr Giorgini added: “Though the human protein DJ-1 has been linked to Parkinson’s disease, its central cellular role is not well understood, and thus it is not clear why mutations in this protein cause this devastating disease. Our study sheds new light on what DJ-1 and related proteins are doing at a cellular level, and may thus ultimately have importance for better understanding Parkinson’s.”
The scientists discovered that the yeast versions of the human protein are important for maintenance of normal lifespan of the yeast cell and are involved in regulation of autophagy – a process which the cell employs to breakdown and recycle damaged cellular components. Lifespan and autophagy are central processes in the context of both Parkinson’s disease and cancer. This work is critical because it provides a precise cellular role for DJ-1 family proteins, which links to some of the molecular functions previously ascribed to these proteins. This work could ultimately provide new insight into the mechanisms that contribute to Parkinson’s and cancer.
Leonor Miller-Fleming, of the Instituto de Medicina Molecular, Lisbon and University of Leicester, said: “Our work is important because it suggests that human DJ-1 may function in a similar manner to the yeast version of this protein. We feel that similar studies should be performed with human DJ-1 in nerve cells, to clarify its function and to see if this contributes to the formation of Parkinson’s disease. Ultimately, the detailed understanding of how these proteins function may enable us to come up with novel strategies to treat Parkinson’s disease, cancer, and other related disorders.”
The collaborators believe the next steps in the research are to better understand the details of how the DJ-1 family of proteins regulates autophagy, and if this applies in human neurons, particularly dopaminergic neurons, which are the nerve cells most sensitive to loss in the Parkinson’s brain. Once the researchers build up on the findings they have now described, they will be in a better position to design novel strategies for therapeutic intervention.
Professor Outeiro explained: “This study highlights the importance of international collaborations and networks, in which different strengths are combined to yield novel insights into science. Importantly, this scientific collaboration is also based upon personal friendship between the two senior authors, which makes science ever more exciting and fun.”
Dr Giorgini added: “In addition, this work was primarily spearheaded by a single PhD student – Leonor Miller-Fleming – who drove the project forward with passion and creativity, showing the importance of promoting, supporting and funding doctoral research.”
Professor Outeiro said: “We were pioneers in the development of the first model of Parkinson’s disease in yeast cells. With this work, we explored the powerful toolbox of yeast cells to learn about DJ-1 proteins, also intimately linked to Parkinson’s disease. We are basically adding pieces to this complicated puzzle, and getting one step closer to understanding the origin of this disorder.”
(Image: © Wikipedia)
(Image caption: Various functions of PINK1 within a representative dopaminergic neuron)
New discoveries place lack of energy at the basis of Parkinson’s Disease
Neuroscientists Vanessa Moraïs and Bart De Strooper from VIB and KU Leuven have demonstrated how a defect in the gene Pink1 results in Parkinson’s disease. By mapping this process at a molecular level, they have provided the ultimate proof that a deficient energy production process in cells can result in Parkinson’s disease. These insights are so revolutionary that they have been published in the leading journal Science.
Vanessa Moraïs (VIB/KU Leuven):
“Having Parkinson’s disease means that you can no longer tell your own body what to do. The hope of finding a solution to this has stimulated me for many years to unravel what goes wrong in the cells of Parkinson’s patients. This research is an important step forwards.”
Bart De Strooper (VIB/KU Leuven):
“Parkinson’s disease is one of the research focuses in our department. It gives great satisfaction that we have unraveled a molecular process responsible for the faulty energy production process in cells of Parkinson’s patients. This confirms our belief that repairing the energy production in cells is a possible therapeutic strategy.”
Faulty energy production forms the basis of Parkinson’s disease
Mitochondria are cell components that produce the energy required by a cell to function. The action of these mitochondria – and therefore the energy production in cells – is disrupted in Parkinson’s disease. The exact mechanism was unknown. In recent years, scientists have described various gene defects (mutations) in Parkinson’s patients that result in decreased activity of the mitochondria, including a mutation in the Pink1 gene.
Molecular mechanism provides ultimate proof
Vanessa Moraïs studied the link between Pink1, mitochondria and Parkinson’s disease in fruit-flies and mice with a defective Pink1 gene. These model organisms exhibited symptoms of Parkinson’s disease as a result of this defect. She was able to demonstrate that the defect in Pink1 resulted in the so-called ‘Complex I’ – a protein complex with a crucial role in the energy production of mitochondria – not being phosphorylated adequately, resulting in decreased energy production. When Moraïs and her colleagues ensured correct phosphorylation of Complex I, the Parkinson’s symptoms decreased or disappeared in mice and in patient-derived stem cell lines. The scientists thereby demonstrated that the lack of phosphorylation causes Parkinson’s disease in patients with a defect Pin1 gene.
Further research in Parkinson’s patients with defective Pink1 gene
This study reveals that repairing the phosphorylation of Complex I could be a treatment strategy for Parkinson’s disease. The VIB scientists have already used cells from Parkinson’s patients with a defective Pink1 gene to demonstrate that repairing the phosphorylation results in increased energy production. However, will this cause the symptoms of Parkinson’s disease to decrease or disappear? Only tests on patients can answer this question. According to the scientists, the best strategy would be to start with the sub-group of patients with a defective Pink1 gene. But before starting clinical trials, a lot of aspects still have to be tested.
Researchers ID more pesticides linked to Parkinson’s, gene that increases risk
Studies have shown that certain pesticides can increase people’s risk of developing Parkinson’s disease. Now, UCLA researchers have found that the strength of that risk depends on an individual’s genetic makeup, which, in the most pesticide-exposed populations, could increase a person’s chance of developing the debilitating disease two- to six-fold.
In an earlier study, published January 2013 in Proceedings of the National Academy of Sciences, the UCLA team discovered a link between Parkinson’s and the pesticide benomyl, a fungicide that has been banned by the U.S. Environmental Protection Agency. That study found that benomyl prevents the enzyme aldehyde dehydrogenase (ALDH) from converting aldehydes — organic compounds that are highly toxic to dopamine cells in the brain — into less toxic agents, thereby contributing to the risk of Parkinson’s.
For the current study, UCLA researchers tested a number of additional pesticides and found 11 that also inhibit ALDH and increase the risk of Parkinson’s — and at levels much lower than they are currently being used, said the study’s lead author, Jeff Bronstein, a professor of neurology and director of the movement disorders program at UCLA.
Bronstein said the team also found that people with a common genetic variant of the ALDH2 gene are particularly sensitive to the effects of ALDH-inhibiting pesticides and are two to six times more likely to develop Parkinson’s when exposed to these pesticides than those without the variant.
The results of the new epidemiological study appear Feb. 5 in the online issue of Neurology, the medical journal of the American Academy of Neurology.
"We were very surprised that so many pesticides inhibited ALDH and at quite low concentrations — concentrations that were way below what was needed for the pesticides to do their job," Bronstein said. "These pesticides are pretty ubiquitous and can be found on our food supply. They are used in parks and golf courses and in pest control inside buildings and homes. So this significantly broadens the number of people at risk."
The study compared 360 patients with Parkinson’s disease in three agriculture-heavy Central California counties and 816 people from the same area who did not have Parkinson’s. The researchers focused their analyses on individuals with ambient exposures to pesticides at work and at home, using information from the California Department of Pesticide Regulation.
In the previous PNAS study, Bronstein and his team had determined the mechanism that leads to increased risk. Exposure to pesticides starts a cascade of cellular events, preventing ALDH from keeping a lid on the aldehyde DOPAL, a toxin that naturally occurs in the brain. When ALDH does not detoxify DOPAL sufficiently, it accumulates, damages neurons and increases an individual’s risk of developing Parkinson’s.
"ALDH inhibition appears to be an important mechanism by which these environmental toxins contribute to Parkinson’s pathogenesis, especially in genetically vulnerable individuals," said study author Beate Ritz, a professor of epidemiology at UCLA’s Fielding School of Public Health. "This suggests several potential interventions to reduce Parkinson’s occurrence or to slow its progression."
In the current study, the research team developed a lab test to determine which pesticides inhibited ALDH. They then found that those participants in the epidemiologic study who had a genetic variant in the ALDH gene were at increased risk of Parkinson’s when exposed to these pesticides. Just having the variant alone, however, did not increase risk of the disease, Bronstein noted.
"This report provides evidence for the relevance of ALDH inhibition in Parkinson’s disease pathogenesis, identifies pesticides that should be avoided to reduce the risk of developing Parkinson’s disease and suggests that therapies modulating ALDH enzyme activity or otherwise eliminating toxic aldehydes should be developed and tested to potentially reduce Parkinson’s disease occurrence or slow its progression, particularly for patients exposed to pesticides," the study states.
(Source: newsroom.ucla.edu)
Scientists redefine how the brain plans movement
University of Queensland researchers have made a surprise discovery about how the brain plans movement that may lead to more targeted treatments for patients with Parkinson’s disease.
The discovery was made by UQ’s Queensland Brain Institute (QBI) researcher Professor Pankaj Sah in collaboration with neurologist Professor Peter Silburn and neurosurgeon Associate Professor Terry Coyne from the UQ Centre for Clinical Research.
Professor Sah said the team examined the brains of 10 patients with Parkinson’s disease while the patients were awake during deep brain stimulation surgery, and found more than one part of the brain is responsible for planning movement.
“This study aimed to improve understanding of how different parts of the brain are involved in planning movement and controlling gait,” Professor Sah said.
The team was particularly interested in a part of the brain stem known as the pedunculopontine nucleus (PPN), which lies in the deepest part of the brain.
The PPN has previously been targeted as a treatment point for people with advanced Parkinson’s disease who are unable to walk.
“To date, we have known that walking is generally controlled by the outer part of the brain known as the cortex,” Professor Sah said.
“When you decide to walk, the cortex sends signals to your brain stem which in turn signals the spinal cord to initiate movement.
“We have also known that neurons in the PPN are activated during limb movement, but our study has shown they were also activated when patients were simply thinking about walking.
“This is a complete surprise, because general thinking has been that movement planning takes place in the cortex, but this study indicates it might be happening in the brain stem as well.”
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, affecting more than six million people globally, and about 1 in 350 Australians.
Professor Sah said improved understanding of how the brain plans movement could lead to more targeted treatments for people with Parkinson’s.
“The cells involved in these networks seem to be one type of cell, so when thinking about drug treatments for Parkinson’s, maybe we should be targeting these cells,” Professor Sah said.
All the patients treated with deep brain stimulation also recorded positive outcomes with improvements with gait, highlighting the importance of neuroscientists working with clinicians.
Findings of the research are published in the Nature Neuroscience journal.
(Source: uq.edu.au)
Parkinson gene: Nerve growth factor halts mitochondrial degeneration
Neurodegenerative diseases like Parkinson’s disease involve the death of thousands of neurons in the brain. Nerve growth factors produced by the body, such as GDNF, promote the survival of the neurons; however, clinical tests with GDNF have not yielded in any clear improvements. Scientists from the Max Planck Institute of Neurobiology in Martinsried and their colleagues have now succeeded in demonstrating that GDNF and its receptor Ret also promote the survival of mitochondria, the power plants of the cell. By activating the Ret receptor, the scientists were able to prevent in flies and human cell cultures the degeneration of mitochondria, which is caused by a gene defect related to Parkinson’s disease. This important new link could lead to the development of more refined GDNF therapies in the future.
In his “Essay on the Shaking Palsy” of 1817, James Parkinson provided the first description of a disease that today affects almost 280,000 people in Germany. The most conspicuous symptom of Parkinson’s disease is a slow tremor, which is usually accompanied by an increasing lack of mobility and movement in the entire body. These symptoms are visible manifestations of a dramatic change that takes place in the brain: the death of large numbers of neurons in the Substantia nigra of the midbrain.
Despite almost 200 years of research into Parkinson’s, its causes have not yet been fully explained. It appears to be certain that, in addition to environmental factors, genetic mutations also play a role in the emergence of the disease. A series of genes is now associated with Parkinson’s disease. One of these is PINK1, whose mutation causes mitochondrial dysfunction. Mitochondria are a cell’s power plants and without them, a cell cannot function properly or regenerate. Scientists from the Max Planck Institute of Neurobiology and their colleagues from Munich and Martinsried have now discovered a hitherto unknown link that counteracts mitochondrial dysfunction in the case of a PINK1 mutation.
The PINK1 gene emerged at a very early stage in evolutionary history and exists in a similar form for example in humans, mice and flies. In the fruit fly Drosophila, a mitochondrial defect triggered by a PINK1 mutation manifests in the fraying of the muscles. Less visible, the flies’ neurons also die. The scientists studied the molecular processes involved in these changes and discovered that the activation of the Ret receptor counteracts the muscle degeneration. “This is a really interesting finding which links the mitochondrial degeneration in Parkinson’s disease with nerve growth factors,” reports Rüdiger Klein, the head of the research study. Ret is not an unknown factor for the Martinsried-based neurobiologists: “We already succeeded in demonstrating a few years ago in mice that neurons without the Ret receptor die prematurely and in greater numbers with increasing age,” says Klein.
The Ret receptor is the cells’ docking site for the growth factor GDNF, which is produced by the body. Various studies carried out in previous years showed that the binding of GDNF to its Ret receptor can prevent the early death of neurons in the Substantia nigra. However, clinical studies on the influence of GDNF on the progression of Parkinson’s in patients did not lead to any clear improvement in their condition.
The new findings from basic research suggest that the mitochondrial metabolism is boosted or re-established through Ret/GNDF. “Based on this finding, existing therapies could be refined or tailored to specific patient groups,” hopes Pontus Klein, who conducted the study within the framework of his doctoral thesis. This hope does not appear to be completely unfounded: The scientists have already discovered a Ret/GDNF effect in human cells with a PINK1 defect similar to that observed in the fruit fly. It may therefore be possible to search for metabolic defects in the mitochondria of Parkinson’s patients in future. A specially tailored GDNF therapy could then provide a new therapeutic approach for patients who test positively.
Long-term spinal cord stimulation stalls symptoms of Parkinson’s-like disease
Researchers at Duke Medicine have shown that continuing spinal cord stimulation appears to produce improvements in symptoms of Parkinson’s disease, and may protect critical neurons from injury or deterioration.
The study, performed in rats, is published online Jan. 23, 2014, in the journal Scientific Reports. It builds on earlier findings from the Duke team that stimulating the spinal cord with electrical signals temporarily eased symptoms of the neurological disorder in rodents.
"Finding novel treatments that address both the symptoms and progressive nature of Parkinson’s disease is a major priority," said the study’s senior author Miguel Nicolelis, M.D., Ph.D., professor of neurobiology at Duke University School of Medicine. "We need options that are safe, affordable, effective and can last a long time. Spinal cord stimulation has the potential to do this for people with Parkinson’s disease."
Parkinson’s disease is caused by the progressive loss of neurons that produce dopamine, an essential molecule in the brain, and affects movement, muscle control and balance.
L-dopa, the standard drug treatment for Parkinson’s disease, works by replacing dopamine. While L-dopa helps many people, it can cause side effects and lose its effectiveness over time. Deep brain stimulation, which emits electrical signals from an implant in the brain, has emerged as another valuable therapy, but less than 5 percent of those with Parkinson’s disease qualify for this treatment.
"Even though deep brain stimulation can be very successful, the number of patients who can take advantage of this therapy is small, in part because of the invasiveness of the procedure," Nicolelis said.
In 2009, Nicolelis and his colleagues reported in the journal Science that they developed a device for rodents that sends electrical stimulation to the dorsal column, a main sensory pathway in the spinal cord carrying information from the body to the brain. The device was attached to the surface of the spinal cord in rodents with depleted levels of dopamine, mimicking the biologic characteristics of someone with Parkinson’s disease. When the stimulation was turned on, the animals’ slow, stiff movements were replaced with the active behaviors of healthy mice and rats.
Because research on spinal cord stimulation in animals has been limited to the stimulation’s acute effects, in the current study, Nicolelis and his colleagues investigated the long-term effects of the treatment in rats with the Parkinson’s-like disease.
For six weeks, the researchers applied electrical stimulation to a particular location in the dorsal column of the rats’ spinal cords twice a week for 30-minute sessions. They observed a significant improvement in the rats’ symptoms, including improved motor skills and a reversal of severe weight loss.
In addition to the recovery in clinical symptoms, the stimulation was associated with better survival of neurons and a higher density of dopaminergic innervation in two brain regions controlling movement – the loss of which cause Parkinson’s disease in humans. The findings suggest that the treatment protects against the loss or damage of neurons.
Clinicians are currently using a similar application of dorsal column stimulation to manage certain chronic pain syndromes in humans. Electrodes implanted over the spinal cord are connected to a portable generator, which produces electrical signals that create a tingling sensation to relieve pain. Studies in a small number of humans worldwide have shown that dorsal column stimulation may also be effective in restoring motor function in people with Parkinson’s disease.
"This is still a limited number of cases, so studies like ours are important in examining the basic science behind the treatment and the potential mechanisms of why it is effective," Nicolelis said.
The researchers are continuing to investigate how spinal cord stimulation works, and are beginning to explore using the technology in other neurological motor disorders.