Tag Archives: Parkinson’s Disease

A new study finds that a component of aspirin binds to an enzyme called GAPDH, which is believed to play a major role in neurodegenerative diseases, including Alzheimer’s, Parkinson’s and Huntington’s diseases.

Researchers discovered that salicylic acid, the primary breakdown product of aspirin, binds to GAPDH, thereby stopping it from moving into a cell’s nucleus, where it can trigger the cell’s death. The study, which appears in the journal PLOS ONE, also suggests that derivatives of salicylic acid may hold promise for treating multiple neurodegenerative diseases.

The researchers performed high-throughput screens to identify proteins in the human body that bind to salicylic acid. GAPDH, (Glyceraldehyde 3-Phosphate Dehydrogenase), is a central enzyme in glucose metabolism, but plays additional roles in the cell. Under oxidative stress—an excess of free radicals and other reactive compounds—GAPDH is modified and then enters the nucleus of neurons, where it enhances protein turnover, leading to cell death.

The anti-Parkinson’s drug deprenyl blocks GAPDH’s entry into the nucleus and the resulting cell death. The researchers discovered that salicylic acid also is effective at stopping GAPDH from moving into the nucleus and preventing cell death.

“The enzyme GAPDH, long thought to function solely in glucose metabolism, is now known to participate in intracellular signaling,” said co-author Solomon Snyder, professor of neuroscience at Johns Hopkins University in Baltimore. “The new study establishes that GAPDH is a target for salicylate drugs related to aspirin, and hence may be relevant to the therapeutic actions of such drugs.”

Source: Boyce Thompson Institute

New research could lead to improved methods of detection for early-onset Parkinson’s disease (PD).

Recording the responses of fruit flies (Drosophila melanogaster) to different visual patterns, using methods adapted from the study of vision in humans, scientists investigated the nervous systems of flies with different types of Parkinson’s mutations.

The researchers compared flies carrying mutations associated with early-onset Parkinson’s with ‘normal’ control flies and found increased neuronal activity to stimulation in the former group in ‘young’ flies.

By mapping the visual responses of fruit flies with different Parkinson’s genes, the scientists built a substantial data bank of results. Using this they were able to classify unknown flies as having a Parkinson’s-related mutation with 85 per cent accuracy.

Researchers believe it may be possible to transfer this method back to the clinic where early changes in vision may provide a ‘biomarker’ allowing screening for Parkinson’s before the onset of traditional motor-symptoms. Therefore, profiling human visual responses could prove an accurate and reliable test in diagnosing people with early-onset PD.

This method is also likely to succeed when transferred to human detection of Parkinson’s, as visual profiling in humans has proved accurate in the past in detecting genetic markers. In this study, as more complex light stimulations have been used, a more accurate picture of detecting a wider variety of different genetic markers has been revealed.

Source: University of York

JPND Board Member Dr. John Hardy of the UCL Institute of Neurology was awarded the $3 million Breakthrough Prize in Life Sciences for his pioneering research into the genetic causes of Alzheimer’s disease, other forms of dementia and Parkinson’s disease.

The Breakthrough Prize in Life Sciences honours ‘transformative advances toward understanding living systems and extending human life’. This is the first time that the prize has been awarded to a UK researcher.

Using innovative genetic analysis methods, Professor Hardy has made major contributions to the study of almost all major neurodegenerative diseases. He has published over 850 scientific papers, many of which are focused on neurological disorders and more specifically the genetics of Alzheimer’s disease. His research has underpinned nearly all basic science and treatment research into Alzheimer’s disease over the last 20 years.

“It is a great honour to be awarded the prize for our work dissecting the causes of Alzheimer and Parkinson’s diseases,” Hardy said. “It is, of course, our hope and aim that this understanding leads to effective treatments…I feel we can beat these diseases.”

Source: UCL

The EU Joint Programme – Neurodegenerative Disease Research (JPND) will shortly begin another action to support working groups on “Harmonisation and Alignment in Brain Imaging Methods for Neurodegeneration”.

The aim of the call is to establish a limited number of transnational, JPND-sponsored expert working groups to address issues of key relevance for the future use of brain imaging techniques in ND research. Each working group can bid up to €50,000 for support of its activities, which are expected to run for a maximum of 6 months.

This will be a 1-step call, anticipated to launch in early January 2016, with a likely submission deadline of March 2016. Further details will be provided on the call launch date in January 2016. However, any new ideas to tackle harmonisation and alignment in brain imaging will be welcome. For example, this may include:

Harmonisation of acquisition for current markers (acquisition and harmonisation of procedures, for example, for MR, FDG PET, and EEG signals)
Simplification of web access to image analysis environments (improving the secure access to innovative web-based image analysis environments for neurodegenerative diseases)
Innovative PET molecular markers (fostering the use of established and experimental PET methods)
Innovative ultra-high field (UHF) MR markers

Please Note:

Proposals are not limited to these topics, and may cover other topics within harmonisation and alignment of brain imaging methods.
All information regarding future JPND Call topics is subject to change.
Final call information will be published on the JPND website (www.jpnd.eu).

The diseases covered by JPND are:
– Alzheimer’s disease (AD) and other dementias
– Parkinson’s disease (PD) and PD‐related disorders
– Prion disease
– Motor neurone diseases (MND)
– Huntington’s Disease (HD)
– Spinocerebellar ataxia (SCA)
– Spinal muscular atrophy (SMA)

Scientists still do not know why some people develop Parkinson’s disease. Now researchers from Aarhus University and Aarhus University Hospital have taken an important step towards a better understanding of the disease. Their research indicates that Parkinson’s disease may begin in the gastrointestinal tract and spread through the vagus nerve to the brain.

“We have conducted a registry study of almost 15,000 patients who have had the vagus nerve in their stomach severed. Between approximately 1970-1995 this procedure was a very common method of ulcer treatment. If it really is correct that Parkinson’s starts in the gut and spreads through the vagus nerve, then these vagotomy patients should naturally be protected against developing Parkinson’s disease,” explains postdoc at Aarhus University Elisabeth Svensson on the hypothesis behind the study.

“Our study shows that patients who have had the the entire vagus nerve severed were protected against Parkinson’s disease. Their risk was halved after 20 years. However, patients who had only had a small part of the vagus nerve severed where not protected. This also fits the hypothesis that the disease process is strongly dependent on a fully or partially intact vagus nerve to be able to reach and affect the brain,” she says.

The research was recently published in the journal “Annals of Neurology”.

Source: Aarhaus University

Two recent studies have investigated the direct links and associations between depression and Parkinson’s Disease

A longitudinal study from Sweden investigated the long-term risk of Parkinson disease (PD) after depression and evaluated potential confounding by shared susceptibility to the two diagnoses.

Published in the journal Neurology, this study demonstrated a time-dependent effect, dose-response pattern for recurrent depression, and lack of evidence for co-aggregation among siblings which together indicate a direct association between depression and subsequent PD. Given that the association was significant for a follow-up period of more than two decades, depression may be a very early pro-dromal symptom of PD, or a causal risk factor.

The effects of anti-depressive treatments for Parkinson’s Disease were also recently reviewed in the journal Parkinsonism & Related Disorders. The associated meta-analysis in the study demonstrates that pharmacologic treatment with antidepressant medications, specifically the selective serotonin reuptake inhibitors (SSRIs), and behavioral interventions (CBT) significantly improved depression among Parkinson’s disease patients.

The authors examined trials assessing treatment for depression in Parkinson’s disease (dPD) and found that:

SSRIs demonstrate significant improvement in depressive symptoms.
Cognitive behavioral therapy (CBT) shows a substantial effect in dPD treatment.
Evidence of efficacy of both SSRIs and CBT is provided, at least on the short term.

Cohort Study: Depression and subsequent risk of Parkinson disease – A nationwide cohort study. Gustaffssonn et al., Neurology. Published online before print May 20, 2015, doi: 10.1212/WNL.0000000000001684

Antidepressive treatments for Parkinson’s disease: A systematic review and meta-analysis
Emily Bomasang-Layno, et al., Parkinsonism & Related Disorders, Available online 16 May 2015

Study demonstrates that free-water provides a potential non-invasive progression marker of the substantia nigra region in the brain.

Parkinson’s disease is a CNS disorder that results from the loss of cells in various parts of the brain, including a region called the substantia nigra. The substantia nigra cells produce dopamine, a chemical messenger responsible for transmitting signals within the brain that allow for coordination of movement.

With no objective test or biomarker for Parkinson’s, there is a clear need to develop non-invasive markers of substantia nigra progression in Parkinson’s disease. This study’s authors had previously found elevated free-water levels in the substantia nigra for patients with Parkinson’s disease compared with controls in single-site and multi-site cohorts.

In this study, published in the journal “Brain”, they tested the hypotheses that free-water levels in the substantia nigra of Parkinson’s disease increase following 1 year of progression, and that baseline free-water levels in the substantia nigra predict the change in bradykinesia following 1 year.
The researchers conducted a longitudinal study in controls (n = 19) and patients with Parkinson’s disease (n = 25). Diffusion imaging and clinical data were collected at baseline and after 1 year. Free-water analyses were performed on diffusion imaging data using blinded, hand-drawn regions of interest in the posterior substantia nigra.

The results found that free water levels increases with progression of Parkinson’s disease, and predicts subsequent changes in bradykinesia and cognitive status over 1 year, thus demonstrating that free-water provides a potential non-invasive progression marker of the substantia nigra.

Longitudinal changes in free-water within the substantia nigra of Parkinson’s disease
Edward Ofori ,et al., DOI: http://dx.doi.org/10.1093/brain/awv136

A small sensor, headphones and a mobile phone – the elements of a prototype kit that is giving hope of relief for sufferers of Parkinson’s disease.

A European Framework Programme-backed research project being spearheaded in Barcelona does not offer a cure for the degenerative condition, but it could improve the quality of life of patients and give them more autonomy.

The project is aimed at helping patients manage the different stages of their disease more autonomously. People participating in the study wear a sensor on their waist that records movement data and identifies symptoms. When the patient lacks coordination, acoustic stimuli in the ear help them walk in a straight line.

The data is also sent via mobile phone to doctors, who can follow the evolution and adapt treatment accordingly. “The device tells us how many hours the patient’s state is ‘on’ and ‘off’, how the patient walks during these two different stages of the disease,” says Àngels Bayés, a neurologist at the Teknon Medical Centre, leading the research. “We’re also able to know if the patient suffers from blockages or not, and if so how many blockages he suffers throughout the day. We can also know how fast he can walk. “When the system automatically detects that the patient has motor problems, it activates acoustic stimuli to help the patient walk better.”

Encouraging trials
Researchers say first trials have confirmed that the device can indeed help patients increase their autonomy, although Paola Quispe, a Teknon Medical Centre nurse, says patients she has worked with have suggested some minor improvements: “Most of the patients have said they would prefer smaller sensors. There’s also a gap of around one minute between the moment the sensors identify a problem and the sending of the acoustic stimulation. Patients also said they would prefer to have musical rhythms, instead of just the beat of a metronome.”

Now researchers are working on giving the device the capacity to regulate the medication the patients receive, in real-time and in response to their body’s needs, as Joan Cabestany, a telecommunications engineer and coordinator of the REMPARK project, as it is called, explains: “The next step is to transform this device into a fully operational medical aid. A device that will help doctors provide better diagnostics, and also, eventually, allow them to adapt the patients medication, which will improve their health. But medical devices are heavily regulated in Europe, so we need to work further in this direction.”

Source: EuroNews

Genetic risk for Parkinson’s disease (PD) may be due as much to multiple genes with small individual effects as to single high-risk genes, research suggests.

Nigel Williams (Cardiff University School of Medicine, UK) and colleagues used data from five PD genome-wide association studies, involving 5333 PD cases and 12,298 controls. The team tested 259,577 single nucleotide polymorphism (SNPs) in a subset of 1705 PD cases and 6200 controls from the UK, identifying between nine and 30,157 SNPs that were significantly enriched among the PD patients, depending on the significance threshold of association used.

Applying a polygenic score based on these SNPs to two subsets of patients from the USA and one from Germany revealed significant enrichment of the SNPs identified in the UK patients in these independent cohorts.

Patients lacking single high-risk genetic mutations who nevertheless develop the condition at a young age would be expected to have an increased polygenic risk, say the researchers. “Our study has identified compelling evidence that supports this hypothesis”, they write in the Annals of Neurology.

The authors caution that “the derived polygenic scores have little value for predicting an individual’s risk of developing PD”, but add that “measures of polygenic burden could prove useful in distinguishing PD patients whose disease liability is most likely to carry the largest or smallest genetic component.”

This would therefore facilitate efforts to identify environmental risk factors and gene–environment interactions.

Source; NewsMedical.net

Creatine monohydrate doesn’t appear to slow the progression of Parkinson’s disease, according to research published in the February 10 issue of the Journal of the American Medical Association (JAMA).

The new study included 1,741 people in the United States and Canada who had been diagnosed with Parkinson’s disease within the previous five years. All were receiving treatment for Parkinson’s disease. As part of the study, they were randomly assigned to take creatine monohydrate or a placebo in addition to their usual treatment.

The patients were enrolled from March 2007 to May 2010 and followed up until September 2013. The study was halted early because those taking creatine showed no differences in disease progression compared to those taking the placebo.

“These findings do not support the use of creatine monohydrate in patients with Parkinson’s disease,” study author Karl Kieburtz, MD, MPH, of the University of Rochester in New York, and colleagues write.

Source: eMPR