science

Spinal Cord Stimulation as PD therapy

May 1, 2021 Research

A new study finds that spinal cord stimulation could represent an alternate therapy for people with Parkinson’s disease that is resistant to conventional treatments. The researchers claim that this emerging technology may help decrease pain and improve mobility.

Close to 1 million people may be living with Parkinson’s disease in the United States. This long-term degenerative disorder results from damage to nerve cells in the brain that produce dopamine.

As the symptoms of Parkinson’s develop, a person may first experience a tremor in one hand and stiffness elsewhere in the body. The four key symptoms are:

a tremor
stiffness or tightness in the arms, legs, or elsewhere in the body
slowed movement and difficulty initiating and coordinating movement — possibly presenting as a loss of facial expression or a slow, stuttering walk
difficulty with fine movements, such as doing up buttons

Ultimately, a person experiences problems maintaining balance, and some people with Parkinson’s also develop dementia. Certain people only develop motor symptoms and others have cognitive symptoms, and doctors are still unsure why this is.

Some people refer to dopamine as the “feel-good” hormone or chemical messenger. It has various roles, including in movement coordination, and it is an active player in the brain’s reward system.

Most people with Parkinson’s also develop at least one nonmotor symptom. The most common of these are sleep disturbances, a loss of smell, pain, constipation, and excessive sweating.

People may also experience anxiety and neuropsychiatric symptoms, such as depression, apathy, or psychosis.

This wide array of symptoms can affect relationships and cause people with Parkinson’s to have lower self-worth and lose their sense of identity.

While the cause of Parkinson’s remains unknown, prescription treatments for dopamine deficiency and deep brain stimulation (DBS) are the gold-standard approaches.

But dopamine treatment can cause side effects, such as dyskinesias, involuntary twisting movements of the body. These usually diminish as the drug wears off. Other adverse effects include gastrointestinal disturbances, hallucinations, anxiety, and muscle fatigue.

Meanwhile, DBS can cause brain bleeding, infection, and seizures.

Given the urgent need for treatments that alleviate Parkinson’s symptoms with minimal risks, a group of researchers has now investigated an alternate approach: spinal cord stimulation. They have published their findings in the journal Bioelectronic Medicine.

Assessing an alternate therapy

The researchers set out to determine whether spinal cord stimulation could be a singular therapy for Parkinson’s disease and a salvage therapy, in people for whom DBS is increasingly ineffective.

The study included 15 participants, with a mean age of 74 years. On average, they had received the diagnosis of Parkinson’s disease 17 years earlier.

Eight had undergone DBS previously, and the others had only received medication, including pain relievers, as Parkinson’s treatment.

All experienced chronic pain that was resistant to pain relief medication and changes in their treatment for the disease. When a particular nerve was involved, drugs called nerve blocks had been ineffective.

Once the study had begun, electrodes were surgically implanted under the participants’ skin near their spines.

The participants could choose to receive mild electric currents in three stimulation modes: continuous tonic stimulation, continuous burst stimulation, or a cycling mode with burst stimulation, which provided stimulation for 10–15 seconds at a time, separated by pauses of 15–30 seconds.

The researchers observed that the 15 patients experienced “significant improvement” after using the spinal cord stimulator device.

Based on the visual analog scale of pain intensity — the seven patients who had never received DBS experienced a 57% reduction, on average. For those who had received DBS in the past, the average reduction in pain intensity was 61%.

In addition, the researchers found that participants who opted for the cycling mode experienced, on average, a 67% reduction pain, using the same scale. By comparison, those who chose continuous burst stimulation had, on average, a 48% reduction in their pain scores.

Of the 15 patients, 11 had been able to complete a 10-meter walk before and after the study. After the stimulation, eight people (73%) in this group showed an average improvement of 12% during their 10-meter walks. The researchers used these walks to assess the participants’ mobility and gait.

They also used a “timed up-and-go” test to measure how long it takes a person to get up from a chair, walk 3 meters, turn around, walk back to the chair, and sit down. Among the 11 participants who completed this test, seven (64%) showed improvement in their completion times.

The patients who chose a continuous burst pattern had an 18% improvement in their timed up-and-go scores. However, those who chose the cycling mode had a 7% worsening in these scores.

While many of the results seem promising, it is important to note that spinal cord stimulation carries some risks and may cause complications, including bleeding at the site of insertion.

The researchers also acknowledge that their study design had a limitation: They were unable to determine whether the improvements in scores stemmed from the stimulation itself or the resulting decrease in pain, which allowed for more mobility.

The team of researchers, based in the U.S. and Japan, observe:

“Spinal cord stimulation is an emerging technology that can potentially be utilized to treat both the motor and nonmotor symptoms, such as pain, that patients with Parkinson’s disease deal with on a daily basis.”

Another limitation involved the fact that the patients did not receive the spinal cord stimulators in the exact same location, due to differences in how their pain presented. Also, not every patient was able to return and complete the mobility tests, which reduced the already small sample size.

In addition, this small study did not include a control group, so some changes in pain scores could result from a placebo effect.

This research should thus be regarded as a proof-of-concept study. Further evaluation in larger trials is needed.

Finally, some researchers involved in this study have disclosed potential conflicts of interests due to affiliations with medical device companies and pharmaceutical companies, including Medtronic, Abbott, Boston Scientific, Kyowa Kirin, Boehringer Ingelheim, AbbVie, and FP Pharmaceutical.

Article from Medical News Today.

Coronavirus and treatment for Parkinson’s

July 1, 2020 Awareness, Education, Life

What do we know about the relationship between coronavirus and Parkinson’s?

Joaquim Ferreira, neurologist, Portugal: There is still scarce information regarding many clinical aspects of this infection and its potential short- and long-term complications. We know that the majority of people with Parkinson’s are elderly, and age is a risk factor for the more severe forms of Covid-19. On the other hand, we recognise that patients might be affected indirectly by the lockdown physical restrictions, the psychological impacts and the compromised healthcare.

Miriam Parry, senior Parkinson’s Disease nurse specialist, UK: We do know that people with Parkinson’s are more prone to pneumonia and infections. Parkinson’s can cause respiratory issues for some people – if you have lived with Parkinson’s for a long time, you are more likely to have breathing and respiratory difficulties. This is why people with Parkinson’s are described as being at greater risk of severe illness if they get coronavirus. As such, their caregivers need to take precautions.

Rick Helmich, neurologist, the Netherlands: We know very little, but knowledge is rapidly increasing. Parkinson patients who develop Covid-19 seem to suffer from the same symptoms as other people and to approximately the same degree. However, patients who get sick from coronavirus may suffer from a worsening of their Parkinson symptoms. This is a well-known finding that also occurs when Parkinson patients develop other non-coronavirus infections. The current pandemic also has effects on Parkinson patients that are not so visible, such as increased stress levels and less physical exercise due to the social isolation measures.

How has the coronavirus crisis affected how you and your colleagues carry out your roles, and interact with patients?

Emma Edwards, Parkinson’s specialist nurse, UK: The coronavirus crisis has meant that our face-to-face appointments were stopped with immediate effect. We knew that telehealth technology was due to be implemented in our work area over a planned period of about seven months. When the crisis happened, that roll out took about seven days! In May, I started to see some patients again in their homes. Those allocated for this type of review were people that were running into problems with their Parkinson’s that we couldn’t resolve over the phone or via the virtual clinics.

Helmich: For a few months, I have been working mainly from home, and all my contacts with patients were through video-conferencing and by phone. It took some time to adjust, but I am actually very happy with how it turned out now. It is amazing how much you can see and discuss via a good video connection. On the other hand, more subtle things are better seen in real life, so I am happy that we are allowed to see more patients at our hospital in the next weeks.

Ferreira: The major implications of visit cancellations for patients that were hospitalised, or doing rehabilitation programmes as inpatients, should also be mentioned. This situation forced all health professionals to be involved in facilitating communication and minimising the consequences of not seeing family and friends.

How has the coronavirus crisis affected access to treatment for people with Parkinson’s?

Helmich: This is a topic that many patients are worried about: access to health care. Many Parkinson patients are treated by a whole team of professionals, including a neurologist, a Parkinson nurse, a physical therapist, and sometimes a psychiatrist, speech therapist, or occupational therapist. Access to these health care providers has been restricted by the isolation and social distancing measures. Not all people have good access to internet, and not all treatments can be given through video conferencing. So, I believe that the care for Parkinson patients has certainly suffered from the coronavirus pandemic.

Ferreira: The coronavirus pandemic severely affected the follow-up of people with Parkinson’s disease. The regular consultations were cancelled, making it more difficult or impossible the access to physicians and other health professionals. Pharmacological prescriptions were more difficult to obtain. Sessions of physiotherapy, speech therapy and other therapeutic interventions were cancelled, and physical activity and exercise was highly reduced for many patients. Many deep brain surgeries were deferred, and patients included in research studies and clinical trials saw their consultations being moved to phone contacts or videocalls.

Edwards: Face-to-face sessions such as our Parkinson’s exercise groups, have also been postponed but luckily the staff that ran those groups produced a brilliant DVD of the common exercises they undertook in class. These were distributed out to homes at the beginning of the outbreak and were warmly received by many people with Parkinson’s.

What actions should people with Parkinson’s take at the moment?

Ferreira: The most important recommendation for people with Parkinson’s and their close friends and family is to follow the general public health recommendations that apply to the elderly population. At the current stage of the pandemic, when governments are lowering the confinement measures, the most important message is to alert everybody that this pandemic is not over and the general measures that are being recommended for the general population should be followed strictly in the next months.

Parry: When you leave the house, for any reason, you should avoid busy spaces and keep a distance of around two meters from people you do not live with, while wearing a face mask. You should also continue to follow good hygiene practices, including handwashing, not sharing crockery and cutlery, wiping down surfaces, and not entering other people’s homes. You can ask your local pharmacist to deliver medication to your home address or ask family members or friends to help.

Edwards: I would really advocate for people, if they can, to exercise. It has proven benefits not just for physical health in Parkinson’s but for promoting good mental health. I’ve been really impressed with the exercise classes available online to people with Parkinson’s whilst the group classes have been postponed.

What should people with Parkinson’s do if they have hospital and GP appointments during this period?

Parry: If you’re in the UK, please call the GP’s practice and ask for further information and direction pending the reasons for the appointments. The GP practice will be able to advice you whether it is urgent or offer you a phone or video consultation. Routine hospital appointments have now changed to virtual clinics using phone and video link consultations.

Ferreira: During this crisis, health institutions in Portugal have changed their procedures in order to implement safety circuits for those who will need to attend their routine visits or need to go to the hospital in an urgent situation.

Edwards: I would imagine as we come out of the lockdown, clinical outpatient appointments in the UK will look very different to what people are used to. Certainly, in our area, personal protective equipment will be worn by staff and visiting patients are encouraged to wear face masks. If people with Parkinson’s need advice on managing their condition and are not sure when their next review will be, they should contact their local Parkinson’s service and ask for help. Be proactive!

How can people with Parkinson’s look after their mental wellbeing?

Ferreira: All health professionals that follow patients with Parkinson’s recognise that this has been a difficult time, not just for the patients but for all around them. The most important thing for the community is strengthening support and continuing care, keeping the links between patients, their families, caregivers and health professionals.

Helmich: This is different for everyone. Some of my patients even like certain aspects about the current situation, such as a reduction in workload, deadlines, or social obligations. In general, I think it is good to try to stay in touch with your loved ones. Find a new structure for your day that works for you and develop new exercise routines. There are many online events available for Parkinson patients, such as online dancing or singing classes. So, it might be worthwhile to have a look online to see what is out there or ask someone to help you do so. Don’t be afraid to speak about your worries or fears.

Edwards: Being able to connect with others has been a challenge during the lockdown, but as restrictions are eased, I really encourage people to meet others again, albeit in a safe way. For many during coronavirus, that has been via online forums like Zoom or having a socially distanced chat over the garden fence to family and friends. I’m also a massive advocate for mindfulness. It’s a way to be fully present, having an awareness of where we are and what we are doing and feeling, without being overwhelmed by what’s going on around us.

Parry: It is normal and expected to feel a range of emotions during this pandemic including fear, increased anxiety, anger and sadness. There is guidance on looking after mental wellbeing during this time from mental health charity Mind, as well as support on the Parkinson’s UK and Parkinson’s Foundation websites.

What is the advice for those living with a vulnerable person?

Parry: Visitors and people who provide care for those with Parkinson’s should protect them and reduce their risk by staying at home as much as possible. They should work from home, if they can, and limit contact with other people.

Ferreira: It is a good principle to assume that everybody who we are in contact with may be infected, even if they don’t present any suspected symptoms. No one can be sure that they are not infected or do not have a risk of infecting others. This is even more relevant for health professionals, caregivers, family members and those that have close contact with vulnerable populations.

Edwards: I knew from the moment I re-started my home visits that I had not fully been picking up the impact that the coronavirus and subsequent lockdown has had on care partners. It was harder to pick up the subtleties of care partner stress on the telephone or even on the telemedicine appointments. I’m certainly more mindful that we need to continue to address this area as digital medicine becomes more accessible for people with Parkinson’s and potentially less contact is had with partners or carers during these interactions.

Helmich: Be aware that vulnerable people are sometimes less able to cope with new or threatening situations. Be patient if your loved ones are anxious, worried, or experience a worsening of their symptoms.

Do you think the coronavirus crisis will have a long-term impact on people with Parkinson’s?

Ferreira: The limitations induced by the Covid-19 pandemic are here to stay and we need to be prepared to adapt for the next months.

Parry: The Covid-19 pandemic could potentially have a long-term impact on the physical and mental health of people with Parkinson’s, and many studies are currently taking place looking at the effect of this pandemic.

Edwards: I think lots of clinicians were hoping that we could eventually use technology in how we review our patients, and this crisis has pushed that to the forefront. I like being able to offer our patients a wider range of ways that they can access information and advice – from virtual clinics to wearing digital technology – but also being able to offer more traditional face-to-face home visits if needed.

Need to know

Emma Edwards: I’m a mental health nurse in the UK – however for the last 10 years I’ve worked as a Parkinson’s specialist nurse in the community. I had worked in a large rural area for many years, but more recently have moved to a post in a city. Due to the lockdown on clinical work environments, my dining room is currently my office!

Joaquim Ferreira: I am a neurologist mainly working in the field of Parkinson disease for the past 25 years. I am also professor of neurology and clinical pharmacology at the University of Lisbon, Portugal. More recently, I founded CNS, Campus Neurológico Sénior, which is a movement disorders centre focused on the multidisciplinary care and rehabilitation for Parkinson’s patients.

Miriam Parry: I work as senior Parkinson’s Disease nurse specialist (PDNS) at King’s College Hospital NHS, Parkinson’s Foundation Centre of Excellence in London, UK. My role is to provide a holistic approach to care and seamless service to people with Parkinson’s and their family and carers, providing ongoing support, educating and empowering patients to become experts in their condition. Above all, I aim to engage people with Parkinson’s with King’s rich research portfolio on offer, as without it we would not have the knowledge and the care pathways that we do.

Rick Helmich: I live in Nijmegen, the Netherlands and work as a neurologist and neuroscientist at the Radboud University Medical Centre. I specialise in Parkinson’s, and in my research at the Donders Institute, I use brain imaging to help understand symptoms and phenomena I see in my patients. Lately I’m intrigued by the effects of stress on patients with Parkinson’s, both the causes and the consequences.

Information from Parkinsonlife.eu.

“You’re superhuman up there”: Parkinson’s in space

July 1, 2020 Life

Journeying into space is an incredible feat – it’s even more impressive when you’ve been diagnosed with Parkinson’s.

Michael ‘Rich’ Clifford found out he had the condition in 1994. Two years later he undertook his third journey into space on the US Atlantis shuttle.

In webcast conversation with Dr Ray Dorsey, co-author of Ending Parkinson’s Disease: A Prescription for Action, the former astronaut outlined his experience working with US space agency NASA, spoke about his exposure to pesticides – and shared what his symptoms were like in space.

“It was an easy decision to fly”
“When I got diagnosed with Parkinson’s I thought it was over and NASA asked me what I wanted to do,” Clifford told Dorsey. “I said, ‘You mean it’s up to me?’ and they said, ‘Yeah, we consider you still qualified for flight.’ I said, ‘Well, I’ll go fly again.’ And it was as easy as that.”

“It was special, because I’d done a lot of preparatory work on that – all the EVA [Extra-Vehicular Activity] simulations and validation of the positions and equipment we were going to use – so it was an easy decision to fly.”

Asked if he noticed his Parkinson’s symptoms during the seven-day period in space, Clifford said: “I felt my right-hand tremor one time, but it was very mild… I think it showed more in space. I could feel it more. When we re-entered for landing, I noticed with the pull of g-forces, my hands would go down, and it was much easier to work with.”

Lifting heavy equipment, weighing over 150 pounds, was significantly easier: “I could have just dragged it along with my fingernails – it was neat. You’re superhuman up there.”

Parkinson’s and pesticides
Growing up in Utah, US, Clifford had no family history of Parkinson’s. However, he told Dorsey, he was exposed to pesticides through a high-school job cutting grass and while working as a private pilot: “I didn’t know it was dangerous. I didn’t like the way it smelled, but it was just a job.”

Then, working as a gas station attendant Clifford encountered trichloroethylene (TCE) – another substance that has been linked with Parkinson’s.

“In the shop we would get grease spills all the way and would clean it up. I didn’t realise there was a nasty chemical in it, but it was efficient for cleaning up the grease. I did that for about three years.”

“We should be getting rid of these chemicals,” he told Dorsey, who has written about the impact of pesticides in his book. “It’s going to take somebody pushing it, like you are, to get this done.”

“Just because you have Parkinson’s, you don’t have to give up”
When he was first diagnosed, Clifford didn’t tell the rest of his crew that he had the condition. However, he decided to announce it publicly in 2011 – 17 years after his diagnosis – to “get the issue out on the table”.

“I thought it was time to reveal it. I felt it was a good thing for the community for me to announce I had Parkinson’s,” he said.

He was then encouraged by his doctor, whose son was a film producer, to share his story in a movie. ‘The Astronaut’s Secret’, a documentary released in 2014, covers Rich’s experience working with NASA while living with the condition.

Rich hopes his story inspires others with the condition: “Just because you have Parkinson’s, you don’t have to give up.”

Article from Parkinsonslife.EU.

Phlegm-busting Drug Ambroxol Shows Promise in Parkinson’s

March 1, 2020 Research

One of the major genetic risk factors believed to contribute to the development of Parkinson’s disease (PD) is having a mutation in the gene called GBA1 (glucocerebrosidase). Unable to do its job correctly, this damaged gene leads to the build-up of unhealthy, misfolded clumps of alpha-synuclein in the brain. These clumps, called Lewy bodies, impact dopamine production and are the hallmark of PD. What if there was a way to prevent the build-up of Lewy bodies in the first place?

A 2020 study published in JAMA Neurology, titled, “Ambroxol for the Treatment of Patients with Parkinson Disease with and Without Glucocerebrosidase Gene Mutations: A Nonrandomized, Noncontrolled Trial” (Mullin et al., 2020), investigated whether an over-the-counter cough syrup, called Ambroxol, may be the key. The cough syrup, specifically, an expectorant, is used to break up phlegm.

This 186-day clinical trial of 17 people with PD ― with and without the GBA1 mutation ― involved participants taking progressively increasing doses of Ambroxol in the form of an oral tablet. Baseline measurements included physical and neurological examination, an electrocardiogram, blood sampling and spinal fluid examination obtained by lumbar puncture. Three additional in-person clinical visits were held on day 11, day 93, and day 186. Of note, at baseline, Ambroxol was undetectable in both the blood serum and spinal fluid. All study participants continued their normal L-dopa therapy throughout the trial.

Results
In study participants both with and without the gene mutation:

Ambroxol successfully crossed the blood-brain barrier.
Ambroxol was safe and well-tolerated at the administered dose.
Ambroxol successfully bound to the mutated genes’ protein, which physically helped the protein function properly.
Healthy levels of alpha-synuclein increased in the spinal fluid.

What Does This Mean?
This study showed that Ambroxol is safe to use as a treatment in people with Parkinson’s. Ambroxol may slow the progression of Parkinson’s disease. How? Taking Ambroxol as a medication can prevent the negative effects of the GBA mutation ― including possibly reducing the formation Lewy bodies at the source. Ambroxol shows promise, and warrants further investigation ― including conducting larger, placebo-controlled trials.

Of note, while Ambroxol has been used as a safe and effective over the counter expectorant for adults and children in more than 50 countries for 30-plus years, the administered dose in this trial was approximately 10 times the specified dosage. Additionally, Ambroxol is currently not approved for prescription or over the counter use by the U.S. Food and Drug Administration (FDA) for any indication, at this time.

Article from Parkinson.org.

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.

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.

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.

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.

Parkinson’s differences in women and men

October 1, 2019 Change, Education, Life

There is growing evidence that Parkinson’s disease (PD) affects women and men differently. In this insightful review, published in the Journal of Parkinson’s Disease, scientists present the most recent knowledge about these sex-related differences and highlight the significance of estrogens, which play an important role in the sex differences in PD.

PD is a slowly progressive disorder that affects movement, muscle control, and balance. It is the second most common age-related, neurodegenerative disorder, affecting about 3% of the population by the age of 65 and up to 5% of individuals over 85 years of age. The risk of developing PD is twice as high in men than women, but women experience a more rapid disease progression and a lower survival rate.

“It is becoming increasingly evident that PD differs in women and men,” explained lead author Fabio Blandini, MD, Scientific Director of the IRCCS Mondino Foundation, National Institute of Neurology, Pavia, Italy. “Recent research findings suggest that biological sex also impacts on disease risk factors and, potentially, on molecular mechanisms involved in the pathogenesis of PD.”

This review meticulously examines the most recent knowledge concerning differences between women and men with PD including:

Motor and non-motor symptoms
Quality of life
Genetic and environmental risk factors
Pharmacological therapy of motor and non-motor symptoms
Surgical procedures
PD and steroids
Impact of biological sex on pathophysiology

Recent research has shown that women and men have distinctive motor and non-motor symptoms as their PD progresses. Motor symptoms emerge later in women: tremor is a common first presenting symptom associated with recurrent falls and more severe pain syndromes with specific characteristics such as reduced rigidity, a higher propensity to develop postural instability, and elevated risk for levodopa-related motor complications. Conversely, male PD patients show more serious postural problems and have worse general cognitive abilities: freezing of gait—the most disabling motor complication of PD—develops later in men; however, men have a higher risk of developing camptocormia (abnormal severe forward flexion of the trunk when standing or walking). An ongoing clinical trial is evaluating the prevalence in PD and the biological sex impact on other postural abnormalities, such as Pisa syndrome (a reversible lateral bending of the trunk with a tendency to lean to one side), antecollis (dystonia of the neck resulting in excessive forward flexion), scoliosis (a sideways curvature of the spine), and deformities related to hands and/or toes.

Non-motor symptoms have been the subject of a study of over 950 PD patients, which concluded that symptoms such as fatigue, depression, restless legs, constipation, pain, loss of taste or smell, weight change and excessive sweating are more common and severe in women. Other studies have demonstrated that male PD patients have worse general cognitive abilities and male sex is the primary predictive factor for mild cognitive impairment and its more rapid progression in the severe stage of the disease. A diagnosis of PD with dementia has a greater impact on life expectancy of women than men; in addition, women show distinctive symptoms as well as differences in the response to pharmacological therapies and deep brain stimulation, and in their personal evaluation of the quality of life compared to men.

The authors note that the distinctive clinical features as well as the contribution of different risk factors support the idea that PD development might involve distinct pathogenetic mechanisms (or the same mechanism but in a different way) in women and men. They highlight the significance of estrogens, which play an important role in the sex differences in PD, providing disease protection as demonstrated by the similar incidence of the disease in men and post-menopausal women.

“Sex hormones act throughout the entire brain of both males and females and sex differences are now highlighted in brain regions and functions not previously considered as subjected to such differences, opening the way to a better understanding of sex-related behavior and functions,” added Silvia Cerri, Ph.D., head of the Laboratory of Cellular and Molecular Neurobiology of the IRCCS Mondino Foundation and first author of the article. She commented: “Neuroinflammation is an important piece of the pathogenic puzzle of PD. Current evidence suggests that the physiological role exerted by microglial and astrocytic cells could become compromised during aging, thus contributing to PD onset and progression. Since estrogens have anti-inflammatory properties, their actions throughout the lifespan could partially account for sex-related risk and manifestation of PD.”

By drawing attention to sex-related differences and disparities in PD, Dr. Blandini and colleagues hope this will further encourage the scientific community and policy makers to foster the development of tailored interventions and the design of innovative programs—for example in care practices—that meet the distinct requirements of women and men with PD. “Women diagnosed with PD are a sizable portion of the PD population, but their specific needs are still partially overlooked. The differences between women and men strongly suggest the need for a personalized (sex-related) therapy in PD,” concluded Dr. Blandini and Dr. Cerri.

Article from MedicalXpress.

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.

What do we know about the relationship between coronavirus and Parkinson’s?

How has the coronavirus crisis affected how you and your colleagues carry out your roles, and interact with patients?

How has the coronavirus crisis affected access to treatment for people with Parkinson’s?

What actions should people with Parkinson’s take at the moment?

What should people with Parkinson’s do if they have hospital and GP appointments during this period?

How can people with Parkinson’s look after their mental wellbeing?

What is the advice for those living with a vulnerable person?

Do you think the coronavirus crisis will have a long-term impact on people with Parkinson’s?

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

2. Listening and Playing Music Helps Treat Stress and Depression

3. Music Therapy Helps Treat Alzheimer’s Disease

4. Studying Music Boosts Academic Achievement in High Schoolers

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

6. Studying Music Boosts Brain Development in Young Children

7. Music Education Helps Children Improve Reading Skills

8. Listening To Music Helps Improve Sleep

9. Playing Didgeridoo Helps Treat Sleep Apnea

How HYPE may reduce aggregation

Going beyond the ‘Band-Aid?’

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