Posts tagged parkinson's disease
Articles and news from the latest research reports.
Deep Brain Stimulation Improves Non Motor Symptoms in Parkinson’s Disease as well as Motor Symptoms
Deep brain stimulation (DBS) has become a well-recognized non-pharmacologic treatment that improves motor symptoms of patients with early and advanced Parkinson’s disease. Evidence now indicates that DBS can decrease the number and severity of non motor symptoms of patients with Parkinson’s disease (PD) as well, according to a review published in the Journal of Parkinson’s Disease.
“Non motor features are common in PD patients, occur across all disease stages, and while well described, are still under-recognized when considering their huge impact on patients’ quality of life,” says Lisa Klingelhoefer, MD, a fellow at the National Parkinson Foundation International Centre of Excellence, Department of Neurology, King’s College Hospital and King’s College, London.
For example, DBS of the subthalamic nucleus (STN) is effective for alleviating sleep problems and fatigue associated with PD, producing noticeable long-term improvements in sleep efficiency and the quality and duration of continuous sleep. DBS also decreases nighttime and early morning dystonia and improves nighttime mobility. “DBS can contribute to better sleep, less daytime somnolence, improved mobility, and less need for dopamine replacement therapy,” says Dr. Klingelhoefer.
The effects of DBS on some other non motor symptoms of PD are less clear cut and transient worsening of neuropsychological and psychiatric symptoms have been reported. For instance, behavioral disorders such as impulsivity (e.g. hypersexuality, pathological gambling, and excessive eating) can occur or worsen in PD patients after STN DBS. While pre-existing drug-induced psychotic symptoms like hallucinations often disappear after STN DBS, transient psychotic symptoms such as delirium may emerge in the immediate post-operative period. Similarly, conflicting reports have found that STN DBS improves, worsens, or does not change mood disorders such as depression, mania, or anxiety.
“Further work is required in order to fully understand the mechanisms and impact of DBS of the STN or other brain structures on the non motor symptoms of PD,” concludes Dr. Klingelhoefer. She suggests that in the future, non motor symptoms of PD may become an additional primary indication for DBS.
PD is the second most common neurodegenerative disorder in the United States, affecting approximately one million Americans and five million people worldwide. Its prevalence is projected to double by 2030. The most characteristic symptoms are movement-related, such as involuntary shaking and muscle stiffness. Non motor symptoms, such as worsening depression, anxiety, olfactory dysfunction, sweating, bladder and bowel dysfunction, and sleep disturbances, can appear prior to the onset of motor symptoms.
Boost for dopamine packaging protects brain in Parkinson’s model
Researchers from Emory’s Rollins School of Public Health discovered that an increase in the protein that helps store dopamine, a critical brain chemical, led to enhanced dopamine neurotransmission and protection from a Parkinson’s disease-related neurotoxin in mice.
Dopamine and related neurotransmitters are stored in small storage packages called vesicles by the vesicular monoamine transporter (VMAT2). When released from these packages dopamine can help regulate movement, pleasure and emotional response. Low dopamine levels are associated with neurodegenerative diseases such as Parkinson’s disease and recent research has shown that VMAT2 function is impaired in people with the disease.
Lead researcher Gary W. Miller, PhD professor and associate dean for research at the Rollins School of Public Health and his team generated transgenic mice with increased levels of VMAT2 and found it led to an increase in dopamine release. In addition, the group found improved outcomes on anxiety and depressive behaviors, increased movement, and protection from MPTP, the chemical that can cause Parkinson’s disease-related damage in the brain.
The complete study is available in the June 17, 2014 edition of Proceedings of the National Academy of Sciences (PNAS).
According to Miller, “This work suggests that enhanced vesicular filling can be sustained over time and may be a viable therapeutic approach for a variety of central nervous system disorders that involve the storage and release of dopamine, serotonin or norepinephrine.”
(Source: news.emory.edu)
Hunting down the trigger for Parkinson’s: failing dopamine pump damages brain cells
A study group at the Medical University of Vienna’s Centre for Brain Research has investigated the function of an intracellular dopamine pump in Parkinson’s patients compared to a healthy test group. It turned out that this pump is less effective at pumping out dopamine and storing it in the brain cells of Parkinson’s sufferers. If dopamine is not stored correctly, however, it can cause self-destruction of the affected nerve cells.
In the brain, dopamine mediates the exchange of information between different neurons and, to help it do this, it is continuously reformed at the contact points between the corresponding nerve cells. It is stored in structures known as vesicles (intracellular bubbles) and it is released when required. In people with Parkinson’s disease, the death of these nerve cells causes a lack of dopamine, and this in turn causes the familiar movement problems such as motor retardation, stiffness of the muscles and tremors.
More than 50 years ago, in the Institute of Pharmacology at the University of Vienna (now the MedUni Vienna), Herbert Ehringer and Oleh Hornykiewicz discovered that Parkinson’s disease is caused by a lack of dopamine in certain regions of the brain. This discovery enabled Hornykiewicz to introduce the amino acid L-DOPA into the treatment of Parkinson’s to substitute the dopamine and make the symptoms of the condition manageable for years.
The reasons for the death of nerve cells in Parkinson’s disease are not yet fully understood, however, which is why it is still not possible to prevent the disease from developing. Nevertheless, dopamine itself, if it is not stored correctly in vesicles, can cause self-destruction of the affected nerve cells.
Now, a further step forward has been taken in the research into the causes of this disease: a study at the MedUni Vienna’s Centre for Brain Research, led by Christian Pifl and the now 87-year-old Oleh Hornykiewicz, compared the brains of deceased Parkinson’s patients with those of a neurologically healthy control group. For the first time, it was possible to prepare the dopamine-storing vesicles from the brains so that their ability to store dopamine by pumping it in could be measured in quantitative terms.
It turned out that the pumps in the vesicles of Parkinson’s sufferers pumped the dopamine out less efficiently. “This pump deficiency and the associated reduction in dopamine storage capacity of the Parkinson’s vesicles could lead to dopamine collecting in the nerve cells, developing its toxic effect and destroying the nerve cells,” explains Christian Pifl.
(Source: meduniwien.ac.at)
Study Describes New Models for Testing Parkinson’s Disease Immune-based Drugs
Using powerful, newly developed cell culture and mouse models of sporadic Parkinson’s disease (PD), a team of researchers from the Perelman School of Medicine at the University of Pennsylvania, has demonstrated that immunotherapy with specifically targeted antibodies may block the development and spread of PD pathology in the brain. By intercepting the distorted and misfolded alpha-synuclein (α-syn) proteins that enter and propagate in neurons, creating aggregates, the researchers prevented the development of pathology and also reversed some of the effects of already-existing disease. The α-syn clumps, called Lewy bodies, eventually kill affected neurons, which leads to clinical PD. Their work appears this week in Cell Reports.
Earlier studies by senior author Virginia M.Y. Lee, PhD, and her colleagues at Penn’s Center for Neurodegenerative Disease Research (CNDR) had demonstrated a novel pathology of PD in which misfolded α-syn fibrils initiate and propagate Lewy bodies via cell-to-cell transmission. This was accomplished using synthetically created α-syn fibrils that allowed them to observe how Parkinson’s pathology developed and spread in a mouse and in neurons in a dish. The present study is a proof-of-concept of how these models might be used to develop new PD therapies.
"Once we created these models, the first thing that came to mind is immunotherapy," says Lee, CNDR director and professor of Pathology and Laboratory Medicine. "If you can develop antibodies that would stop the spreading, you may have a way to at least retard the progression of PD." The current work, she explains, uses antibodies that were generated and characterized at CNDR previously to see if they would reduce the pathology both in cell culture and in animal models.
Lee’s team focused on anti-α-syn monoclonal antibodies (MAbs). “In animal models,” Lee explains, “the question we want to ask is, can we reduce the pathology and also rescue cell loss to improve the behavioral deficits?”
Using their previously established sporadic PD mouse model, the researchers conducted both prevention and intervention preclinical studies. For prevention studies, they injected mouse α-syn synthetic preformed fibrils into wild-type, normal mice, as a control, and then immediately treated the mice with Syn303, one of the MAbs used (or IgG, another type of common antibody, for the control mice).
The control group without MAb administration showed PD pathology in multiple brain areas over time, while the mice treated with Syn303 showed significantly reduced pathology in the same areas. For intervention studies, they treated PD mice with Syn303 several days after fibril injections when Lewy bodies were already present. They found that the progression of pathology was markedly reduced in the Syn303-treated mice versus mice that did not receive Syn303.
"But there are some limitations to experiments in live mice since it is difficult to directly study the mechanism of how it works," Lee says. "To do that, we went back to the cell culture model to ask whether or not the antibody basically prevents the uptake of misfolded α-syn." The cell culture experiments showed that MAbs prevented the uptake of misfolded α-syn fibrils by neurons and sharply reduced the recruitment of natural α-syn into new Lewy body aggregates.
Next steps for the team will be to refine the immunotherapeutic approach. “We need to make better antibodies that have high affinity for pathology and not the normal protein,” says Lee.
The team’s models also open up new opportunities for studying and treating PD. “The system really allows us to identify new targets for treating PD,” Lee says. “The cell model could be a platform to look for small molecular drugs that would inhibit pathology.” Their approach could also serve as a foundation for genetically based studies to identify specific genes involved in PD pathology.
“Hopefully more people will use the model to look for new targets or screen for treatments for PD. That would be terrific,” concludes Lee.
MRI brain scans detect people with early Parkinson’s
The new MRI approach can detect people who have early-stage Parkinson’s disease with 85% accuracy, according to research published in Neurology, the medical journal of the American Academy of Neurology.
'At the moment we have no way to predict who is at risk of Parkinson's disease in the vast majority of cases,' says Dr Clare Mackay of the Department of Psychiatry at Oxford University, one of the joint lead researchers. 'We are excited that this MRI technique might prove to be a good marker for the earliest signs of Parkinson's. The results are very promising.'
Claire Bale, research communications manager at Parkinson’s UK, which funded the work, explains: ‘This new research takes us one step closer to diagnosing Parkinson’s at a much earlier stage – one of the biggest challenges facing research into the condition. By using a new, simple scanning technique the team at Oxford University have been able to study levels of activity in the brain which may suggest that Parkinson’s is present. One person every hour is diagnosed with Parkinson’s in the UK, and we hope that the researchers are able to continue to refine their test so that it can one day be part of clinical practice.’
Parkinson’s disease is characterised by tremor, slow movement, and stiff and inflexible muscles. It’s thought to affect around 1 in 500 people, meaning there are an estimated 127,000 people in the UK with the condition. There is currently no cure for the disease, although there are treatments that can reduce symptoms and maintain quality of life for as long as possible.
Parkinson’s disease is caused by the progressive loss of a particular set of nerve cells in the brain, but this damage to nerve cells will have been going on for a long time before symptoms become apparent.
If treatments are to be developed that can slow or halt the progression of the disease before it affects people significantly, the researchers say, we need methods to be able to identify people at risk before symptoms take hold.
Conventional MRI cannot detect early signs of Parkinson’s, so the Oxford researchers used an MRI technique, called resting-state fMRI, in which people are simply required to stay still in the scanner. They used the MRI data to look at the ‘connectivity’, or strength of brain networks, in the basal ganglia – part of the brain known to be involved in Parkinson’s disease.
The team compared 19 people with early-stage Parkinson’s disease while not on medication with 19 healthy people, matched for age and gender. They found that the Parkinson’s patients had much lower connectivity in the basal ganglia.
The researchers were able to define a cut-off or threshold level of connectivity. Falling below this level was able to predict who had Parkinson’s disease with 100% sensitivity (it picked up everyone with Parkinson’s) and 89.5% specificity (it picked up few people without Parkinson’s – there were few false positives).
Dr Mackay explains: ‘Our MRI approach showed a very strong difference in connectivity between those who had Parkinson’s disease and those that did not. So much so, that we wondered if it was too good to be true and carried out a validation test in a second group of patients. We got a similar result the second time.’
The scientists applied their MRI test to a second group of 13 early-stage Parkinson’s patients as a validation of the approach. They correctly identified 11 out of the 13 patients (85% accuracy).
'We think that our MRI test will be relevant for diagnosis of Parkinson's,' says joint lead researcher Dr Michele Hu of the Nuffield Department of Clinical Neurosciences at Oxford University and the Oxford University Hospitals NHS Trust. 'We tested it in people with early-stage Parkinson's. But because it is so sensitive in these patients, we hope it will be able to predict who is at risk of disease before any symptoms have developed. However, this is something that we still have to show in further research.'
To see if this is the case, the Oxford University researchers are now carrying out further studies of their MRI technique with people who are at increased risk of Parkinson’s.
Researchers See Promise in Transplanted Fetal Stem Cells for Parkinson’s
Researchers at Harvard-affiliated McLean Hospital have found that fetal dopamine cells transplanted into the brains of patients with Parkinson’s disease were able to remain healthy and functional for up to 14 years, a finding that could lead to new and better therapies for the illness.
The discovery, reported in the June 5, 2014 issue of the journal Cell Reports, could pave the way for researchers to begin transplanting dopamine neurons taken from stem cells grown in laboratories, a way to get treatments to many more patients in an easier fashion.
"We have shown in this paper that the transplanted cells connect and live well and do all the required functions of nerve cells for a very long time," said Ole Isacson, MD (DR MED SCI), director of the Neuroregeneration Research Institute at McLean and a professor of neurology and neuroscience at Harvard Medical School.
The researchers looked at the brains of five patients who got fetal cell transplants over a period of 14 years and found that their dopamine transporters (DAT), proteins that pump the neurotransmitter dopamine, and mitochondria, the power plants of cells, were still healthy at the time the patients died, in each case of causes other than Parkinson’s.
The fact that these cells had remained healthy indicated that the transplants had been successful and that the transplanted cells had not been corrupted as some researchers had suggested they likely had been in other studies, said Dr. Isacson, lead author of the paper.
"These findings are critically important for the rational development of stem cell-based dopamine neuronal replacement therapies for Parkinson’s," the paper concluded.
So far, about 25 patients worldwide have been treated with this particular method of transplanting fetal dopamine cells over a period of two decades and most saw their symptoms improve markedly, he said.
Fetal cell transplants can reduce both Parkinson’s symptoms for many years and can reduce the need for dopamine replacement drugs, even though they can take months or years to start working, the paper said.
However, Dr. Isacson said proof had been lacking that the transplanted cells were able to remain healthy — until this study. This is important for research in the transplant field to move ahead, he said.
All of the patients were in the late stages of Parkinson’s disease at the time of their transplants. Parkinson’s is a disease characterized by tremors, rigidity, slowness of movement and poor balance. It is a chronic, progressive disease that results when dopamine-producing nerve cells in a part of the brain die or are impaired.
Dr. Isacson said there was a need to understand how transplanted neurons could survive despite ongoing disease process in the patients’ brains. He said there has been controversy among scientists, some of whom believe that the transplanted cells could be corrupted by toxic proteins associated with the disease process, even at the same time patients seemed to be doing better.
"Everything we saw looked very healthy," he said, referring to the dopamine transporters and mitochondria cells.
He said the method used to transplant the cells into these patients’ brains was different than another method used on about 60 other patients worldwide. In some of those other trials, scientists said the cells might have been damaged as a result of the disease process.
It may have been that the method used on the patients in this study, which injected tiny bits of liquefied dopamine nerve cells into the brain via a thin needle, was superior to the method used in other studies, which transplanted larger chunks of nerve cells using a larger needle, he said. The transplants on the patients in this study were done in Canada.
In this study, the researchers led by Dr. Isacson compared the patients’ own dopamine producing cells with the transplanted ones. “We found very different patterns,” he said.
The difference was seen in the DAT and mitochondria, which were unhealthy around the patients’ own dopamine neurons and healthy around the transplanted ones. “The transplanted cells don’t have the disease,” he said.
"This is very important in the quest for new therapies," he added.
It is very difficult to obtain dopamine nerve cells from fetal tissue, he said. It would be far easier to grow the cells in a laboratory from stem cells, he noted. There have been no stem cell transplants as of yet for Parkinson’s patients.
Researchers identify new gene involved in Parkinson’s disease
A team of UCLA researchers has identified a new gene involved in Parkinson’s disease, a finding that may one day provide a target for a new drug to prevent and potentially even cure the debilitating neurological disorder.
Parkinson’s disease is the second most common neurodegenerative disorder after Alzheimer’s disease, and there is no cure for the progressive and devastating illness. About 60,000 Americans are diagnosed with Parkinson’s disease each year. It is estimated that as many as 1 million Americans live with Parkinson’s disease, which is more than the number of people diagnosed with multiple sclerosis, muscular dystrophy and Lou Gehrig’s disease combined.
In Parkinson’s disease, multiple neurons in the brain gradually break down or die. This leads to the movement impairments, such as tremor, rigidity, slowness in movement and difficulty walking, as well as depression, anxiety, sleeping difficulties and dementia, said Dr. Ming Guo, the study team leader, associate professor of neurology and pharmacology and a practicing neurologist at UCLA.
A handful of genes have been identified in inherited cases of Parkinson’s disease. Guo’s team was one of two groups worldwide that first reported in 2006 in the journal Nature that two of these genes, PTEN-induced putative kinase 1 (PINK1) and PARKIN, act together to maintain the health of mitochondria – the power house of the cell that is important in maintaining brain health. Mutations in these genes lead to early-onset Parkinson’s disease.
Guo’s team has further shown that when PINK1 and PARKIN are operating correctly, they help maintain the regular shape of healthy mitochondria and promote elimination of damaged mitochondria. Accumulation of unhealthy or damaged mitochondria in neurons and muscles ultimately results in Parkinson’s disease.
In this study, the team found that the new gene, called MUL1 (also known as MULAN and MAPL), plays an important role in mediating the pathology of the PINK1 and PARKIN. The study, performed in fruit flies and mice, showed that providing an extra amount of MUL1 ameliorates the mitochondrial damage due to mutated PINK/PARKIN, while inhibiting MUL1 in mutant PINK1/PARKIN exacerbates the damage to the mitochondria. In addition, Guo and her collaborators found that removing MUL1 from mouse neurons of the PARKIN disease model results in unhealthy mitochondria and degeneration of the neurons.
The five-year study appears June 4, 2014, in eLife, a new, open access scientific journal for groundbreaking biomedical and life research sponsored by the Howard Hughes Medical Institute (United States), the Wellcome Trust (United Kingdom) and Max Plank Institutes (Germany).
"We are very excited about this finding," Guo said. "There are several implications to this work, including that MUL1 appears to be a very promising drug target and that it may constitute a new pathway regulating the quality of mitochondria."
Guo characterized the work as “a major advancement in Parkinson’s disease research.”
"We show that MUL1 dosage is key and optimizing its function is crucial for brain health and to ward off Parkinson’s disease," she said. "Our work proves that mitochondrial health is of central importance to keep us from suffering from neurodegeneration. Further, finding a drug that can enhance MUL1 function would be of great benefit to patients with Parkinson’s disease."
Going forward, Guo and her team will test these results in more complex organisms, hoping to uncover additional functions and mechanisms of MUL1. Additionally, the team will perform small molecule screens to help identify potential compounds that specifically target MUL1. Further, they will examine if mutations in MUL1 exist in some patients with inherited forms of Parkinson’s.
(Source: eurekalert.org)
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.
New treatment targeting versatile protein may protect brain cells in Parkinson’s disease
In Parkinson’s disease (PD), dopamine-producing nerve cells that control our movements waste away. Current treatments for PD therefore aim at restoring dopamine contents in the brain. In a new study from Lund University, researchers are attacking the problem from a different angle, through early activation of a protein that improves the brain’s capacity to cope with a host of harmful processes. Stimulating the protein, called Sigma-1 receptor, sets off a battery of defence mechanisms and restores lost motor function. The results were obtained in mice, but clinical trials in patients may not be far away.
By activating the Sigma-1 receptor, a versatile protein involved in many cellular functions, levels of several molecules that help nerve cells build new connections increased, inflammation decreased, while dopamine levels also rose. The results, published in the journal Brain, show a marked improvement of motor symptoms in mice with a Parkinson-like condition that had been treated with a Sigma-1-stimulating drug for 5 weeks.
This treatment has never before been studied in connection with Parkinson’s disease. However, various publications linked to stroke and motor neurone disease have reported positive results with drugs that stimulate the Sigma-1 receptor, and a biotech company in the US will soon begin clinical trials on Alzheimer’s patients. The fact that substances stimulating this protein are already available for clinical use is a major advantage, according to Professor M. Angela Cenci Nilsson, head of the research team at Lund University.
“It is a huge advantage that these substances have already been tested in people and approved for clinical application. It means that we already know that the body tolerates this treatment. Clinical trials for Parkinson’s disease could theoretically start any time”.
Boosting the brain’s in-built defence mechanisms with approaches like this is a rather new idea in Parkinson’s research. Professor Cenci Nilsson, however, believes that the number of targets for future treatments is increasing as we learn more and more about the complex effects of PD on many different types of cells in the brain.
“The motor improvements we have seen in mice are disproportionately large compared to the recovery of dopamine levels. We believe this is because the treatment has protected the brain against a series of indirect consequences triggered by the Parkinson-like lesion. For example, we know today that a loss of dopamine causes the target neurons to lose synapses, and also alters both neural pathways and non-neuronal cells in the brain. Since the Sigma-1 receptor is widely expressed in many cell types, the treatment could intervene in many of these damaging processes “.
The treatment was shown to be significantly more effective when started at the beginning of the most aggressive phase of dopamine cell death. As a future potential therapy for Parkinson’s disease, this treatment would therefore need to be started as soon as possible after diagnosis in order to deliver maximum impact.
“In order to accelerate a possible clinical translation of our findings, we will now seek further evidence in support of this type of treatment. We are now discussing various opportunities with different collaborating partners, and we will try to procure funding for clinical studies in Parkinson´s disease as soon as possible”, concludes M. Angela Cenci Nilsson.
(Source: lunduniversity.lu.se)
Visual clue to new Parkinson’s Disease therapies
Dr Chris Elliott, of the Department of Biology, and Dr Alex Wade, of the Department of Psychology, have devised a technique that could both provide an early warning of the disease and result in therapies to mitigate its symptoms.
In research reported in Human Molecular Genetics, they created a more sensitive test which detected neurological changes before degeneration of the nervous system became apparent.
In laboratory tests using fruit flies, the researchers discovered that a human genetic mutation that causes Parkinson’s amplified visual signals in young flies dramatically. This resulted in loss of vision in later life.
Working with researchers from the Danish pharmaceutical company, H.Lundbeck A/S, they tested a new drug that targets the Parkinson’s mutation in flies. This drug prevented the abnormal changes in the flies’ visual function.
It is the first time that the compound has been used in vivo and its effectiveness was analysed using the new, sensitive technique devised by Dr Wade. This was originally used for measuring vision in people with eye disease and epilepsy.
Dr Elliott, who is part-funded by Parkinson’s UK, said: “If this kind of drug proves to be successful in clinical trials, it would have the potential to bring long-lasting relief from PD symptoms and fewer side effects than existing levadopa therapy.”
Dr Wade added: “This technique forms a remarkable bridge between human clinical science and animal research. If it proves successful in the future, it could open the door to a new way of studying a whole range of neurological diseases.”
Senior Vice President, Research at Lundbeck, Kim Andersen, said: “This new research may prove to be groundbreaking in the understanding and treatment of Parkinson’s disease. Science does not currently have answers for what happens in the brain before and during the disease, but these discoveries may bring us closer to this understanding. This may also give us the opportunity to revolutionize the diagnosis and treatment of Parkinson’s disease, for the benefit of patients and their families.”
(Source: york.ac.uk)