Research

Study: People skip Parkinson’s, Alzheimer’s meds as prices rise

March 1, 2020 Life, Research

Rising drug costs are hampering the care of patients with debilitating neurological disorders like Parkinson’s disease and Alzheimer’s, a new study finds.

Patients are less likely to fill necessary prescriptions as out-of-pocket costs increase, said senior researcher Dr. Brian Callaghan, a neurologist with the University of Michigan, in Ann Arbor.

“It’s a pretty predictable 5 percent to 10 percent drop for every $50 increase in cost,” Callaghan said.

For patients with Parkinson’s disease, not taking medications as prescribed can severely impact their quality of life, he noted.

“The Parkinson’s medicines are supposed to help make their tremors better, help them walk faster better. Theoretically, it could prevent falls and hospitalizations,” Callaghan said. “It’s not really preventing people from dying. It’s enabling people to live better and have better symptom control.”

Previous studies have shown that out-of-pocket drug costs are rising for neurologic medications, Callaghan said.

To see how these higher prices affect patient care, Callaghan and his colleagues singled out three neurologic diseases for which there are effective drugs available at a wide variety of prices:

  • Parkinson’s disease, where the drug pramipexole cost $35.90 for a 30-day supply in 2016, compared to $12.40 for the drug ropinirole.
  • Alzheimer’s disease, where a month’s supply of rivastigmine was $79.30, compared to $3.10 for the drug donepezil.
  • Peripheral neuropathy, where pregabalin cost $65.70 for a month compared to $8.40 for gabapentin.

The researchers used a private insurance claims database to track more than 80,000 patients’ prescriptions during a 15-year period, comparing how often they filled prescriptions with their out-of-pocket costs.

In 2015, the Alzheimer’s drug donepezil cost about $3 for a 30-day supply, and researchers found that people filled their prescriptions about 70 percent of the time. On the other hand, the drug rivastigmine cost about $100, and people filled those prescriptions only 45 percent of the time.

A $50 increase in out-of-pocket costs was associated with an overall 12 percent decrease in a patient’s access to Alzheimer’s medications, the researchers found.

The same pattern held for Parkinson’s patients and people with peripheral neuropathy, which causes numbness and pain, usually in the hands and feet.

“I am not surprised,” James Beck, chief scientific officer for the Parkinson’s Foundation, said of the study results. “The free Parkinson’s Foundation Helpline team hears similar stories from people with Parkinson’s disease every day. The cost of medications is a key factor in their budgets and everyday lives.”

The medication regimen for people with Parkinson’s is especially complex, “and the timing of multiple pills a day often taking into account meals is incredibly arduous,” Beck said. “Therefore, missing doses of medications will have the effect of a reduction in quality of life. People may not be able to move as well, sleep as well, or do the activities they enjoy as a result of missing their medications.”

Callaghan pointed out that medication adherence is probably even worse for patients with disorders like multiple sclerosis, where there are only a handful of medicines available and all are expensive.

Callaghan and Beck recommended that patients talk with their doctor and pharmacist if they’re struggling to pay for their medications. There could be cheaper drugs available that would work as effectively.

“For Parkinson’s disease, there are three types of medications that people often take as their first medication. The evidence suggests that starting with any of these medications leads to similar positive outcomes,” Beck said. “Therefore, people with Parkinson’s disease and their providers can work together to identify what might be the most affordable medication to start with in treating their Parkinson’s disease symptoms.”

The study was published online Feb. 19 in the journal Neurology.

Article from UPI.

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Pingpong May Help Reduce Some Parkinson’s Symptoms

March 1, 2020 Life, Research

The game of pingpong, or table tennis, may hold promise as a form of physical therapy for Parkinson’s disease, according to a preliminary study presented at the American Academy of Neurology’s 72nd Annual Meeting in Toronto, Canada.

The findings show that 12 Parkinson’s patients who participated in a pingpong exercise program once a week for six months experienced improvements in several symptoms, including facial expressions, posture and rigidity. They were also better at getting dressed and getting out of bed.

Parkinson’s disease is a movement disorder in which the brain chemical dopamine gradually declines. This process results in slowly worsening symptoms that include tremor, stiff limbs, slowed movements, impaired posture, walking problems, poor balance and speech changes.

“Pingpong, which is also called table tennis, is a form of aerobic exercise that has been shown in the general population to improve hand-eye coordination, sharpen reflexes, and stimulate the brain,” said study author Ken-ichi Inoue, M.D., of Fukuoka University in Fukuoka, Japan.

“We wanted to examine if people with Parkinson’s disease would see similar benefits that may in turn reduce some of their symptoms.”

The research involved 12 individuals with an average age of 73 with mild to moderate Parkinson’s disease. The participants had been diagnosed with Parkinson’s for an average of seven years. They were tested at the start of the study to see which symptoms they had and how severe the symptoms were.

The patients then played pingpong once a week for six months. During each weekly five-hour session, they performed stretching exercises followed by table tennis exercises with instruction from an experienced table tennis player.

The program was developed specifically for Parkinson’s disease patients by experienced players from the department of Sports Science of Fukuoka University.

Parkinson’s symptoms were evaluated again after three months and at the end of the study.

The results show that at both three months and six months, study participants experienced significant improvements in speech, handwriting, getting dressed, getting out of bed and walking. For example, at the beginning of the study, it took participants an average of more than two attempts to get out of bed. At the end of the study, it took an average of one attempt to get out of bed.

Study participants also experienced significant improvements in facial expression, posture, rigidity, slowness of movement and hand tremors. For example, for neck muscle rigidity, researchers assessed symptoms and scored each participant on a scale of 0 to 4 with a score of 1 representing minimal rigidity, 2 representing mild rigidity, 3 representing moderate rigidity and 4 representing severe rigidity. The average score for all participants at the start of the study was 3 compared to an average score of 2 at the end of the study.

Two participants experienced side effects; one person developed a backache and another person fell down.

“While this study is small, the results are encouraging because they show pingpong, a relatively inexpensive form of therapy, may improve some symptoms of Parkinson’s disease,” said Inoue. “A much larger study is now being planned to confirm these findings.”

The main limitation of the study was that participants were not compared to a control group of people with Parkinson’s disease who did not play pingpong. Another limitation was that a single specialist assessed the patients.

Article from Psychcentral.com.

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Estrogen Therapy for Men? Maybe.

February 1, 2020 Research

Men are more likely to develop Parkinson’s disease (PD) than women, and the onset of PD in men happens at a younger age. However, women with PD have a higher mortality rate, and once they have Parkinson’s, progression is faster. Research suggests that women get the disease at later in life when compared to men, at least in part, due to the natural protection estrogen provides. There are studies that have demonstrated that hormone replacement therapy (HRT) can provide dopaminergic neuroprotection in both young and menopausal female mice.

Could the female sex hormone, estrogen, be a therapeutic approach for delaying or reducing PD symptoms for men?

Recently published in the Journal of Neuroscience, a study titled, “Female Sex and Brain-Selective Estrogen Benefit α-Synuclein Tetramerization and the PD-like Motor Syndrome in 3K Transgenic Mice” (Rajsombath, Nam, Ericsson, & Nuber, 2019) investigated this possible therapeutic neuroprotective effect.

Using mice called 3K that show motor and neural changes associated with PD, researchers injected male mice under the skin with the hormone therapy DHED. What makes DHED so special is that it was designed to only activate estrogen in the brain. This matters because estrogen therapy has been associated with an increase in cancer in other parts of the human body.

The motor performance and brain health of the 3K male and female mice were compared along with whether DHED affects the progression of PD-like symptoms in males. The motor evaluations included their ability to clasp, climb down a pole, gait (walk) and balance on an accelerating rotarod, which is a lot like lumberjack logrolling. There were also highly sophisticated tests to determine possible changes in the build-up or clearing of protein clumping in the brain, along with the decline or increase in the health of dopamine neurons.

Results

Like the sex differences found in people with PD, 3K male mice developed PD-like symptoms faster than female mice. Furthermore, male mice treated with DHED had:

  • Improved clasping abilities
  • Improved downclimbing
  • Improved gait
  • Improved balance
  • Better clearing of risky alpha-synuclein (protein clumps in the brain)
  • Healthier dopamine neurons

What Does This Mean?

This study focused on the 3K male mice and how they responded to the estrogen therapy, DHED. When the male mice were treated with the DHED, they showed improvements in all the motor functions tested. They also showed significant improvements in the brain, including healthier dopamine neurons and lower amounts of alpha-synuclein at risk for clumping. Remember, clumped alpha-synuclein becomes Lewy Bodies ― a hallmark of PD.

It is also important to note that the successful development of the 3K model itself – which duplicates many differences in male and female PD at motor, cellular and molecular levels – is a significant step forward in closing the gender gap in PD research. Having a model that helps unravel how the pathology differently affects the two sexes informs new avenues of research that could lead to the development of tailored medications and interventions to meet the distinct needs of men and women with PD.

Read the study HERE. This article from parkinson.org.

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Doctors Prescribing Music Therapy

January 1, 2020 Caregivers, Life, Research

Music has proven time and again to be an important component of human culture. From its ceremonial origin to modern medical usage for personal motivation, concentration, and shifting mood, music is a powerful balm for the human soul. Though traditional “music therapy” encompasses a specific set of practices, the broader use of music as a therapeutic tool can be seen nowadays as doctors are found recommending music for a wide variety of conditions.

1. Music Helps Control Blood Pressure and Heart-Related Disorders

According to The Cardiovascular Society of Great Britain, listening to certain music with a repetitive rhythm for least ten seconds can lead to a decrease in blood pressure and a reduced heart rate. Certain classical compositions, if matched with human body’s rhythm, can be therapeutically used to keep the heart under control. The Oxford University study states, “listening to music with a repeated 10-second rhythm coincided with a fall in blood pressure, reducing the heart rate” and thus can be used for overcoming hypertension.

2. Listening and Playing Music Helps Treat Stress and Depression

When it comes to the human brain, music is one of the best medicines. A study at McGill University in Canada revealed that listening to agreeable music encourages the production of beneficial brain chemicals, specifically the “feel good” hormone known as dopamine. Dopamine happens to be an integral part of brain’s pleasure-enhancing system. As a result, music leads to great feeling of joy and bliss.

It’s not only listening to music that has a positive effect on stress and depression. The Namm Foundation has compiled a comprehensive list of benefits of playing music, which includes reducing stress on both the emotional level and the molecular level. Additionally, studies have shown that adults who play music produce higher levels of Human Growth Hormone (HgH), which according to Web MD, is a necessary hormone for regulating body composition, body fluids, muscle and bone growth, sugar and fat metabolism, and possibly heart function.

For more on how music can be composed to benefit the brain, read about States of Consciousness and Brainwave Entrainment.

3. Music Therapy Helps Treat Alzheimer’s Disease

Music therapy has worked wonders on patients suffering from Alzheimer’s disease. With Alzheimer’s, people lose their capacity to have interactions and carry on with interactive communications. According to studies done in partnership with the Alzheimer’s Foundation of America, “When used appropriately, music can shift mood, manage stress-induced agitation, stimulate positive interactions, facilitate cognitive function, and coordinate motor movements.”

4. Studying Music Boosts Academic Achievement in High Schoolers

Early exposure to music increases the plasticity of brain helping to motivate the human brain’s capacity in such a way that it responds readily to learning, changing and growing. “UCLA professor James S. Catterall analyzed the academic achievement of 6,500 low-income students. He found that, by the time these students were in the 10th grade, 41.4% of those who had taken arts courses scored in the top half on standardized tests, contrasted with only 25% of those who had minimal arts experience. The arts students also were better readers and watched less television.” This goes to show that in the formative stages of life, kids who study music do much better in school.

5. Playing Guitar (and Other Instruments) Aids in Treating PTSD

The U.S. Department of Veterans Affairs shared a study in which veterans experiencing Post Traumatic Stress Disorder (PTSD) experienced relief by learning to play guitar. The organization responsible for providing guitars, Guitars For Vets “enhances the lives of ailing and injured military Veterans by providing them free guitars and music instruction.” Playing music for recovery from PTSD resembles traditional music therapy, in which patients are encouraged to make music as part of their healing process. Guitar is not the only instrument that can help PTSD. In fact, Operation We Are Here has an extensive list of Therapeutic Music Opportunities For Military Veterans.

6. Studying Music Boosts Brain Development in Young Children

A research-based study undertaken at the University of Liverpool in the field of neuroscience has light to shed on the beneficial effects of early exposure to music. According to the findings, even half an hour of musical training is sufficient to increase the flow of blood in the brain’s left hemisphere, resulting in higher levels of early childhood development.

The Portland Chamber Orchestra shares, “Playing a musical instrument involves multiple components of the central (brain and spinal cord) and peripheral (nerves outside the brain and spinal cord) nervous systems.  As a musician plays an instrument, motor systems in the brain control both gross and fine movements needed to produce sound.  The sound is processed by auditory circuitry, which in turn can adjust signaling by the motor control centers.  In addition, sensory information from the fingers, hands and arms is sent to the brain for processing.  If the musician is reading music, visual information is sent to the brain for processing and interpreting commands for the motor centers.  And of course, the brain processes emotional responses to the music as well!”

7. Music Education Helps Children Improve Reading Skills

Journal Psychology of Music reports that “Children exposed to a multi-year program of music tuition involving training in increasingly complex rhythmic, tonal, and practical skills display superior cognitive performance in reading skills compared with their non-musically trained peers.” In the initial stages of learning and development, music arouses auditory, emotional, cognitive and visual responses in a child. Music also aids a child’s kinesthetic development. According to the research-supported evidence, a song facilitates language learning far more effectively than speech.

8. Listening To Music Helps Improve Sleep

According to The Center for Cardiovascular Disease in China, listening to music before and during sleep greatly aids people who suffer from chronic sleep disorders. This “music-assisted relaxation” can be used to treat both acute and chronic sleep disorders which include everything from stress and anxiety to insomnia.

9. Playing Didgeridoo Helps Treat Sleep Apnea

 

A study published in the British Medical Journal shows that people suffering from sleep apnea can find relief by practicing the Australian wind-instrument known as the didgeridoo. Patients who played the didgeridoo for an average of 30-minutes per day, 6 days per week, saw significant increases in their quality of sleep and decreases in daytime tiredness after a minimum period of 3-months of practice. Dr. Jordan Stern of BlueSleep says, “The treatment of sleep apnea is quite challenging because there is not a single treatment that works well for every patient. The didgeridoo has been used to treat sleep apnea and it has been shown to be effective in part because of strengthening of the pharyngeal muscles, which means the muscles of the throat, as well as the muscles of the tongue.”

Article from DidgeProject.com.

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Teen Scientist Working on Parkinson’s Treatment

January 1, 2020 Awareness, Change, Research

In North Texas, bright young minds are hard at work and one in particular may be on the verge of shaping the future for patients with Parkinson’s disease.

At 14 years old, it seems there’s nothing Anushka Sridhar hasn’t done.

“Outside of school, I play volleyball, basketball, I’m a third-degree black belt in taekwondo. I do an Indian cultural dance and I’m also part of Destination Imagination,” the Plano ISD 8th grader said.

Sridhar is also a budding scientist, who won the grand prize in her school’s science fair.

She created a device designed to lessen the tremors experienced by Parkinson’s patients.

“My great aunt passed away. With her tremors though, she had a lot of difficulties just with daily activity,” Sridhar said. “So that sparked an idea for me to try and create like a wrist band that could mitigate the tremors.”

For two months, she dove head first into researching Parkinson’s disease, a neurological disorder that causes hand tremors and imbalance.

She learned about how vibration therapy can help the motor skills of Parkinson’s patients.

The idea is the vibrations fool the brain and distract it from the physical sensation of tremors so that patients have an easier time writing.

It’s a well-known theory that even the goliaths of the industry, like Microsoft, are looking into.

Sridhar used common materials, like velcro and simple curcuits to create a prototype wristband. She reached out to the Dallas Area Parkinsonism Society, or DAPS, for test subjects willing to strap on her homemade wristband.

“They were excited that a young person would take that kind iof interest. You can’t help but be impressed when you hear her,” DAPS Executive Director Mike Miles said.

The partnership blossomed, and Sridhar connected with people five times her age. Each one seem impressed with the device, that not only worked, but gave them hope!

“I’m sure she will study that and improve on it and one day, we will have a device that we could put on and write normally,” said 81-year-old Ryan Wagner of Plano.

Sridhar said she planned to expand her research and build more prototypes of her wristband.

She hopes to one day affect the lives of every Parkinson’s patient.

She now advances to the Plano ISD district fair and the Dallas regional science fair.

Article from NBCDFW.

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Why some Parkinson’s patients develop harmful addictive behaviours

January 1, 2020 Education, Life, Research

A QIMR Berghofer study has discovered how the medications given to people with Parkinson’s disease cause some patients to develop addictive behaviours such as problem gambling, binge eating, hypersexuality and excessive shopping.

Medicines that increase dopamine levels in the brain are the cornerstone of treatment for symptoms of Parkinson’s disease. This neurodegenerative disorder damages nerve cells that produce dopamine in the deep structures of the brain.

QIMR Berghofer Medical Research Institute lead researcher and St Andrews Hospital neuropsychiatrist Dr. Phil Mosley said while dopamine replacement therapy was effective for most people diagnosed with Parkinson’s disease, about one in six people treated with the medication developed impulse-control behaviours, such as gambling.

“We found people who developed these addictive behaviours differed in the way their  interacted with dopamine-containing medication, which gave rise to the impulsive behaviour,” Dr. Mosley said.

“None of these people had a history of addictive behaviours before diagnosis and only developed them after they began treatment with dopamine-replacement medications.

“There is currently no way of predicting which individuals are at risk of these terrible side-effects.”

More than 80,000 Australians are living with Parkinson’s disease, with most people diagnosed after the age of 65, although about 20 percent are of working age, according to Parkinson’s Australia.

Dr. Mosley said the study recruited 57 people with Parkinson’s disease from St Andrews War Memorial Hospital in Brisbane, in collaboration with neurologist Professor Peter Silburn.

“We used an advanced method of brain imaging, called diffusion MRI, to reconstruct the connections between different regions of the brain, akin to developing an individualised brain “wiring” diagram for each person in the study,” Dr. Mosley said.

“We asked our participants to gamble in a virtual casino, which gave us a readout of impulsive and risk-taking behaviour in real time.

“By combining data from brain imaging, behaviour in the virtual casino, and the effect of dopamine-replacement medication, we were able to identify people who were susceptible to impulse-control behaviours.

“More broadly, we found a clear link between the strength of the connections in the brain, within circuits that we think are crucial for making decisions and suppressing impulses, and impulsive behaviour, even in people without clinically-significant impulse-control behaviours.”

Dr. Mosley said the study findings indicated that brain imaging and computer-based testing could be used in the future to determine which individuals were at risk of developing these harmful behaviours when treated with dopamine-replacement drugs.

“These disorders are often a second blow to people and their families living with Parkinson’s disease. Some individuals suffer financial problems or relationship breakdowns because of these harmful behaviours,” he said.

“We could offer targeted education to at-risk individuals, or adapt their treatment regimen to minimise the potential harms from these therapies.”

The study’s co-author Professor Michael Breakspear said the findings could also have implications for other psychiatric conditions that are marked by impulsivity, such as ADHD, alcohol and drug addiction.

Article from MedicalXpress.

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Innovative gene therapy trial for Parkinsons disease

November 1, 2019 Education, Research

In people affected by Parkinson’s disease (PD), parts of the brain become progressively damaged over many years resulting in motor symptoms including tremor, rigidity and bradykinesia (slowness of movement).

This deterioration is caused by a loss of dopamine-producing neurons (nerve cells) in an area of the brain called the substantia nigra. In turn, this leads to a reduction in the availability of dopamine, which acts as a neurotransmitter (a chemical released by neurons) to send signals to other neurons, and has a role in controlling movement and balance.

Gene therapy works by introducing genes via an inactivated viral vector (virus) to specific cells providing them with the genetic instructions needed to change their fate.

AXO-Lenti-PD, also known as OXB-102, is a next generation gene therapy and is being tested for the first time by UCL and UCLH researchers at the National Institute for Health Research (NIHR) UCLH Clinical Research Facility, Leonard Wolfson Experimental Neurology Centre, Queen Square.

The therapy has been developed by Oxford BioMedica and Axovant Sciences Ltd for the treatment of PD, and contains three genes that are responsible for producing dopamine, delivered in a lentiviral vector.

Axo-Lenti-PD will be administered into the part of the brain, called the striatum, which is where dopamine is normally released by cells projecting from the substantia nigra. It is a well-defined structure and easily surgically accessible making gene targeting of cells in the striatum a feasible approach with minimal disruption of other brain regions.

The therapeutic rationale for AXO-Lenti-PD treatment of PD is to provide dopamine replacement to the dopamine-depleted striatum of PD patients by gene transfer of the three critical enzymes in the dopamine biosynthesis pathway.

UCLH neurology consultant Professor Thomas Foltynie said: “Genes that increase the production of dopamine could help alleviate the symptoms of Parkinson’s disease, potentially with fewer side effects than traditional drug treatments, by targeting only the areas of the brain that are lacking in dopamine.

“It is envisaged that AXO-Lenti-PD will contribute to a continual supply of dopamine within the striatum and sustain stimulation of post-synaptic dopamine receptors in the absence of disabling side effects that currently complicate dopamine replacement therapy given by oral medication.”

How the trial will work

The trial will assess up to 30 patients with PD from UCLH, the National Hospital for Neurology and Neurosurgery (NHNN), London, Cambridge University Hospital and the Henri Mondor Hospital, Paris.

Patients in Part A of the trial will receive one of three doses of AXO-Lenti-PD, and patients in Part B will receive the optimal dose determined in Part A or an imitation surgical procedure with no treatment.

Patients will have regular assessments after surgery.

The trial’s Chief Investigator is Prof Stéphane Palfi from the Henri Mondor Hospital in Paris.

Professor Foltynie added: “The study will investigate the potential benefit of this treatment to patients with Parkinson’s disease by looking at its impact on symptoms, such as tremor, rigidity, and bradykinesia, and seeing if they improve.

“While we do not yet know if it is effective, it is hoped this therapy will provide patient benefit for many, many years following a single treatment.”

The first patient on the trial was administered the gene therapy by UCL researchers and UCLH clinicians earlier this month, at the National Hospital for Neurology & Neurosurgery, using the NIHR UCLH Clinical Research Facility, Leonard Wolfson Experimental Neurology Centre, Queen Square.

Approval for the multi-centre trial has been sanctioned by the NHS Health Research Authority and follows an earlier study of a first-generation gene therapy called ProSavin®, developed by Oxford BioMedica.

Patient case study

The first patient to be recruited to the trial is a woman in her 50s, who was diagnosed with levodopa-responsive PD more than 10 years ago. She underwent successful surgical treatment to deliver the gene therapy on Wednesday October 17, 2018.

Article from University College London Hospitals.

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Scientists identify early signs of Parkinson’s disease years before symptoms develop

November 1, 2019 Education, Life, Research

Scientists at King’s College London have identified the earliest signs of Parkinson’s disease in the brain up to 20 years before patients present with any symptoms. The findings challenge what had so far been understood about the disease and could lead to new screening tools for identifying high-risk patients and new treatment approaches, although larger studies and more affordable scans would be needed first.

Brain scans of high-risk patients showed a loss of serotonin function before movement disorders developed. The serotonin system regulates mood, sleep and movement.

Parkinson’s is the second most common neurological condition and affects about 145,000 people in the UK. The main symptoms are movement problems such as shaking and tremors, cognitive disorders, depression, and difficulty sleeping, but the disease is known to establish itself in the brain long before symptoms appear and a diagnosis is made.

Studying the early stages of the disease to find treatment approaches with the potential to slow progression represents a huge challenge to researchers, who have so far linked the condition to reduced dopamine levels in the brain. Although no cure for the disease exists, current treatments are focused on controlling symptoms by restoring dopamine levels.

However, the current study shows that changes in the neurotransmitter serotonin occur very early in Parkinson’s disease. These changes could serve as an important early warning signal that a person is at risk.

Serotonin transporter proteins are the first to change in Parkinson’s disease

For the study, Politis and colleagues scanned the brains of 14 people in their 20s and 30s who have a rare genetic disorder that means they are almost certain to develop Parkinson’s once they reach their late forties or fifties.

Parkinson’s disease is characterized by a build-up of the protein α-synuclein in the brain. While the cause of this protein accumulation is usually unclear, genetic mutations are known to cause the problem in a minority of cases.

The subjects, who were all from remote villages in Greece and Italy, have rare autosomal dominant point mutations A53T in the α-synuclein (SNCA) gene. The SNCA mutation originates in villages located in the northern Peloponnese in Greece and is also found in people who moved to nearby areas in Italy.

Half the subjects had already been diagnosed with Parkinson’s, while the other half had not yet displayed any symptoms, making the group perfect for analyzing how the disease progresses.

“Given the known neurochemical changes in the serotonergic system and their association with symptoms of Parkinson’s disease, we hypothesised that carriers of the A53T SNCA mutation might show abnormalities in the serotonergic neurotransmitter system before the diagnosis of Parkinson’s disease, and that this pathology might be associated with measures of Parkinson’s burden,” write the team in the journal Lancet Neurology.

After flying the 14 participants to London for brain imaging and clinical assessment, Politis and team compared the subjects’ data with 65 patients with Parkinson’s disease of a non-genetic cause and 25 healthy individuals.

They found that the people who were destined to develop Parkinson’s had sharply reduced levels of serotonin, which controls many brain functions including mood, cognition, movement, wellbeing and even appetite.

The serotonin system started to malfunction in the subjects with Parkinson’s long before symptoms such as movement problems started to appear and before abnormalities in the dopamine system arose.

“Our findings provide evidence that molecular imaging of serotonin transporters could be used to visualize premotor pathology of Parkinson’s disease in vivo,” writes the team.

Further research ‘could change countless lives’

The brain scans took the form of PET scans, which are difficult to perform and expensive and the researchers say that further work to develop the technique is needed to make the imaging method simpler to carry out and more affordable for use as a screening tool.

Professor of medical imaging at University College London, Derek Hill, says that although the study provides valuable insights, it also has some limitations.

He points out that the results may not scale up to larger studies and that the highly specialised imaging method is limited to a very small number of research centers so could not yet be used to help diagnose patients or evaluate candidate treatments in large studies.

However, the research does suggest that trying to treat Parkinson’s at the earliest possible disease stage is likely to be the best approach to preventing the rising number of people whose lives are destroyed by this hideous disease, says Hill.

Research manager at the charity Parkinson’s UK, Dr Beckie Port, concludes: “Further research is needed to fully understand the importance of this discovery – but if it is able to unlock a tool to measure and monitor how Parkinson’s develops, it could change countless lives.”

Article from News Medical Life Sciences.

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A Wearable Device Is Changing the Way Clinicians Manage PD

November 1, 2019 Education, Life, Research

A recently published study in Functional Neurology suggests that using data from an FDA-cleared watch-like device called the Personal KinetiGraph (PKG) provides an objective and more effective approach to assessing motor fluctuations in patients with Parkinson’s disease (PD) compared with patient-reported motor diaries.

“Motor fluctuations, including ‘wearing-off’ and dyskinesia, are associated with increased disease severity and disability, and PD patients experience decreased quality of life as their response to medical therapy becomes less predictable,” said Echo Tan, MD, a neurologist at Cedars-Sinai Medical Center and lead author on the publication. “Effectively managing motor fluctuations is complicated by the lack of objective assessment tools, leading patients and physicians to rely on direct observation in the clinic or patient reports, which may be unrevealing, incomplete and unreliable. The results of our study demonstrate that the fluctuation score calculated by the PKG system provides objective quantification of motor fluctuations.”

This may help improve the routine management of Parkinson’s patients and enable more objective assessments in clinical trials of Parkinson’s therapies, she said.

Tan told MD+DI the study revealed that the PKG system (developed by Global Kinetics) and the algorithms for calculating a fluctuator score can differentiate between non-dyskinetic and dyskinetic patients. The fluctuator score does not, however, have the sensitivity to detect mild wearing off because no prior study divided patients into more than a binary system. On the plus side, Tan said the PKG also can distinguish between exercise and dyskinesia on the graphical data obtained.

The fact that the fluctuator score was not sensitive enough to detect mild wearing off did come as a surprise to the investigators, but the fluctuator score did show progressively increasing average score range between the four groups, Tan said.

During a BIOMEDevice Boston 2019 panel discussion, Teresa Prego, vice president of marketing and marketing development at the Melbourne, Australia-based company, said the integration of consumer wearables with wearables for chronic disease management has changed the delivery of care and where that care is delivered.

“If I look at the PKG-Watch, for example, in Australia where there are great geographic distances between people with Parkinson’s and a care provider. They are using this remotely,” Prego said. “So you’ll go and see your clinician, have an assessment, but then for the next year, there’s really no need to go into the clinic. You can make care decisions remotely. They’re wearing the vehicles to get that information to the clinician.”

“This implies that it is better at detecting moderate to severe fluctuations,” she said.

Most importantly, the device has changed the way Tan and her colleagues assess and monitor patients with Parkinson’s disease.

“The PKG system can provide additional information about fluctuations that a clinic visit and history can not reveal,” she said. “This is particularly useful for those patients who are not able to provide a good history – such as those with a language barrier or cognitive impairment. It can show true objective levodopa responsiveness, motor fluctuations, daytime somnolence, and medication compliance. “It can be an important triage mechanism for a referral to a movement disorder specialist, or for an advanced surgical therapy referral. It has provided another objective source of information for our clinicians in deciding how to change medical management. Patients also report that the medication reminder function on the device helps them with medication compliance, thereby also enhancing their motor function as well.”

Parkinson’s disease patients typically respond well to medical therapy in the first few years of their disease, but about 40% of the patient population develops fluctuations of response to levodopa and dyskinesia after four to six years of treatment. That percentage jumps to 70% after long-term treatment of nine years or more, according to Global Kinetics. The company said it developed the PKG system to address the lack of objective measurement tools for movement disorders and quantifies the kinematics of Parkinson’s symptoms, including tremor, bradykinesia, and dyskinesia. An algorithm translates the raw data from these assessments into a fluctuation score that can distinguish between patients with motor fluctuations and those without.

The study investigators correlated PKG fluctuator scores (FS) with clinical motor fluctuator profiles in a case-controlled cohort of the study that included 60 patients attending the Movement Disorders Clinic at Cedars-Sinai Medical Center in Los Angeles, CA. Of the 60 patients in the study, six had incomplete data and were excluded from analyses, the company noted.

Here are some key findings from the 54 subjects who completed a six-day PKG trial and completed a standardized motor diary:

  • Based on Wearing Off Questionnaire (WOQ9) and Movement Disorders Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) Part IV scores patients were categorized based on the presence and extent of fluctuations, as follows:
    • Non-fluctuators (NF), N = 14
    • Early fluctuators (EF), N = 15
    • Moderate fluctuators (MF), N = 15
    • Troublesome fluctuators (TF), N = 10
  • The groups varied significantly in terms of disease duration, which was progressively longer with increasing severity of clinical fluctuation and PD dopamine medication measured as levodopa equivalent dose (LED).
  • LED was more than double in patients with troublesome fluctuations compared to those without fluctuations, while patients in the groups including early and moderate fluctuators reported equivalent daily dosages.
  • MDS-UPDRS score increased significantly with the severity of fluctuations, with the highest scores recorded in those with troublesome fluctuations.
  • Patients had a higher tendency to return the PKG than the motor diary (88% vs. 65%).
  • 50% of the patients in the troublesome fluctuator group were excluded due to incorrect diary completion.
  • Compliance with the motor diary improved with decreasing severity of fluctuations.
  • PKG fluctuation score significantly differentiated EF and TF (p = 0.01), as well as dyskinetic and non-dyskinetic subjects (p < 0.005). In contrast, motor diaries could not distinguish the four study groups on the basis of average OFF time, while average time with dyskinesia distinguished NF and MF but did not distinguish among all four groups.
  • PKG identified high levels of dyskinesia in patients who denied having dyskinesia.

The study authors conclude that the data support the use of the PKG fluctuation score as an objective tool for capturing and quantifying motor fluctuations as a mechanism for triaging PD patients. They also note that the PKG transcends language and cognitive barriers and time constraints in the clinic, which are challenges to obtaining accurate patient symptoms to effectively adjust PD treatment.

The main barrier to adoption for products like these is reimbursement, Prego noted.

“Capturing this data and utilizing the advent of these consumer technologies to help manage chronic disease, it’s pretty interesting,” she said. “I think that our traditional ways of reimbursing for medical care have not quite caught up to where the development of consumer wearables has taken us.”

Article from MD+DI.

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Could this newly discovered protein help treat Parkinson’s?

August 1, 2019 Education, Research
Researchers have found a protein that could help reduce the aggregation of toxic proteins in the brain — a hallmark of Parkinson’s disease. But does their discovery offer fresh hope or just “a Band-Aid?”

Does a new discovery reveal a fresh research pathway for Parkinson’s therapy?

The National Institutes of Health estimate that, in the United States, around 50,000 peoplereceive a Parkinson’s disease diagnosis each year.

This widespread condition is characterized by tremors, slowness of movement, and impaired balance and coordination, among other symptoms.

However, its causes remain unknown and treatments only target the symptoms, helping individuals to manage this condition as best they can.

In the brain, Parkinson’s is characterized by a puzzling feature — the aggregation of alpha-synuclein, a protein that becomes toxic and disrupts the neural pathways when it sticks together in large quantities.

This occurs when alpha-synuclein misfolds, that is, when it folds into an incorrect shape that does not allow it to function correctly, which may cause or facilitate disease.

Alpha-synuclein is typically present at high levels in the brain, and it is also present in other tissue in smaller amounts. Still, researchers have no idea what role this protein usually plays in maintaining neural health or how to prevent it from misfolding.

But a new study, from Purdue University, in West Lafayette, IN, has identified a protein able to reduce the aggregation of misfolded alpha-synuclein. The findings feature in the Journal of Molecular Biology.

How HYPE may reduce aggregation

The new research has focused on the therapeutic potential of a protein called “HYPE,” which, the investigators explain, is the only Fic protein present in humans.

Fic proteins help decide whether a cell survives or dies when it encounters stress, characterized by the misfolding of the cell’s proteins.

“Since HYPE plays such an important role in how cells deal with stress from misfolded proteins, we wondered whether diseases that result from protein misfolding were likely to need HYPE,” explains lead study author Seema Mattoo, Ph.D., an assistant professor of biological sciences at Purdue.

She continues: “We know that in Parkinson’s disease, often the misfolded protein is [alpha-synuclein]. So we asked if HYPE could modify [alpha-synuclein], and if so, what are the consequences?”

In the current study — which the researchers conducted in vitro, using cell cultures in a laboratory setting — they found that HYPE can indeed act on alpha-synuclein, decreasing the amount of aggregation of misfolded proteins. The researchers call this process “AMPylation.”

Then, the team wanted to see if AMPylation actually showed any promise as a potential therapeutic process. In Parkinson’s disease, aggregated, misfolded proteins can puncture the membranes of neurons (brain cells), disrupting their functioning.

Mattoo and colleagues wanted to find out whether AMPylation would also lead to fewer holes in the membranes of cells. To do so, they used a combination of lipids to create a surface simulating that of cell membranes.

They also added dye to the lipids, so if alpha-synuclein aggregates punctured them, the action would become visible through leaked dye.

After doing so, Mattoo notes, “We found that less dye was released with the modified [alpha-synuclein], meaning the membrane stayed more intact.”

“That means HYPE could possibly have a therapeutic effect on Parkinson’s disease,” she adds. Moreover, as Mattoo and colleagues note in their study paper, “This is the first report identifying [alpha-synuclein] as a target for HYPE.”

Going beyond the ‘Band-Aid?’

In a final experiment, Mattoo and the team studied HYPE-modified alpha-synuclein using an electron microscope. This allowed them to observe that, after interacting with HYPE, alpha-synuclein’s structure had changed.

Under regular circumstances, the researchers note, alpha-synuclein twists, which may explain its potential to form aggregates. However, when modified by HYPE, the protein tended to twist less, instead forming parallel strands.

This new modification, the researchers argue, may prevent alpha-synuclein from aggregating as much.

While the current research shows promise in finding new therapies for Parkinson’s disease, the study authors explain that they still have a long way to go.

“We’re in the early stages [of this research],” Mattoo admits, “but these results are giving us a new angle to look at potential therapeutics.”

“We’re trying to come up with drugs that could be used to manipulate HYPE’s activity. You could give them to patients who are starting to show signs of Parkinson’s or who are prone to having aggregated [alpha-synuclein]. That’s the direction we want to go [in],” the researcher explains.

Article from Medical News Today.

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