Tag: Parkinson's Disease

Categories : Neurodegenerative DiseasesTags :

Peptide Discovery Could Halt Nerve Degeneration

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A healthy neuron.
A healthy neuron. Credit: NIH

Promising results have been found in the quest for a treatment to halt nerve cell degeneration in disorders like Parkinson’s disease, by preventing their mitochondria from breaking apart with a particular peptide.

The research, published in Brain, examined how the long axons that carry messages between nerve cells in the brain can break down, which causes increasingly worse tightening of the leg muscles, leading to imbalance and eventually paralysis, in addition to other symptoms.

Animal studies have shown it may be a problem with the mitochondria that leads to the axons breaking down or not growing long enough. Since studying human nerve cells is difficult, the researchers made use of human stem cells they modified to become nerve cells with the genetic disorder for a particular type of hereditary spastic paraplegia.

“What we found was that the mitochondria in these cells were breaking apart, what we call mitochondrial fission, and that caused the axons to be shorter and less effective at carrying messages to the brain,” study leader Prof Xue-Jun Li said. “We then looked at whether a particular agent would change the way the nerve cells function — and it did. It inhibited the mitochondrial fission and let the nerve cells grow normally and also stopped further damage.”

What this means for the thousands of people affected by this type of genetic disorder is that this peptide could prove to be useful for a drug or other therapy to stop the nerve cells from becoming damaged or possibly even reverse the course of the damage. Additionally, gene therapy could also prevent mitochondrial damage, the researchers suggested, which would provide another strategy to reverse the nerve damage.

Source: University of Illinois Chicago

Categories : Neurodegenerative DiseasesTags :

Deaths from Parkinson’s on the Rise

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Photo by Kindel Media on Pexels

Over the last two decades, the death rate from Parkinson’s disease has risen about 63% in the US, and the death rate was twice as high in men as in women, with a higher death rate in White people than other racial/ethnic groups.

“We know that people are living longer and the general population is getting older, but that doesn’t fully explain the increase we saw in the death rate in people with Parkinson’s,” study author Wei Bao, MD, PhD, who conducted the research at the University of Iowa in Iowa City. “Understanding why more people are dying from this disease is critical if we are going to reverse the trend.”

The study, published in Neurology, looked at a national death registry that included 479 059 people who died of Parkinson’s from 1999–2019.

After adjusting for age, researchers found that the number of people who died from the disease increased from 5.4 per 100,000 people in 1999 to 8.8 per 100 000 people in 2019. The average annual increase was 2.4%.

Mortality increased significantly across all age groups, both sexes, various racial and ethnic groups and different urban-rural classifications. However, death rates were twice as high in men as in women. According to Dr Bao, a possible explanation for this sex difference is that oestrogen, which leads to higher dopamine levels in parts of the brain that control motor responses, may protect women from developing Parkinson’s.

White people were more likely to die from Parkinson’s than other racial and ethnic groups. In 2019, the death rate for White people was 9.7 per 100 000, followed by Hispanic people, at 6.5 per 100 000, and non-Hispanic Black people, at 4.7 per 100 000. In previous studies, compared to White people, Black and Hispanic people are less likely to see an outpatient neurologist, due to socioeconomic barriers, suggesting that White people may have a higher chance of receiving a Parkinson’s diagnosis.

“It’s important to continue to evaluate long-term trends in Parkinson’s death rates,” Dr Bao said. “This can inform future research that may help pinpoint why more people are dying of the disease. Also, updating vital statistics about Parkinson’s death rates may be used for priority setting and financing of health care and policy.”

A limitation of the study is that only one underlying cause of death was recorded on each death certificate, so only people who were recorded as having died of Parkinson’s were included in the study. This may not accurately reflect the prevalence of the disease as a cause of death.

Source: American Academy of Neurology

Categories : Neurodegenerative DiseasesTags :

Antioxidant Trial for Parkinson’s Disease Flops

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Source: Pixabay

Raising brain levels of the natural antioxidant urate through ionosine administration failed to slow the progression of Parkinson’s disease (PD), reported researchers at Massachusetts General Hospital (MGH).

Still, the rigor of the clinical study and some of its novel investigative approaches are seen as improving the prospects for future clinical trials to demonstrate the benefits of disease-modifying therapies for people with Parkinson’s disease. The results were published in JAMA.

“The convergence of epidemiological, biological, and clinical data from past research made a compelling argument that elevating urate, the main antioxidant circulating in the blood, could protect against the oxidative damage thought to play a role in Parkinson’s disease,” explained senior author Michael Schwarzschild, MD, PhD, a neurologist at MGH. “While our study did not rule out a protective effect of urate in Parkinson’s, it clearly showed that increasing urate did not slow disease progression based on clinical assessments and serial bran scan biomarkers of neurodegeneration.”

So far, no treatment has been shown to prevent or forestall progression of Parkinson’s disease, which affects the body’s motor system. The Phase III trial, SURE-PD3, enrolled 298 individuals recently diagnosed with early Parkinson’s disease based on MRI scans indicating loss of dopamine-producing brain cells characteristic of PD. In participants who received the metabolite inosine — which raises levels of urate in the brain and blood and has shown neuroprotective properties in preclinical models — there was no significant difference in the rate of disease progression compared to placebo. Additionally, there was an increased rate of kidney stones among those randomised to inosine treatment.

Despite the lack of evidence to support urate elevation, Dr Schwarzschild found the study successful in other ways. “The findings were very helpful in providing a reality check that now allows the field to move on to other therapeutic approaches,” he explained. “We also learned a lot in terms of clinical trials science for Parkinson’s, and ways to conduct future studies that will increase their chance of success.” One of those ways is to tailor treatment to subsets of patients who are most likely to benefit – a hallmark of the move to precision medicine in Parkinson’s research. In SURE-PD3, for example, only patients who had lower levels of urate were enrolled to increase the chance of benefit and reduce the chance of side effects.

Another innovative feature of the trial is that many participants gave blood samples for genotyping – a valuable source of genetic information that could figure in the hunt for clinical solutions in smaller subpopulations of PD patients. A significant number also volunteered for an extension of the study to help determine how monitoring at home could provide more efficient ways to conduct future clinical trials. “There were many positive results from SURE-PD3 which we believe will improve the prospects of researchers discovering a disease-modifying therapy which people with Parkinson’s have been desperately seeking,” Dr Schwarzschild concluded.

Source: Massachusetts General Hospital

Categories : Medical Research & Technology Neurodegenerative DiseasesTags :

Precise Ultrasound Heating of Neurons Could Treat Neurological Disorders

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Image source: Fakurian Design on Unsplash

A multidisciplinary team at Washington University in St. Louis has developed a new brain stimulation technique using focused ultrasound that is able to turn specific types of neurons in the brain on and off and precisely control motor activity without surgical device implantation.

Being able to turn neurons on and off can treat certain neurological disorders such as Parkinson’s disease and epilepsy. Used for over six decades, deep brain stimulation techniques have had some treatment success in neurological disorders, but those require surgical device implantation. 

The team, led by Hong Chen, assistant professor of biomedical engineering in the McKelvey School of Engineering and of radiation oncology at the School of Medicine, is the first to provide direct evidence showing noninvasive activation of specific neuron types in mammalian brains by combining an ultrasound-induced heating effect and genetics, which they have named sonothermogenetics. It is also the first work to show that the ultrasound- genetics combination can robustly control behaviour by stimulating a specific target deep in the brain.

The results of the three years of research were published online in Brain Stimulation. 

“Our work provided evidence that sonothermogenetics evokes behavioural responses in freely moving mice while targeting a deep brain site,” Chen said. “Sonothermogenetics has the potential to transform our approaches for neuroscience research and uncover new methods to understand and treat human brain disorders.”

Chen and colleagues delivered a viral construct containing TRPV1 ion channels to genetically-selected neurons in a mouse model. Then, they delivered small pulses of heat generated by low-intensity focused ultrasound to the selected neurons in the brain via a wearable device. The heat, only a few degrees warmer than body temperature, activated the TRPV1 ion channel, which then acted as a switch to turn the neurons on or off.

“We can move the ultrasound device worn on the head of free-moving mice around to target different locations in the whole brain,” said Yaoheng Yang, first author of the paper and a graduate student in biomedical engineering. “Because it is noninvasive, this technique has the potential to be scaled up to large animals and potentially humans in the future.”

Building on prior research from his lab, professor of biomedical engineering Jianmin Cui and his team found for the first time that ion channel activity can be influenced by ultrasound alone, possibly leading to new and noninvasive ways to control the activity of specific cells. They discovered that focused ultrasound modulated the currents flowing through the ion channels on average by up to 23%, depending on channel and stimulus intensity. Following this work, researchers found close to 10 ion channels with this capability, but all of them are mechanosensitive, not thermosensitive.

The work also builds on the concept of optogenetics, the combination of the targeted expression of light-sensitive ion channels and the precise delivery of light to stimulate neurons deep in the brain. While optogenetics has increased discovery of new neural circuits, it has limited penetration depth due to light scattering, requiring surgical implantation of optical fibres to reach deeper into the brain.

Sonothermogenetics has the promise to target any location in the mouse brain with millimetre-scale resolution without causing any damage to the brain, Chen said. She and her team are further refining the technique and validating their work.

Source: Sci Tech Daily

Journal information: Yaoheng Yang et al, Sonothermogenetics for noninvasive and cell-type specific deep brain neuromodulation, Brain Stimulation (2021). DOI: 10.1016/j.brs.2021.04.021

Categories : Neurodegenerative DiseasesTags :

Nasal Spray Maximises Parkinson’s Drug Delivery

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Image source: Pixabay

Scientists at the University of York have been developing a nasal spray treatment for patients with Parkinson’s disease, which helps to maximise delivery of the drug in high enough dosages to be effective.

To do so, the researchers have developed an innovative new gel that can adhere to tissue inside the nose alongside the drug levodopa, helping deliver treatment directly to the brain.

Levodopa is a dopamine precursor which is converted to dopamine in the brain, where it makes up for the deficit of dopamine-producing cells in Parkinson’s patients. Generally administered when other anti-Parkinson’s medication is no longer useful, levodopa helps treat the symptoms of the disease, particularly bradykinesia, which is the impairment of voluntary motor control and slow movements or freezing. However, in the long term levodopa becomes less effective, requiring increased doses for the same effect.

Higher dosages neededProfessor David Smith, from the University of York’s Department of Chemistry, explained: “The current drug used for Parkinson’s Disease is effective to a point, but after a long period of use the body starts to break down the drug before it gets to the brain where it is most needed.

“This means increased dosage is necessary, and in later stages, sometimes, instead of tablets, the drug has to be injected.  Investigations into nasal sprays have long been of interest as a more effective delivery because of its direct route to the brain via the nerves that service the nose, but the challenge here is to find a way of making it adhere to the nasal tissue long enough to release a good dosage of the drug.”

The researchers created a levodopa-loaded gel that could flow into the nose in a liquid form and then rapidly change to a thin layer of gel inside the nose.  The method was tested in animal models by a team at King’s College London, where levodopa was successfully released from the gel into the blood and directly to the brain.

Improved uptake

Professor Smith said: “The results indicated that the gel gave the drug better adhesion inside the nose, which allowed for better levels of uptake into both the blood and brain.”

The team is now working on incorporating these materials in nasal spray devices, to progress clinical trials in humans.  The treatment of neurodegenerative diseases such as Alzheimer’s may also benefit from this approach.

Khuloud Al-Jamal, Professor of Drug Delivery and Nanomedicine from King’s College London, said: “Not only did the gel perform better than a simple solution, but the brain uptake was better than that achieved using intravenous injection of the drug. This suggests that nasal delivery of Parkinson’s drugs using this type of gel may have clinical relevance.” 

Source: University of York

Journal information: Wang, J. T-W., et al. (2021) Enhanced Delivery of Neuroactive Drugs via Nasal Delivery with a Self-Healing Supramolecular Gel. Advanced Science. doi.org/10.1002/advs.202101058.

Categories : Neurodegenerative DiseasesTags :

Exercise Slows Cognitive Decline in APOE4-related Parkinson’s Disease

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Results from a longitudinal study showed physical activity reduced  cognitive decline in early APOE4-related Parkinson’s disease.

Jin-Sun Jun, MD, of Hallym University in Seoul, and colleagues in Neurology presented the findings of a longitudinal study on a group of 173 recently diagnosed Parkinson’s patients. Of this group, those who with an apolipoprotein E ε4 (APOE4) allele had faster cognitive decline on the 30-point Montreal Cognitive Assessment (MoCA) scale than noncarriers (estimate -1.33, 95% CI -2.12 to -0.47, P=0.002). However, among the APOE4 carriers, higher physical activity was related to slower cognitive decline (estimate 0.007, 95% CI 0.003-0.011, P=0.001)..

Dr Jun noted that this reflects a number of studies that have demonstrated that Parkinson’s patients who exercise regularly show better clinical outcomes, including motor and cognitive function.

“These observations are supported by epidemiological data showing a link between physical activity and decreased risk for Parkinson’s disease,” Dr Jun told MedPage Today. “Because previous data indicate that physical activity modifies the APOE4 effect on the development and progression of Alzheimer’s disease, we hypothesized that physical activity also plays a role in modulating the association between APOE4 and cognition in Parkinson’s disease.”

Genetic factors interact with physical activity on other health outcomes, noted Jacob Raber, PhD, of Oregon Health and Science University in Portland, and colleagues, in an accompanying editorial.

“If similar gene-by-physical activity interactions were identified in Parkinson’s disease, they could pave the way for personalized treatment,” Raber and colleagues wrote. “While the effects of APOE4 on promoting beta-amyloid and tau pathology are well-established, recent studies show that APOE4 is also associated with more profound pathology of alpha-synuclein and higher measures of cognitive burden, both in mouse models and in humans with Parkinson’s disease.”

In their study, the researchers followed recently diagnosed patients in the Parkinson’s Progression Markers Initiative cohort who were not treated for Parkinson’s and who had abnormal dopamine transporter (DAT) imaging.

Self-reported physical activity was begun 2 years after enrollment and scored on the Physical Activity Scale of the Elderly. Cognitive function was measured annually with the MoCA, which is well-suited for Parkinson’s patients, and DAT imaging was performed at years 2 and 4. Assessments performed at years 2, 3, and 4 were used for analysis.

There was no significant interaction seen between physical activity and APOE4 involving change in striatal DAT activities. This suggests that striatal dopaminergic function may not be a major factor in physical activity’s protective effect on APOE4-related cognitive decline, Dr Jun and colleagues noted. “These negative results may be explained by the modest effect of APOE4 on the nigrostriatal dopaminergic system,” they wrote. “Furthermore, our follow-up duration may be too short to comprehend the impact of APOE4 on this system, considering the slow progressive nature of alpha-synucleinopathy.”

The researchers also pointed out that the exercise could offer benefits through mechanisms unrelated to the disease. “Although we cannot conclude what types or amounts of exercise help to slow progression from this study design, even non-high-intensity physical activity positively modified the impact of APOE4 on cognitive function,” Jun said.

The study’s limitations included physical activity being self-reported, cognitive function being based only on MoCA scores, and a short follow-up time. Though motor scores in the off-medication state were adjusted for, physical activity may have been less due to disease progression.

Source: MedPage Today

Categories : Lab Tests and Imaging Neurodegenerative DiseasesTags :

A Non-invasive Parkinson’s Test Inspired by Scent

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A  skin swab test has been developed for Parkinson’s disease, based on biomarker analysis of sebum, the oils that protect the skin – and it has a surprising inspiration. 

This comes about after the remarkable discovery of a woman’s ability to detect a certain smell in people who had the disease. 

Joy Milne, a retired nurse, noticed a “musky” scent on her husband years before he was diagnosed with Parkinson’s disease. A series of tests showed that she could detect the presence of Parkinson’s disease in people with 100% based on smell alone, prompting research which isolated the compounds she was smelling: higher concentrations of hippuric acid, eicosane, and octadecanal.

In order to exploit these biomarkers, researchers developed a mass spectrometry test to pick up their levels in sebum obtained with skin swabs. This has proved to be around 80% accurate.

Prof Perdita Barran said: “We believe that our results are an extremely encouraging step towards tests that could be used to help diagnose and monitor Parkinson’s.

“Not only is the test quick, simple and painless but it should also be extremely cost-effective because it uses existing technology that is already widely available.

“We are now looking to take our findings forwards to refine the test to improve accuracy even further and to take steps towards making this a test that can be used in the NHS and to develop more precise diagnostics and better treatment for this debilitating condition.”

This new test with its high reliability could help the diagnosis of Parkinson’s disease, which can be easily missed, especially in the early stages.
Daxa Kalayci, 56, was misdiagnosed several times over four years before finally finding out she had Parkinson’s in 2019.

“I was misdiagnosed with anxiety, stress-related tremors and told that my problems stemmed from going through the menopause,” she said.

“Despite my diagnosis eventually being confirmed… a quick and simple diagnostic test for Parkinson’s would have given me the chance to start my treatment earlier and enjoy life a lot more.

“But instead, I lost so many years not being able to pursue a career as a paramedic or go back to nursing.

“This test could be a game-changer for people living with Parkinson’s and searching for answers, like I was.”

Source: BBC News

Categories : Exercise Neurodegenerative DiseasesTags :

Golf Shines as Physical Activity for Parkinson’s Patients

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Putter and golf balls on golf course. Photo by Robert Ruggiero on Unsplash.

In a study comparing physical activity routine for Parkinson’s patients, golf produced greater improvements than tai chi. 

Previous studies had shown that tai chi practice was beneficial as physical activity for Parkinson’s patients, resulting in balance and mobility gains, and is also safe and popular with patients.

“We know that people with Parkinson’s disease benefit from exercise, but not enough people with the disease get enough exercise as therapy,” said study author Anne-Marie A. Wills, MD, of Massachusetts General Hospital Boston. “Golf is popular—the most popular sport for people over the age of 55—which might encourage people to try it and stick with it. We decided to compare golf to tai chi in our study because tai chi is the gold standard for balance and preventing falls in people with Parkinson’s.”

The study involved 20 people with moderate Parkinson’s disease, who were offered 10 weeks of two one-hour group classes a week, randomly assigned to either golf or tai chi.

Researchers evaluated everyone with tests, including ones for mobility. For the test, a person is timed while getting up from a chair, walking 3m and then returning to the chair and sitting down. Golfers were 0.96 seconds faster on the test at the end of the study.

“While the results for golf might be surprising, it’s important to remember that the number of participants in our study was small, and the period over which we studied them was relatively short,” Dr Wills said. “More research in larger groups of people, over longer periods of time, is needed.”

While overall satisfaction was similar in both groups, 86% of golfers compared to 33% of tai chi participants were “definitely” likely to continue the activity.

“Our finding that golfers were much more likely to continue with their sport is exciting because it doesn’t matter how beneficial an exercise is on paper if you people don’t actually do it,” Dr Wills said. “So if swinging a golf club is more appealing than practicing tai chi, by all means, go to a driving range and hit balls for an hour instead!”

Source: Medical Xpress

Categories : Medical Research & Technology Neurodegenerative DiseasesTags :

Scientists Develop AI Tool to Detect Parkinson’s Disease

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Researchers have developed an AI program that can assist physicians in performing a quantitative analysis when diagnosing Parkinson’s disease. 

As human populations continue to age due to improved medical care, there is an impending ‘Parkinson’s disease pandemic’ where numbers of individuals suffering this age-related neurodegenerative disease threaten to overwhelm healthcare systems. There is a need to distinguish between Parkinson’s and other diseases which have similar motor symptoms.
Assistant Professor Andrey Somov at the Skolkovo Institute of Science and Technology and colleagues developed a machine learning algorithm to analyse video recordings of patients performing certain tasks.

“As part of the research process, we had the opportunity to closely interact with doctors and medical personnel, who shared their ideas and experience. It was fascinating observing how two seemingly different disciplines came together to help people. We also had the opportunity to monitor all parts of the research, from designing the methodology to data analysis and machine learning,” Kovalenko said.

The advantages of the video analysis approach is that it is simple, objective, noninvasive, quick, inexpensive and versatile.

To develop the machine learning algorithm, the researchers recorded 83 patients with and without Parkinson’s performing 15 tasks that they had designed, such as filling a glass with water. These tasks were developed in a prior feasibility study using wearable sensors. The machine learning technology allows for objective analysis which picks up certain features of the disease which may not be visible to the naked eye.

Coauthor of the study Sklotech Assistant Professor Dmitry Dylov, and “Machine learning and computer vision methods we used in this research are already well established in a number of medical applications; they can be trusted, and the diagnostic exercises for Parkinson’s disease have been in development by neurologists for some time. What is truly new about this study is our quantitative ranking of these exercises according to their contribution to a precise and specific final diagnosis. This could only be achieved in collaboration between doctors, mathematicians and engineers.”

“This collaboration between doctors and scientists in data analysis allows for many important clinical nuances and details that help achieve the best results. We as doctors see great potential in this; apart from differential diagnosis, we need objective tools to assess motor fluctuation in patients with PD. These tools can provide a more personalized approach to therapy and help make decisions on neurosurgical interventions as well as assess the outcomes of surgery later,” noted coauthor of the paper, neurologist Ekaterina Bril.

Source: News-Medical.Net

Journal information: Kovalenko, E., et al. (2021) Distinguishing Between Parkinson’s Disease and Essential Tremor Through Video Analytics Using Machine Learning: a Pilot Study. IEEE Sensors.doi.org/10.1109/JSEN.2020.3035240.

Categories : Ageing Neurodegenerative DiseasesTags :

Parkinson’s Disease Spotted in Advance with Health Checkup

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A study by the University of Nagoya has shown that general health checkups may be effective at spotting early signs of Parkinson’s disease (PD) in advance.

Specifically, the prodromal stage shows sex differences, with the markers for males being decreased cholesterol and haematocrit (the percentage of red blood cells in blood) levels, while in females it is increased blood pressure. PD is the second most common disease affecting the nervous system after Alzheimer’s disease, is caused by a deficiency in the neurotransmitter dopamine. By the stage where sufferers experience motor symptoms such as tremors, stiffness, bradykinesia (slowness of movement), more than half of all dopaminergic neurons have been lost. Postural instability occurs in the late stage. Several processes have been implicated in PD, such as mitochondrial dysfunction, defective protein clearance mechanisms, and neuroinflammation, but it is not clear how these factors interact.

Prior studies have shown that non-motor symptoms including constipation, rapid eye movement sleep behaviour disorder, impairment of sense of smell, and depression, emerge in patients with PD 10 to 20 years before the onset of motor symptoms – meaning that PD may be detectable in advance with other measures.

“If we can detect biological changes in the patients’ bodies well before the onset of the motor symptoms, we can start medical treatments in an early stage,” said Prof Masahisa Katsuno of the Graduate School of Medicine at Nagoya University.

The team used health checkup data from 22 male and 23 female patients with PD, dating to before they were diagnosed with the disease. They supplemented this with data from 60 male and 60 female healthy individuals who had checkup data for at least four years.The checkup data was compared between healthy individuals and PD patients to establish a baseline, and then were examined for longitudinal changes prior to the onset of PD. They found that in the premotor stage, blood pressure increased in females, while in males total and low-density cholesterol levels and haematocrit decreased.

“In this study, we found that blood pressure, haematocrit, and serum cholesterol levels are potential biomarkers of Parkinson’s disease before the onset of its motor symptoms,” said Prof Katsuno. “This finding indicates that general health checkups can help detect early signs of developing Parkinson’s disease.”  Based on the findings, the team is now working to identify individuals at risk of developing PD in an attempt to forestall the development of their disease.

Source: Medical Xpress

Journal information: Katsunori Yokoi et al. Longitudinal analysis of premotor anthropometric and serological markers of Parkinson’s disease, Scientific Reports (2020). DOI: 10.1038/s41598-020-77415-1