Simple Breath Test May Aid in Early Diagnosis of Parkinson’s, Study Reports

breath test

A new device that uses just a breath sample might, in the future, help diagnose early-stage Parkinson’s patients or identify those who may be at risk, according to researchers.  

The innovative technology, developed by researchers at the Israel Institute of Technology, was able to detect alterations in the breath of newly diagnosed Parkinson’s patients, even before they begin medication.

Although the device and collection method still needs to be perfected to reach the sensitivity of other diagnostic approaches such as brain ultrasound scans, researchers believe the tool shows promise.

Findings were reported in the study, “Sensor Array for Detection of Early Stage Parkinson’s Disease before Medication, published in the journal ACS Chemical Neuroscience.

The team had already tested its device in the past, and were able to detect differences in the exhaled breath of people already being treated for Parkinson’s disease and healthy controls.

Now they wanted to see if the device could detect differences in the breath of patients with early-stage Parkinson’s who were not yet on any medications.

The device consists of an array of 40 cross-reactive sensors based on gold nanoparticles or single-walled carbon nanotubes, attached to different chemical ligands. Each of these ligands can bind certain airy or volatile molecules in the breath that change the electrical signals of the sensor.

They tested the device on 29 patients who had recently been diagnosed with idiopathic Parkinson’s disease — with no known cause — and were not yet on medication, and 19 healthy individuals of similar ages, used as controls.

The device’s performance was also compared with other currently used diagnosed tests, namely brain ultrasonography and smell detection.

The sensor was able to distinguish Parkinson’s patients from controls with a sensitivity of 79%, a specificity of 84%, and accuracy of 81%, better than smell detection tests, which have 62% sensitivity, 89% specificity and 73% accuracy, and almost as good as brain ultrasound scans, at 93% sensitivity, 90% specificity, and 92% accuracy.

“[O]ur studies provide additional confirmation of the ability of our sensors array to detect altered breath VOC [volatile organic compounds] composition characteristic of PD [Parkinson’s disease],” the researchers wrote.

Early diagnosis of Parkinson’s can help patients begin neuroprotective therapies sooner, before extensive loss of dopamine-producing nerve cells — those affected in Parkinson’s disease — has occurred in the brain. However, to date, diagnosis is still subject to considerable errors.

So far, studies on early Parkinson’s diagnosis using volatile biomarkers have only been done in patients who are already being treated and medicated. “There is a great need to evaluate untreated patients for establishing a real world screening and diagnostic technology,” the authors said.

Further improvements, as well as more testing in patients, are still necessary for the device to reach the sensitivity of other diagnostic methods like brain ultrasound scans.

“Future development of the sensors array technique has the potential to produce a small, portable system with the advantage of unbiased determination which could be used in initial screening of at-risk subjects without the need for experienced clinical personnel,” the researchers concluded.

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Imaging Tracer with Potential to Bolster Clinical Trials of Parkinson’s and Its Treatments Favored by EMA

123I-FP-CIT SPECT tracer

The European Medicines Agency (EMA) endorsed an imaging test that can help in identifying Parkinson’ patients with early stage disease but likely to progress quickly — people who might be best suited to taking part in clinical trials.

Development of this clinical assessment tool — which targets disease biomarkers — came through collaborative work involving Critical Path for Parkinson’s (CPP) Consortium, a part of the Critical Path Institute (C-Path), the non-profit group Parkinson’s UK, and several pharmaceutical companies.

“This endorsement from the European Medicines Agency represents many years of hard work and incredible collaboration among companies, universities, and charities facilitated by the Critical Path Institute,” Diane Stephenson, executive director of CPP, who led the effort, said in a press release.

“Through our global project, we’ve been able to bring all the data and expertise together to make a powerful case, so we’re delighted that this endorsement from the EMA will improve the quality and chances of success for future trials of Parkinson’s treatments,” Stephenson added.

The method requires the intravenous injection of a radioactive tracer called 123I-ioflupane, or 123I-FP-CIT, which can be detected by single-photon emission computed tomography (SPECT) imaging. The tracer binds very specifically to dopamine transporter sites on the neurons that are lost to Parkinson’s disease, allowing scientists to detect alterations in dopamine transport — a hallmark event in the disease’s development.

Working as a kind of enrichment biomarker for early stages of Parkinson’s disease, the radioactive tracer helps to differentially diagnose between essential tremor and other parkinsonian disorders, such as progressive supranuclear palsy or multiple system atrophy, and Parkinson’s “subjects with high likelihood of progressing in clinical motor disability.”

The tracer has been available in the European Union since 2000 with the brand name DaTSCANTM, and in the United States since 2011 as DaTscan. In 2015, the U.S. Food and Drug Administration issued a letter of support for the use of this imaging biomarker as a “prognostic biomarker for enrichment in trials for Parkinson’s disease.”

“These brain scans in themselves are not new, but until now there has not been a clear consensus that they can and should be used to select participants for clinical trials,” Stephenson said.

“The use of these brain scans is already being included in new clinical trials at Biogen,” said Michael Ehlers, MD, PhD, executive vice president of research and development at Biogen. “We believe that this new approach will introduce greater efficiency in terms of cost and speed, while ensuring that the right patients are being included in our trials.”

Due to the progressive nature of Parkinson’s, the best approach to slow, stop, or reverse the disease would be by intervening as early as possible. But disease manifestations can be subtle in its early stages, complicating trial recruitment.

Previous reports suggest that up to 15 percent of patients taking part in trials of new Parkinson’s therapies may not be the best candidates to measure potential efficacy, because of scant change in their motor symptoms during the time-limited course of such studies. In its early stages, disease progression can be difficult to predict.

“Being able to rule out individuals who are unlikely to have Parkinson’s could be the difference between a successful trial and failure,” said David Dexter, PhD, a professor at Imperial College London and deputy research director of Parkinson’s UK. “This is a vital step forward in our mission to deliver, as quickly as possible, better treatments, and one day a cure, to people living with Parkinson’s.”

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Feedback from Parkinson’s Patients Can Help Improve Trial Recruitment, Retention, Study Says

clinical trial feedback

Getting the perspective of Parkinson’s disease patients on their motivations and experiences participating in clinical trials can help increase recruitment and retention of future studies, a report suggests.

Although preventable, one of the most common reasons Phase 2 or 3 trials fail is because not enough patients participate. This could be due to inadequate recruitment or because patients drop out during the trial.

The report, “Recruitment and Retention in Clinical Trials of Deep Brain Stimulation in Early-Stage Parkinson’s Disease: Past Experiences and Future Considerations,” published in the Journal of Parkinson’s Diseaseevaluated patient responses after a pilot study on the safety and tolerability of subthalamic (STN) deep brain stimulation (DBS) for the treatment of early-stage Parkinson’s disease.

DBS is commonly used to treat patients with advanced Parkinson’s who no longer respond to available medications and are unable to adequately manage their symptoms.

The U.S. Food and Drug Administration also recently expanded the use of DBS — which requires surgery to implant a device to stimulate targeted regions of the brain — to patients with mid-stage disease who also respond poorly to standard medications.

Vanderbilt University in Nashville, Tennessee, completed a clinical trial (NCT00282152) that included 30 patients, ages 50 to 75, with early-stage Parkinson’s disease. The participants were randomized to receive either optimal drug therapy (ODT) or ODT plus STN-DBS and followed for two years.

At the end of this pilot study, participants were asked to complete a survey regarding their experiences participating in the trial. Their responses were compared with those from an independent survey that used Fox Insight, an online clinical study platform established by The Michael J. Fox Foundation for Parkinson’s Research, to survey early-stage Parkinson’s patients who were considering possibly participating in a trial for DBS.

The pilot trial was specifically designed to collect preliminary safety and tolerability data necessary to conduct an FDA-approved Phase 3 trial (IDE#G050016) to investigate the hypothesis that DBS in patients with early Parkinson’s can slow disease progression.

Importantly, patient experiences were expected to inform the feasibility of scaling up recruitment for the future trial.

Results revealed that the primary motivation for participating in a clinical trial was the desire to advance medical research, cited by 85% of trial respondents. This was followed by a desire for the best medical treatment, for 70%, and for 59%, a desire to learn more about Parkinson’s disease. Similarly, altruistic motivations were also seen in the Fox Insight survey.

The most frequently listed fear that could impact trial participation was surgery-related concerns, in 44% of participants. Although 37% of the pilot study participants did not report any burdens, the most common burdens associated with clinical trials were financial commitments such as time off work and traveling costs (30%), as well as some of the therapeutic interventions such as neuropsychological testing (26%), and the weeklong therapeutic washout periods — without medication (26%).

The pilot study implemented a rigorous informed consent progress aimed at educating potential participants on their role in the study. Most participants responded positively to this approach. Providing sufficient education at the start of the trial may decrease the drop-out rate. In fact, only 3% of participants did not complete the study. As a result, this approach of informed consent will be used in the upcoming Phase 3 trial, according to the authors.

Getting patient perspectives is a new strategy that could improve clinical trial recruitment and retention. Whereas most clinical trials were solely designed by physicians, now, as the authors suggest, by asking patients about their experiences and including their feedback in trial development, “the focus shifts away from the physician and toward the patient.”

“By understanding the motivations and barriers to trial participation of past and potential subjects, we attempt to predict feasibility of recruitment in the future pivotal trial,” the authors wrote. “The fundamental similarities of these two cohorts of patients with early-stage [Parkinson’s disease] suggest that the planned multicenter, pivotal trial will experience similarly successful recruitment and retention as the single-center pilot trial.”

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Disabled Body in an Able-bodied Restaurant

restaurant

Sherri Journeying Through

My husband and I recently tried out a new restaurant in town (new to us) for lunch to celebrate our 38th wedding anniversary. We decided to sit outside as the weather was nice and it wasn’t smoldering hot. That day, anyhow.

We pulled out the cast-iron chairs that had been scooted under the table and sat down. Sort of. The legs scraped against the concrete below and would barely budge for me. My ability to pull the chair in was nil. My husband tried to help but was unable to assist me. I told him it was OK and I was close enough to the table.

I unwrapped my napkin that held my silverware and put it on my lap. I put my silverware back on the criss-cross steel grate tabletop. Eventually, we placed our order and soon thereafter were served our salad. We said grace and I reached over to pick up my fork, having no luck since my fingers could not grasp it without a solid table top to brace my fingers against. After several attempts, my husband offered to help, and I finally conceded. I was hungry, after all.

We ate our scrumptious lunch and then headed home, with only two slight spills of Alfredo sauce down the front of my shirt from having to sit so far from the table. Now I was able to clearly see, experience, and fully understand another reason why people with Parkinson’s disease don’t like to go out for meals. In addition to the possibility of choking on your food in public, excessively drooling, and not being able to hold your drinking cup or utensils adequately (without bringing attention to yourself or those with you), grated tables and cast-iron chairs that won’t scoot against concrete floors add another obstacle people with Parkinson’s must fight. And that includes not only people with PD, but also other chronic illnesses or disabilities others have to live with daily.

Wouldn’t it be great if, when designing a restaurant, the builders, architects, owners, and designers of establishments would consider those who are disabled as a forethought and not necessarily an afterthought?

I was in another restaurant this past week with my son and his family and needed to use the restroom. I waited as long as I could, as I knew I would have a hard time getting to it with the restaurant being wall-to-wall with tables and chairs, and each of those chairs filled up and pushed out into what little aisles there were. I only tripped once and knocked someone’s ponytail to the side while trying to get by, walking sideways to get there.

I wonder how many people with disabilities have stopped trying to have a nice meal out because the restaurant they would like to patronize doesn’t take into consideration the needs of a disabled or handicapped person? Having a wheelchair sticker on the end of one or two tables is a start, but in most cases, that may not be enough anymore.

As a person with Parkinson’s disease, have you had issues when eating out? What were they and how did you deal with them?

***

Note: Parkinson’s News Today is strictly a news and information website about the disease. It does not provide medical advice, diagnosis or treatment. This content is not intended to be a substitute for professional medical advice, diagnosis, or treatment. Always seek the advice of your physician or another qualified health provider with any questions you may have regarding a medical condition. Never disregard professional medical advice or delay in seeking it because of something you have read on this website. The opinions expressed in this column are not those of Parkinson’s News Today or its parent company, BioNews Services, and are intended to spark discussion about issues pertaining to Parkinson’s disease.

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Identifying Biomarkers of Inflammation Among Goals of Parkinson’s Study by Longevity Biotech and Veterans’ Center

Longevity Biotech study

Longevity Biotech announced plans for a clinical study aiming to identify potential blood-based markers of inflammation that originates in the immune system, biomarkers that may work to better diagnose Parkinson’s and recognize the disease’s different stages.

The study, being run with the support of The Michael J. Fox Foundation for Parkinson’s Research, will also advance early evaluations of the company’s therapeutic candidate LBT-3627.

The two-year study will launch at the Corporal Michael J. Crescenz Veterans Affairs Medical Center,  part of the Philadelphia Parkinson’s Disease Research, Education and Clinical Centers.

The immune system plays a critical role in neurodegenerative diseases, including Parkinson’s. The study will use machine learning techniques to identify immune-based inflammatory biomarkers “that could provide clinically relevant diagnostic information,” Scott Shandler, PhD, co-founder and CEO of Longevity Biotech, said in a press release.

“The identification of these [immune-based inflammatory] markers would have a tremendous impact on the pace of disease modifying therapeutic development for Parkinson’s disease patients by providing a new metric to track disease progression while possibly identifying new disease targets as well,” he added.

Study researchers will be looking not only to expand knowledge into the underlying mechanisms of Parkinson’s, but also to correlate new and existing blood-based markers, such as the protein alpha-synuclein, with standard clinical scores from the Unified Parkinson’s Disease Rating Scale (UPDRS). This scale uses questions to assess both motor and non-motor symptoms associated with Parkinson’s.

In a preclinical setting — ex vivo, meaning outside a living organism — researchers will also examine the potential efficacy of LBT-3627 using human immune cells. The investigative compound is a small protein designed to mimic naturally occurring molecules that activate a family of receptors known for their neuroprotective and anti-inflammatory activities. As such, LBT-3627 is expected to work to balance immune responses and reduce inflammatory damage done to the brain by immune cells.

Previous studies in mice disease models found evidence that LBT-3627 can protect dopaminergic neurons from degeneration, one of the hallmarks of Parkinson’s disease.

“The goal is to convert T cells, which are key actors in the adaptive immune system, from an inflamed, neurodegenerative state to a more healthy, neuroprotective one,” said Jenell Smith, PhD, a lead scientist at Longevity Biotech.

“LBT-3627 has demonstrated robust neuroprotective results in animal models of Parkinson’s disease to date and we will continue testing the effects of LBT-3627 on human immune cells as part of this study,” Smith concluded.

The release did not specify if this study is already underway.

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8 or More Years of Contact Sports Linked to Parkinson’s-like Symptoms in Study

contact sports and brain injury

Athletes playing contact sports for longer than eight years are six times more likely to develop Lewy body disease — a neurodegenerative disorder causing Parkinson’s-like symptoms — compared to those playing football, ice hockey or boxing for fewer years, a study reports.

Its authors suggest that years of continual injury to the brain, rather than those causing concussions, might be a determining factor.

The study, “Lewy Body Pathology and Chronic Traumatic Encephalopathy Associated With Contact Sports,” was published in the Journal of Neuropathology & Experimental Neurology.

Mild traumatic brain injuries (TBI), like concussions, that occur during contact sports are a growing health concern.

Playing contact sports for multiple years — regardless of concussion history — is already associated with brain imaging abnormalities. Consequently, players are considered to be at an increased risk of developing neurodegenerative diseases such as chronic traumatic encephalopathy (CTE), amyotrophic lateral sclerosis, Parkinson’s, and parkinsonism.

CTE develops as a result of repetitive head impacts, mainly through contact sports, and is characterized by abnormal changes in behavioral, mood, and cognitive and motor skills.

A 2016 study found an association between TBIs resulting in a loss of consciousness in people under age 25 and an increased risk of Lewy bodies — which correspond to aggregates of α-synuclein — in the brain.

Deposits of α-synuclein, called Lewy body disease (LBD), is associated with cognitive and motor abnormalities, and linked to later possible dementia and Parkinson’s disease.

Both trauma and CTE are also known to influence α-synuclein deposition in the brain, which can explain the motor symptoms sometimes found in athletes with chronic traumatic encephalopathy.

Researchers with Boston institutes examined whether contact sports and CTE are also linked with Lewy body disease. They assessed the presence and distribution of Lewy bodies in the brains of 269 deceased contact sports athletes (professional or amateur), 164 brain donations representing the community, and 261 from brain bank at the Boston University Alzheimer Disease Center.

The athletes had participated in sports that included American and European football, ice hockey, boxing, rugby, and the martial arts.

Contrary to what researchers expected, the regional distribution of Lewy bodies in the brains of CTE patients was similar to that seen in those with LBD.

Contact sports athletes were 1.3-fold more likely to develop neocortical LBD for each year they played. Neocortical LBD refers to deposition of Lewy bodies in the brain’s neocortex, the area responsible for such higher-order functions as cognition and motor commands.

A pooled analysis also showed that people who played contacts sports for more than eight years were the most likely to develop of neocortical LBD.

In fact, athletes in contact sports  for more than eight years were 6.24-fold more likely to develop neocortical LBD compared to those playing in them for eight or fewer years, even after adjusting for possible confounding factors.

“The number of years of play of contact sports, not concussion history, best predicts CTE stage and the severity of tau pathology in the frontal cortex,” the study states.

Researchers also found that the presence of neocortical LBD, CTE stage, and Alzheimer’s disease were all significantly associated with dementia.

But parkinsonism (a Parkinson’s-like movement disorder) was associated only with neocortical LBD –  suggesting that Lewy body disease is likely responsible for the motor symptoms seen in CTE patients.

“We found the number of years an individual was exposed to contact sports, including football, ice hockey, and boxing, was associated with the development of neocortical LBD, and LBD, in turn, was associated with parkinsonism and dementia,” Thor Stein, MD, PhD, a study author, neuropathologist at VA Boston Healthcare System and assistant professor at Boston University School of Medicine (BUSM), said in a press release.

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Therapies Targeting LRRK2 Gene Could Benefit Broad Population of Parkinson’s Patients, Study Finds

LRRK2 gene

The LRRK2 gene may play an important role in nonhereditary Parkinson’s disease, not just the familial form as previously thought, researchers at the University of Pittsburgh School of Medicine​ have discovered.

“This discovery is extremely consequential for Parkinson’s disease because it suggests that therapies currently being developed for a small group of patients may benefit everybody with the disease,” J. Timothy Greenamyre, MD, PhD, the study’s senior author, said in a press release. Greenamyre is the Love Family Professor of Neurology at Pitt’s School of Medicine, chief of the movement disorders division at the University of Pittsburgh Medical Center, and director of the Pittsburgh Institute for Neurodegenerative Diseases.

These new findings were reported in the study, “LRRK2 activation in idiopathic Parkinson’s disease,” published in Science Translational Medicine.

Parkinson’s disease is a chronic and progressive neurodegenerative condition caused by the loss of dopamine-producing neurons in the substantia nigra, a brain region involved in the control of voluntary movements. It is estimated to affect 1 million people in the U.S. and up to 10 million worldwide.

There are two basic types of Parkinson’s: the familial hereditary form of the disease, which is associated with genetic mutations that make individuals more prone to develop Parkinson’s; and the idiopathic nonhereditary form of the disease, where the causes are unknown.

Genetic mutations in the leucine-rich repeat kinase 2 (LRRK2) gene — which provides instructions for making a kinase, a type of protein that regulates the function of many others — that cause an overactivation of the protein have been associated with the familial form of Parkinson’s.

However, researchers still do not know if the normal, nonmutated LRRK2 gene could also play a role in the idiopathic form of the disease.

To answer this, investigators set out to analyze the activity of LRRK2 in postmortem brain samples from patients with idiopathic Parkinson’s, who did not have genetic mutations in LRRK2, and healthy individuals from the same age group used as controls.

But studying LRRK2 is difficult because its levels in the brains of Parkinson’s patients are extremely low and hard to detect.

To overcome this, Greenamyre’s team took advantage of a technique called proximity ligation assay, which works by attaching special fluorescent molecules to LRRK2 that glow red when the protein is active, allowing researchers to spot them under a microscope.

Investigators found that LRRK2 activity was increased in dopamine-producing neurons from the substantia nigra of patients with idiopathic Parkinson’s, in comparison with healthy controls.

Interestingly, they observed the same trend in two different rat models of the disease, suggesting that LRRK2 overactivity seems to be important not only for patients with genetic mutations in LRRK2, but also for other individuals with the idiopathic form of the disease.

They then found that LRRK2 activity is linked to alpha-synuclein — a protein that accumulates inside nerve cells, producing small structures called Lewy bodies — that is considered a hallmark of Parkinson’s disease.

Using an animal model of Parkinson’s, they discovered that LRRK2 activation actually blocks the mechanism cells use to clear excessive alpha-synuclein, eventually leading to an abnormal buildup of the protein inside nerve cells.

Researchers then treated these animals with an investigational treatment intended for patients with familial Parkinson’s that works by blocking LRRK2 activity. Remarkably, they observed that the therapy was able to prevent both the accumulation of alpha-synuclein and the formation of Lewy bodies inside nerve cells.

These findings show that, regardless of genetic mutations, the LRKK2 gene plays a role in both types of Parkinson’s disease, indicating that LRRK2 inhibitors may be useful to treat patients with the idiopathic or familial form of the disease.

“We believe that LRRK2 inhibitors may be beneficial not only for the 3 to 4% of people with [Parkinson’s disease] who carry LRRK2 mutations but also for [idiopathic Parkinson’s disease] patients who do not carry LRRK2 mutations,” the authors wrote in the study.

In the future, Greenamyre’s team aims to investigate how LRRK2 overactivity can be prevented, as well as determining the underlying mechanisms that cause its activation in Parkinson’s patients.

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Key to Effective Parkinson’s Treatment May Lie in Stem Cells, Researchers Say

stem cells

One of the most promising therapeutic avenues for Parkinson’s disease is the use of stem cells to replace dopamine-producing neurons, the loss of which is a hallmark of the disease.

This is the focus of a special issue on Parkinson’s disease published in the journal Stem Cells and Development available for free download until Aug. 24.

“The understandable excitement generated by recent successful phase 1 clinical trials in the treatment of Parkinson’s disease (PD) is tempered with worldwide concern for the safe translation of stem cell research to an effective treatment for this terrible disease and other neurological conditions,” Graham C. Parker, PhD, editor-in-chief of the journal, said in a press release. “The research in this special issue reflects the responsible advancement of cell therapy for PD.”

Parkinson’s disease is a chronic and progressive neurodegenerative disorder, caused by the gradual loss of dopaminergic neurons in the substantia nigra, a region of the brain responsible for movement control.

Current standard therapies for Parkinson’s disease often focus on restoring dopamine signaling in the brain to reduce the severity of symptoms and improve patients’ quality of life. However, these treatments do not cure the disease.

The most promising therapeutic approach to truly reverse Parkinson’s progression involves replacing these dopamine-producing neurons that have been lost over the course of the disease. Two articles in the special issue explore this new route, pointing out its advantages and practical challenges.

The first article, “Autologous Induced Pluripotent Stem Cell-Derived Neurons to Treat Parkinson’s Disease,” written by Jeanne F. Loring, PhD, from the Scripps Research Institute in California, discusses the use of patient-derived induced pluripotent stem cells (iPSCs) to treat Parkinson’s disease, and upcoming clinical trials to test this method.

These iPSCs are fully matured cells that researchers are able to reprogram in vitro to revert them back to a stem cell state, where they are able to grow into any type of cell, including dopaminergic neurons.

“It is a personalized therapy, in which we generate iPSCs from each patient and will transplant immunologically matched neurons. This means that there are no costs or potential side effects from giving the patients immunosuppressive drugs,” Loring wrote.

The biggest downside to this technology is its cost, which is still fairly high, but Loring says the economic burden would not be higher in comparison with other personalized cell therapies, such as CAR-T cell therapies — priced at roughly $500,000.

“We hope to begin a clinical trial by the end of next year, 2019, and our current efforts are focused on producing data for regulatory agencies that will assure them of the safety and efficacy of the autologous [patient-specific] dopamine neurons. If we are successful, the restoration of health to people living with PD will be priceless,” she said.

The second article, “Novel Approach to Stem Cell Therapy in Parkinson’s Disease,” written by Russell Kern, PhD, of the International Stem Cell Corporation in California, and colleagues, focuses on an alternative approach to stem cell therapy.

Instead of using iPSCs to generate patient-specific neurons, they propose using parthenogenetic-derived neural stem cells — stem cells obtained by chemical manipulations in unfertilized human oocytes, an immature egg cell, which are also able to grow into neurons.

The major advantages of this approach include avoiding ethical concerns since no fetus or viable embryo is used in their derivation (which is also the case with iPSCs), the reduced number of possible mutations in comparison with iPSCs, and also their low immunogenicity, which is the ability of a particular substance to trigger an immune response.

The authors are confident this alternative technique will be beneficial for the treatment of Parkinson’s patients, pointing to promising evidence in preclinical studies that supported a first human Phase 1 clinical trial (NCT02452723) evaluating the safety of a pluripotent stem cell-based treatment in Parkinson’s patients already underway.

“Our therapeutic approach is not only based on cell replacement but also on neuroprotection, neurotrophic support, and immunomodulation and has the potential to rescue the nigrostriatal and extranigral [dopaminergic] systems and significantly improve motor and cognitive functions, as well as quality of life, offering hope to patients worldwide suffering from this devastating disease,” they wrote.

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Beat It! Learning to Walk to Music Reduces Falls for Parkinson’s Patients

walking and music

A training program in which patients walk while listening to regular beats can improve the velocity and cadence of Parkinson’s disease patients, while reducing their risk of falling, a study shows.

The study, “Rhythmic auditory stimulation for reduction of falls in Parkinson’s disease: a randomized controlled study,” was published in the journal Clinical Rehabilitation.

Parkinson’s disease patients experience difficulties in movement that affect their ability to produce a steady gait, resulting in a high incidence of falls. More than half of all Parkinson’s patients fall recurrently.

While there are several training techniques to aid in maintaining a steady gait and avoiding falls, studies suggest that gait motor control is dependent on a patient’s internal timing and that rhythm-based training could reduce risk of falling.

The rhythmic auditory stimulation (RAS) technique is among the approaches used to synchronize gait movements with time cues. But there have been no studies assessing the benefits of RAS in Parkinson’s patients.

So, researchers in Canada set out to determine if a home-based RAS program could aid in decreasing falls in patients with that history.

The study was a randomized, controlled trial (NCT03316365) that involved 60 Parkinson’s patients, 47 of whom completed the study.

The RAS training protocol involved 30 minutes of daily walking using “click-embedded music,” which was designed to enhance rhythm perception. Essentially, patients listened to folk or classical music with embedded metronome beats while performing their walking exercises.

Participants were divided into two groups, experimental and control. Both groups received RAS training up to week 8, after which the control group stopped training and the experimental group continued. Then  training was resumed for the control group between weeks 16 and 24. Patients in the experimental group received RAS training for the entire 24 weeks.

Participants were assessed at the beginning of the study and at eight, 16, and 24 weeks following that. Assessment criteria included stride length, speed, balance, and falls.

As expected, no significant differences were seen between the two groups at week eight. However, at week 16, the experimental group showed significant improvement in velocity, cadence, stride length, decreased number of falls, and fear of falling compared to the control group.

At week 24 — after the control group had resumed RAS training — the signifiant differences in velocity, cadence, stride length, and fear of falling remained, but there were no longer significant differences in the number of falls.

Taken together, the findings indicate that “RAS gait training significantly reduced the number of falls and modified key [parameters] in gait control in patients with Parkinson’s disease,” researchers wrote.

“This clinical investigation demonstrates that RAS gait training is a potential intervention to reduce the risk of falling, since it directly addresses temporal instability, which is one of the most detrimental variables associated with falls,” they concluded.

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People with Reduced Smell, Taste Abilities at Risk of Parkinson’s Detected by Machine Learning

machine learning in PD

Machine learning identifies individuals with reduced odor and taste sensitivity as people at risk for developing Parkinson’s disease, researchers from Italy report. The approach could be part of a noninvasive method to study early-onset Parkinson’s, the findings suggest.

The study, “Comparative Motor Pre-clinical Assessment in Parkinson’s Disease Using Supervised Machine Learning Approaches,” appeared in the journal Annals of Biomedical Engineering.

Currently, the diagnosis of Parkinson’s is based mainly on its motor symptoms, Specifically, clinicians use scales such as the Movement Disorder Society-sponsored revision of the Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) to determine disease severity. However, the score is subjective and the detection of small changes in motor performance may be challenging.

Nonmotor symptoms such as idiopathic hyposmia (IH) — reduced ability to smell and taste — have been the focus of increased attention due to their potential to anticipate motor manifestations.

However, issues related to their low specificity for Parkinson’s preclude their use to identify individuals with early, or prodromal, disease.

Imaging techniques such as single proton emission computed tomography (SPECT) are currently used to confirm diagnosis, but they require highly skilled staff, and may be invasive, expensive, or not sufficiently specific.

Machine learning, a subset of artificial intelligence, has been used to differentiate Parkinson’s patients from healthy controls regarding the motor ability of their lower limbs. However, no study has applied machine learning algorithms — a list of rules computers follow to solve problems — to people at risk of developing Parkinson’s, specifically those with IH, according to the authors.

So, the research team tested the ability of three machine learning approaches to differentiate lower limb performance in diagnosed Parkinson’s patients, people with IH, and healthy people, or controls (30 subjects each).

Motor performance in four exercises — leg agility, toe tapping, gait and rotation, all part of MDS-UPDRS section III — was measured through wearable sensors called inertial measurement units.

Results showed that all three approaches accurately distinguished patients, people with IH, and controls. Individuals with IH showed an intermediate motor performance between controls and patients.

“Thus, IH subjects can be identifiable as people at risk of developing the pathology in a prodromal phase,” the researchers wrote.

“Further, identification of IH together with changes in motor parameters could be a noninvasive two-step approach to investigate the early onset of [Parkinson’s disease],” they added.

Of note, the findings also indicated that all four exercises were important to classify the participants. According to the scientists, this will encourage researchers to also use tapping exercises in assessments of motor performance, unlike most studies that used gait only.

Among the study’s limitations, the researchers mentioned the lack of correlation with clinical scales, as the analysis did not consider Parkinson’s severity or the level of IH. Future research should have larger sample sizes and analyze upper limb motor performance as well, they advised.

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Source: Parkinson's News Today