Posts tagged parkinson's disease

New Penn Medicine research shows that neuropsychiatric symptoms such as depression, anxiety and fatigue are more common in newly diagnosed Parkinson’s disease (PD) patients compared to the general population. The study also found that initiation of dopamine replacement therapy, the most common treatment for PD, was associated with increasing frequency of impulse control disorders and excessive daytime sleepiness. The new findings, the first longitudinal study to come out of the Parkinson’s Progression Markers Initiative (PPMI), are published in the August 15, 2014, issue of Neurology®, the medical journal of the American Academy of Neurology.

The PPMI, a landmark, multicenter observational clinical study sponsored by The Michael J. Fox Foundation for Parkinson’s Research, uses a combination of advanced imaging, biologics sampling and behavioral assessments to identify biomarkers of Parkinson’s disease progression. The Penn study, which represents neuropsychiatric and cognitive data from baseline through the first 24 months of follow up, was conducted in collaboration with the Philadelphia VA Medical Center and the University Hospital Donostia in Spain.

The study examined 423 newly diagnosed, untreated Parkinson’s patients and 196 healthy controls at baseline and 281 people with PD at six months. Of these, 261 PD patients and 145 healthy controls were evaluated at 12 months, and 96 PD patients and 83 healthy controls evaluated at 24 months.

PD patients were permitted to begin dopamine therapy at any point after their baseline evaluation.

“We hypothesized that neuropsychiatric symptoms would be common and stable in severity soon after diagnosis and that the initiation of dopamine replacement therapy would modify their natural progression in some way,” says senior author, Daniel Weintraub, MD, associate professor of Psychiatry and Neurology at the Perelman School of Medicine at the University of Pennsylvania and a fellow in Penn’s Institute on Aging.

The Penn team showed that while there was no significant difference between PD patients and healthy controls in the frequency of impulse control disorders, a neuropsychiatric symptom that can lead to compulsive gambling, sexual behavior, eating or spending, 21 percent of newly diagnosed PD patients screened positive for such symptoms at baseline. That percentage did not increase significantly over the 24-month period.

However, six patients who had been on dopamine therapy for more than a year at the 24-month evaluation showed impulse control disorders or related behavior symptoms while no impulse control incident symptoms were reported in PD patients who had not commenced dopamine therapy. Dopamine therapy did help with fatigue, with 33 percent of patients improving their fatigue test score over 24 months compared with only 11 percent of patients not on dopamine therapy.

The investigators also found evidence that depression may be undertreated in early PD patients: Two-thirds of patients who screened positive for depression at any time point were not taking an antidepressant.

PPMI follows volunteers for five years, so investigators plan to expand upon these results, which Weintraub still considers preliminary. “We will more closely look at cognitive changes over time,” he says. “Two years is not a sufficient period of follow up to really look at meaningful cognitive decline.”

The perspective of time is what makes the PPMI such an important initiative, Weintraub points out, since many patients with the disease live for 10 to 20 years following their diagnosis. “It’s really a chance to assess the frequency and characteristics of psychiatric and cognitive symptoms in PD, compare it with healthy controls, and then also look at its evolution over time,” he says. “The hope is that we will be able to continue this work so that we can obtain long-term follow up data on these patients,” says Weintraub.

(Source: uphs.upenn.edu)

Depression is known to be a common symptom of Parkinson’s disease, but remains untreated for many patients, according to a new study by Northwestern Medicine investigators in collaboration with the National Parkinson’s Foundation (NPF).

In fact, depression is the most prevalent non-motor symptom of Parkinson’s, a chronic neurodegenerative disorder typically associated with movement dysfunction.  

“We confirmed suspicion that depression is a very common symptom in Parkinson’s disease. Nearly a quarter of the people in the study reported symptoms consistent with depression,” said Danny Bega, MD, ’14 GME, instructor in the Ken and Ruth Davee Department of Neurology and first author of the study. “This is important because previous research has determined that depression is a major determinant of overall quality of life.”

Using the NPS’s patient database, the investigators looked at records of more than 7,000 people with Parkinson’s disease. Among those with high levels of depressive symptoms, only one-third had been prescribed antidepressants before the study began, and even fewer saw social workers or mental health professionals for counseling.

The investigators then focused their analysis on the remaining two-thirds of patients with depressive symptoms who were not receiving treatment at the start of the study. Throughout a year of observation, less than 10 percent of them received prescriptions for antidepressants or referrals to counseling. Physicians were most likely to identify depression and advocate treatment for patients with the severest depression scores.

The findings were published in the Journal of Parkinson’s Disease.

“The majority of these patients remained untreated,” said Dr. Bega. “Still, the physician recognition of depression in this population was actually better than previous reports had suggested.”

However, recognition may be lower for the general population of patients with Parkinson’s disease – the patients in this study visited medical centers deemed “Centers of Excellence” by the NPF.

“Physicians must be more vigilant about screening patients for depression as part of a routine assessment of Parkinson’s disease, and the effectiveness of different treatments for depression in this population need to be assessed,” said Dr. Bega.

(Source: feinberg.northwestern.edu)

Parkinson’s disease affects neurons in the Substantia nigra brain region – their mitochondrial activity ceases and the cells die. Researchers at the Max Planck Institute of Molecular Cell Biology and Genetics show that supplying D-lactate or glycolate, two products of the gene DJ-1, can stop and even counteract this process: Adding the substances to cultured HeLa cells and to cells of the nematode C. elegans restored the activity of mitochondria and prevented the degeneration of neurons. They also showed that the two substances rescued the toxic effects of the weed killer Paraquat. Cells that had been treated with this herbicide, which is known to cause a Parkinson’s like harm of mitochondria, recovered after the addition of the two substances. Both glycolic and D-lactic acids occur naturally in unripe fruits and certain kinds of yoghurt.

(Image caption: Inactivation of the DJ-1 gene results in mitochondrial dysfunction (left), which can be restored by glycolate or D-lactate (right). Active mitochondria are shown in red, DNA is shown in blue. Credit: © MPI-CBG)

Teymuras Kurzchalia and Tony Hyman both have labs at the Max Planck Institute of Molecular Cell Biology and Genetics with rather different research programs – but both happened to stumble upon the gene DJ-1 and joined forces. This gene, originally thought of as an oncogene, has been linked to Parkinson’s disease since 2003. Recent studies showed that DJ-1 belongs to a novel glyxolase family. The major function of these genes is assumed to detoxify aggressive aldehyde by-products from mitochondrial metabolism. The Dresden research team now showed that the products of DJ-1, D-lactate and glycolate, are actually required to maintain the high mitochondrial potential and thus can prevent the degeneration of neurons implicated in Parkinson’s disease.

Their experiments proved that both substances are lifesavers for neurons: Adding them to affected cells, in other words cells treated with the environmental poison Paraquat or with a down-regulated DJ-1, decreased the toxic effect of the herbicide, restored the activity of the mitochondria and thus ensured the survival of the neurons.

„We do not yet understand how exactly D-lactate and glycolate achieve this curative and preventive effect, but the next step will be to investigate the molecular mechanism underlying this process”, say Hyman and Kurzchalia. In addition to further molecular investigation, they also have more concrete plans for the future: As Kurzchalia says “we can develop a yoghurt enriched with D-lactate: It could serve as a protection against Parkinson’s and is actually very tasty at the same time!“ This is why the researchers have filed a patent for their finding.

Many diseases are associated with a decline in mitochondrial activity, not only Parkinson’s. Thus, the researchers believe that the DJ1-products could have a general role in protecting cells from decline.

(Source: mpg.de)

An experimental anti-inflammatory drug can protect vulnerable neurons and reduce motor deficits in a rat model of Parkinson’s disease, researchers at Emory University School of Medicine have shown.

The results were published Thursday, July 24 in the Journal of Parkinson’s Disease.

The findings demonstrate that the drug, called XPro1595, can reach the brain at sufficient levels and have beneficial effects when administered by subcutaneous injection, like an insulin shot. Previous studies of XPro1595 in animals tested more invasive modes of delivery, such as direct injection into the brain.

“This is an important step forward for anti-inflammatory therapies for Parkinson’s disease,” says Malu Tansey, PhD, associate professor of physiology at Emory University School of Medicine. “Our results provide a compelling rationale for moving toward a clinical trial in early Parkinson’s disease patients.”

The new research on subcutaneous administration of XPro1595 was funded by the Michael J. Fox Foundation for Parkinson’s Research (MJFF). XPro1595 is licensed by FPRT Bio, and is seeking funding for a clinical trial to test its efficacy in the early stages of Parkinson’s disease.

“We are proud to have supported this work and glad to see positive pre-clinical results,” said Marco Baptista, PhD, MJFF associate director of research programs. “A therapy that could slow Parkinson’s progression would be a game changer for the millions living with this disease, and this study is a step in that direction.”

In addition, Tansey and Yoland Smith, PhD, from Yerkes National Primate Research Center, were awarded a grant this week from the Parkinson’s Disease Foundation to test XPro1595 in a non-human primate model of Parkinson’s.

Evidence has been piling up that inflammation is an important mechanism driving the progression of Parkinson’s disease. XPro1595 targets tumor necrosis factor (TNF), a critical inflammatory signaling molecule, and is specific to the soluble form of TNF. This specificity would avoid compromising immunity to infections, a known side effect of existing anti-TNF drugs used to treat disorders such as rheumatoid arthritis.

“Inflammation is probably not the initiating event in Parkinson’s disease, but it is important for the neurodegeneration that follows,” Tansey says. “That’s why we believe that an anti-inflammatory agent, such as one that counteracts soluble TNF, could substantially slow the progression of the disease.”

Postdoctoral fellow Christopher Barnum, PhD and colleagues used a model of Parkinson’s disease in rats in which the neurotoxin 6-hydroxydopamine (6-OHDA) is injected into only one side of the brain. This reproduces some aspects of Parkinson’s disease: neurons that produce dopamine in the injected side of the brain die, leading to impaired movement on the opposite side of the body.

When XPro1595 is given to the animals 3 days after 6-OHDA injection, just 15 percent of the dopamine-producing neurons were lost five weeks later. That compares to controls in which 55 percent of the same neurons were lost. By reducing dopamine neuron loss with XPro1595, the researchers were also able to reduce motor impairment. In fact, the degree of dopamine cell loss was highly correlated both with the degree of motor impairment and immune cell activation.

When XPro1595 is given two weeks after injection, 44 percent of the vulnerable neurons are still lost, suggesting that there is a limited window of opportunity to intervene.

“Recent clinical studies indicates there is a four or five year window between diagnosis of Parkinson’s disease and the time when the maximum number of vulnerable neurons are lost,” Dr. Tansey says. “If this is true, and if inflammation is playing a key role during this window, then we might be able to slow or halt the progression of Parkinson’s with a treatment like XPro1595.”

(Source: news.emory.edu)

Investigators at The Feinstein Institute for Medical Research have utilized a new image-based strategy to identify and measure placebo effects in randomized clinical trials for brain disorders. The findings are published in the August issue of The Journal of Clinical Investigation.

Parkinson’s disease is the second most common neurodegenerative disease in the US. Those who suffer from Parkinson’s disease most often experience tremors, slowness of movement (bradykinesia), rigidity, and impaired balance and coordination. Patients may have difficulty walking, talking or completing simple daily tasks. They may also experience depression and difficulty sleeping due to the disease. The current standard for diagnosis of Parkinson’s disease relies on a skilled healthcare professional, usually an experienced neurologist, to determine through clinical examination that someone has it. There currently is no cure for Parkinson’s disease, but medications can improve symptoms.

A team of researchers at the Feinstein Institute’s Center for Neurosciences, led by David Eidelberg, MD, has developed a method to identify brain patterns that are abnormal or indicate disease using imaging techniques. To date, this approach has been used successfully to identify specific networks in the brain that indicate a patient has or is at risk for Parkinson’s disease and other neurodegenerative disorders.

"One of the major challenges in developing new treatments for neurodegenerative disorders such as Parkinson’s disease is that it is common for patients participating in clinical trials to experience a placebo or sham effect," noted Dr. Eidelberg. "When patients involved in a clinical trial commonly experience benefits from placebo, it’s difficult for researchers to identify if the treatment being studied is effective. In a new study conducted by my colleagues and myself, we have used a new image-based strategy to identify and measure placebo effects in brain disorder clinical trials."

In the current study, the researchers used their network mapping technique to identify specific brain circuits underlying the response to sham surgery in Parkinson’s disease patients participating in a gene therapy trial. The expression of this network measured under blinded conditions correlated with the sham subjects’ clinical outcome; the network changes were reversed when the subjects learned of their sham treatment status. Finally, an individual subject’s network expression value measured before the treatment predicted his/her subsequent blinded response to sham treatment. This suggests that this novel image-based measure of the sham-related network can help to reduce the number of subjects assigned to sham treatment in randomized clinical trials for brain disorders by excluding those subjects who are more likely to display placebo effects under blinded conditions.

(Source: eurekalert.org)

Up to 70% of Parkinson’s disease (PD) patients experience sleep problems that negatively impact their quality of life. Some patients have disturbed sleep/wake patterns such as difficulty falling asleep or staying asleep, while other patients may be subject to sudden and involuntary daytime sleep “attacks.” In the extreme, PD patients may exhibit REM-sleep behavior disorder (RBD), characterized by vivid, violent dreams or dream re-enactment, even before motor symptoms appear. A review in the Journal of Parkinson’s Disease discusses the underlying causes of sleep problems in PD, as well as medications, disease pathology, and comorbidities, and describes the most appropriate diagnostic tools and treatment options.

Sleep problems in PD patients can have wide-ranging adverse effects and can worsen in later stages of the disease. Sleepiness socially isolates patients and excessive sleepiness can put patients at risk of falls or injury, and can mean patients must give up driving. Sleepiness can impair cognition and concentration, exacerbate depression, and interfere with employment. Wakefulness at night impairs daytime wakefulness and may also cause mood instabilities and can exhaust caregivers.

“Diagnosis and effective treatment and management of these problems are essential for improving the quality of life and reducing institutionalization of these patients,” says lead author Wiebke Schrempf, MD, Technische Universität Dresden, Faculty of Medicine Carl Gustav Carus, Department of Neurology, Division of Neurodegenerative Diseases, Dresden, Germany.

Dr. Schrempf and colleagues describe some of the complexities associated with treating sleep problems in PD patients, such as the worsening of sleep problems by dopaminergic medications used to treat motor symptoms. Lower doses of levodopa or dopamine agonists are able to improve sleep quality partly by reducing motor symptoms such as nighttime hypokinesia (decreased body movement), dyskinesia (abnormal voluntary movements), or tremor (involuntary shaking), which interfere with normal sleep. However, the same medications may also cause excessive daytime sleepiness. The report describes how changing medication, dose, duration of treatment, or timing of administration can improve outcomes.

The presence of other conditions common in PD patients such as depression, dementia, hallucinations, and psychosis may interfere with sleep. Unfortunately, some antidepressants can also impair sleep.

Sleep problems may also be harbingers of future neurodegenerative disease. Patients with RBD exhibit intermittent loss of normal muscle relaxation during REM sleep and engage in dream enactment behavior during which they may shout, laugh, or exhibit movements like kicking and boxing. “RBD seems to be a good clinical predictor of emerging neurodegenerative diseases with a high specificity and low sensitivity, whereas other early clinical features of PD, such as olfactory dysfunction and constipation, are less specific,” says Dr. Schrempf. “These early clues may help identify PD patients before motor symptoms appear, when disease-modifying therapies may be most beneficial.”

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, cognition, and anxiety, olfactory dysfunction, and sleep disturbances, can appear prior to the onset of motor symptoms.

(Source: alphagalileo.org)