Making Meaning of It All

well-being

Wellness map in hand, I pass through the fog of conflict that is my life and agree to enter sanctuary. I surrender myself to experiences of bliss and well-being.

Caressed by calmness, the fog has lifted. Like a crisp fall day, the colors are vibrant and the view breathtaking. In the distance is something not seen before. This is the destination toward which I must strive. It beckons to me, constantly whispering in my ear, “Come to me and discover what you need.”

It’s all making sense.

Our brains are wired to make connections. Not just neural ones, but associative ones. When we have a new experience, we associate it with memories of similar events. The further the new experience is from the known, the more difficult the association.

An experience that supports our well-being can be so different from any in our history that an association is difficult. It is so difficult that we procrastinate. “I can’t make sense of this, so I’m not going to do anything about it until I can.” It’s a cautious approach I’ve taken many times in my life. Eventually, I get splinters from sitting on the fence too long.

Greek philosopher Epicurus believed that happiness comprises friendship, freedom from everyday life and politics, and time and space to think things through. Epicurus would not advise spending money as temporary relief for a bad day. He would suggest taking time to reflect and contemplate.

Socrates had a different stance, as evidenced by his dictum: “The unexamined life is not worth living.” Socrates believed you should review and examine every aspect of your life to get the best out of it. A life bereft of meaning and purpose lacks action guided by that purpose. Meaning and purpose are part of a healthy self-concept.

Making sense of a well-being moment can be challenging. They are often scarce, and we have little experience with them. But well-being moments always come with useful information. Without that, they are just “feel-good” moments.

Taking that information and turning it into wisdom for a lifetime requires wrestling with it, using it, and integrating it into life — use it or lose it. It helps to have an experienced guide. Teachers of mystic traditions suggest mentoring in a sanctuary as one way to assist in the meaning-making process.

How we make sense of everything is vital to our movement forward, against the challenges, the setbacks, and the frailty that we encounter. Making sense of it gives us meaning and purpose throughout our journey with Parkinson’s disease, and the rest of our lives.

***

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

The post Making Meaning of It All appeared first on Parkinson’s News Today.

Parkinson’s Foundation Opens Campaign to Support Newly Diagnosed

Parkinson's Foundation program

To provide new patients with the information, tools and resources they need to best manage their health, the Parkinson’s Foundation has launched a campaign to close the gap between learning of an illness and knowing how and where to find help.

Called “Newly Diagnosed: Building a Better Life with Parkinson’s Disease,” the effort is said to be the first such national campaign designed to reach the 60,000 people in the U.S. estimated to be diagnosed with Parkinson’s (PD) every year.

“In an effort to help provide better outcomes from the beginning of their journey, the Parkinson’s Foundation is whole-heartedly committed to connecting sooner with those facing a life-changing diagnosis,” John L. Lehr, the foundation’s president and CEO, said in a news release. “Our goal is to empower everyone new to our community to build a better life with Parkinson’s from day one while addressing their unmet needs.”

The organization surveyed more than 1,100 PD patients in January to better understand the needs and priorities of the newly diagnosed. Results showed that 42 percent of patients and 45 percent of their care partners had received no educational materials about Parkinson’s within six months of diagnosis.

Those findings led to the campaign, which seeks to not only connect with new patients early, but to provide ongoing support. The effort will include a free Newly Diagnosed Kit that may be ordered or downloaded, educational programs focused on care and research, funding for community grants that help the newly diagnosed, relevant podcasts, and an online community to be launched later this year aimed at establishing peer-to-peer connections.

“Early in my diagnosis with Young Onset Parkinson’s, I realized that I couldn’t find all of the answers I was looking for,” said Christina Korines, who was diagnosed at 33. “I needed a partner to help me navigate my diagnosis, and the Parkinson’s Foundation is the go-to partner for anyone diagnosed with Parkinson’s, especially the newly diagnosed.”

The organization now offers has a video and other information for new patients, including Five Steps to Living Well. More information is also available by calling the Parkinson’s Foundation Helpline at 800-4PD-INFO.

Parkinson’s disease affects nearly 1 million U.S. residents and nearly 10 million people globally. After Alzheimer’s, it’s the second most common neurodegenerative disorder in the U.S.

The post Parkinson’s Foundation Opens Campaign to Support Newly Diagnosed appeared first on Parkinson’s News Today.

Stool Calprotectin May Be Used as Marker of Bowel Inflammation in Parkinson’s Patients, Study Finds

calprotectin

The levels of calprotectin — a protein whose levels increase in response to tissue inflammation — in the stool may be used as a marker of bowel inflammation in patients with Parkinson’s disease, according to a recent study.

The results, “Fecal Calprotectin as a Marker of the Gut Immune System Activation Is Elevated in Parkinson’s Disease,” were published in Frontiers in Neuroscience.

A hallmark feature of Parkinson’s is the progressive degeneration of brain cells due to the accumulation of toxic clumps of alpha-synuclein, called Lewy bodies.

Some scientists believe Lewy bodies form in the enteric nervous system (ENS) — the network of nerves that innervate the gastrointestinal (GI) tract — then spread to the brain, where they gradually damage and destroy brain cells.

It also is thought that lesions in the ENS may be linked to bowel inflammation, dysmotility (impairment of GI tract muscles) and high intestinal permeability, all of which contribute to gastrointestinal symptoms of Parkinson’s disease, such as constipation.

In this study, researchers from Wrocław Medical University in Poland set out to explore the usefulness of calprotectin and zonulin — two proteins whose levels tend to increase in the presence of inflammation and immune system dysfunction — as markers of bowel inflammation and impaired intestinal permeability in patients with Parkinson’s disease.

To that end, they gathered stool samples from 35 patients with Parkinson’s disease who were either hospitalized or routinely followed at the Department of Neurology at Wrocław Medical University, and 20 healthy individuals (controls).

The levels of calprotectin and zonulin in the stool were measured by Enzyme-Linked Immunosorbent Assay (ELISA), a technique that allows researchers to measure the amount of a specific protein of interest using an enzymatic reaction. All study participants were asked to complete a short questionnaire regarding their GI symptoms.

Results showed the median levels of calprotectin found in the stools of patients with Parkinson’s disease were much higher compared to those found in the stools of healthy individuals (54.5 μg/g versus 9.7 μg/g), indicating the presence of bowel inflammation.

“Additionally, we evaluated the percentage of subjects with abnormal results considering the following age-dependent upper cut-off values of normal fecal calprotectin: 51 μg/g for subjects below 60 years of age, and 112 μg/g for subjects above 60 years. Abnormal fecal calprotectin level was found in 43% of all PD patients and in none of the control subjects,” the researchers stated.

Additionally, abnormal calprotectin levels were found more often among patients younger than 60 (50%) than among those who were older than 60 (39%).

No correlations were found between the levels of calprotectin found in the stool of patients and disease duration. Unlike calprotectin, no significant differences were found in the levels of zonulin between the two groups.

The most frequent GI symptoms patients reported in questionnaires included constipation (69%), feeling of incomplete evacuation (51%), bloating (51%), abdominal pain (20%), and changes in bowel movements (17%).

“The results of the present study confirm that [Parkinson’s disease] is characterized by the gut immune system activation,” the researchers said.

“The evaluation of fecal calprotectin level may be a useful tool to detect the signs of gut immune system activation present in a remarkable number of [Parkinson’s disease] patients, also in the early stage of the disease. Calprotectin may constitute a critical link between amyloid formation and neuroinflammatory cascades serving as a prospective diagnostic and therapeutic target,” they added.

The post Stool Calprotectin May Be Used as Marker of Bowel Inflammation in Parkinson’s Patients, Study Finds appeared first on Parkinson’s News Today.

People With Bipolar Disorder Face Higher Risk of Later Developing Parkinson’s, Study Finds

bipolar disorder

People with bipolar disorder have a significantly increased risk — more than three times that of the general population — of later developing Parkinson’s disease, a study has found.

Although use of medications for bipolar disorder could overestimate this risk, the researchers believe that a Parkinson’s diagnosis should be considered if patients with the mental health condition also show parkinsonian features.

The study, “Risk of Developing Parkinson Disease in Bipolar Disorder – A Systematic Review and Meta-analysis,” was published in JAMA Neurology.

Biopolar disorder is a mood disorder characterized by cyclic episodes of depression and mania. Although the mechanisms underlying bipolar disorder are still not completely understood, there is a possible role of the dopaminergic system — which is affected in Parkinson’s disease.

In fact, antipsychotic medications that block dopamine receptors can improve manic symptoms in these patients.

Certain medications used to treat bipolar disorder — such as lithium, antipsychotic medications, and antiepileptic medications — could be associated with drug-induced parkinsonism, which cannot be effectively distinguished from Parkinson’s disease in the clinic.

“Since drug-induced parkinsonism is more common among patients with [bipolar disorder], physicians may be more inclined to misdiagnose PD as drug-induced parkinsonism,” the researchers said.

Some studies also have shown that bipolar disorder is more common in people with Parkinson’s.

To understand the possible association of bipolar disorder with a later diagnosis of idiopathic Parkinson’s disease — meaning it’s due to an unknown cause — researchers from the University of Lisbon in Portugal performed an electronic literature search across four medicine-related databases.

Data from seven studies, involving 4, 374, 211 total participants, were used. The selected studies contained data on the likelihood of developing Parkinson’s disease in individuals with bipolar disorder versus those who did not have this condition.

The results showed that those with bipolar disorder were 3.4 times more likely to develop Parkinson’s disease later in life. Even when accounting for studies that had a high risk of bias, this likelihood was still maintained, albeit lower, at 3.21 times greater risk.

Researchers then performed a subgroup analysis in which they divided participants based on the duration of their follow-up. Specifically, they split patients into two groups: one including participants with more than nine years of follow-up versus those who were followed for less time.

Both groups had an increased risk of developing Parkinson’s, but the subgroup with the shorter follow-up was associated with a greater increase in the risk of a PD diagnosis.

However, this could be due to a higher rate of misinterpretation of drug-induced parkinsonism as Parkinson’s disease. “In fact, one study explicitly did not differentiate between the 2 conditions,” the researchers said.

“This review suggests that patients with [bipolar disorder] have a significantly increased risk of developing PD compared with the general population,” the researchers said.

They added that, if patients with bipolar disorder show parkinsonism features, a Parkinson’s diagnosis should be considered “independently of concomitant medication.”

The investigators said further testing could help to determine whether patients presented Parkinson’s versus drug-induced parkinsonism.

“To clinically distinguish parkinsonism from PD in clinical practice, the use of functional neuroimaging methods may be of particular interest,” they said.

“The main clinical implication of this review should be to underline that if patients with [bipolar disorder] present with parkinsonism features, this may not be drug induced and may recommend the investigation of PD,” the researchers concluded.

The post People With Bipolar Disorder Face Higher Risk of Later Developing Parkinson’s, Study Finds appeared first on Parkinson’s News Today.

Nourianz Now Available in US as Add-on to Carbidopa/Levodopa to Treat Parkinson’s Off Periods

Nourianz tablets

Kyowa Kirin’s Nourianz (istradefylline) tablets are now available in the United States as an add-on treatment for off periods in Parkinson’s disease patients on a carbidopa/levodopa regimen.

Off periods — when the effects of a medication wear off before a new dose can be taken — are characterized by the re-emergence of Parkinson’s motor symptoms and are typically more common as the disease progresses. Within five years of starting levodopa/carbidopa therapy, approximately 50% of patients may experience off periods.

“We are pleased to offer patients Nourianz, the first and only FDA-approved adenosine A2Areceptor antagonist treatment for ‘off’ time associated with [Parkinson’s],” Tom Stratford, president of Kyowa Kirin USA Holdings, said in a press release. “Nourianz administered with levodopa/carbidopa therapy can help reduce ‘off’ time and increase ‘on’ time without troublesome dyskinesia.”

Nourianz blocks a receptor, known as the adenosine A2A receptor, found at high levels in the basal ganglia, a region of the brain that controls movement. By blocking this receptor, Nourianz can alter the release of neurotransmitters — chemical substances produced in response to nerve signals that allow nerve cells to communicate — in the basal ganglia, regulating motor activity.

The U.S Food and Drug Administration (FDA) approved Nourianz in August based on the results of four randomized, placebo-controlled Phase 2 and 3 clinical trials (NCT00955526, NCT00455507, NCT01968031, and NCT00250393).

The trials assessed the safety and efficacy of two doses (20 mg and 40 mg) of Nourianz to reduce the mean total hours of awake time per day spent in the off state and also lessen motor symptoms.

A total of 1,143 Parkinson’s patients taking levodopa/carbidopa, levodopa/benserazide, or levodopa and any other dopa-decarboxylase inhibitor were recruited. Treatment with Nourianz significantly decreased daily off time, compared with patients on a placebo, and improved motor function.

The most common side effects of Nourianz included involuntary muscle movement (dyskinesia), dizziness, constipation, nausea, hallucinations, and insomnia.

“In my clinical practice, I see patients who experience the troublesome effects of Parkinson’s disease and ‘off’ episodes that interfere with activities of daily living,” said Peter A. LeWitt, MD, a professor of neurology at Wayne State University School of Medicine and director of the Parkinson’s Disease and Movement Disorders Program, Henry Ford Hospital.

“Nourianz represents an important milestone and provides U.S. patients and their caregivers with a nondopaminergic, once-a-day oral treatment option to significantly decrease the amount of ‘off’ time,” LeWitt added.

Nourianz has been marketed in Japan under the brand name Nouriast since May 2013.

The post Nourianz Now Available in US as Add-on to Carbidopa/Levodopa to Treat Parkinson’s Off Periods appeared first on Parkinson’s News Today.

Polypharmacy Linked to Cognitive Decline in Newly Diagnosed Parkinson’s Patients, Study Finds

Polypharmacy

Taking several different medications at the same time to treat concurrent health conditions — known as polypharmacy — may be associated with cognitive decline in people newly diagnosed with Parkinson’s disease, according to a recent study.

Reducing the number of medications prescribed would be one option to minimize the potentially harmful effects of polypharmacy on patients’ cognitive abilities, the researchers said.

The study, “Polypharmacy Associated with Cognitive Decline in Newly Diagnosed Parkinson’s Disease: A Cross-Sectional Study,” was published in the journal Dementia and Geriatric Cognitive Disorders.

Polypharmacy — most commonly defined as taking five or more medications concurrently for different conditions — is an emerging concern, particularly for the elderly. It has been associated with falls, adverse medication events, and hospitalization, researchers say.

A previous study found that polypharmacy also is associated with cognitive impairment in older adults who live independently.

However, its effects on the cognitive function of newly diagnosed patients with Parkinson’s disease — a neurodegenerative disorder associated with cognitive impairments and, at later stages, dementia — are still unclear.

In this study, investigators from the University of Miyazaki in Japan set out to explore the possible association between polypharmacy and cognitive decline in people who were recently diagnosed with Parkinson’s.

The cross-sectional study enrolled 131 patients who had been consecutively hospitalized at the University of Miyazaki Hospital and were newly diagnosed with Parkinson’s. Participants were divided into two groups, depending on whether they met the criteria for polypharmacy — which was defined for this study as taking six or more medications to treat different health conditions.

Cognitive function was assessed in all study participants using the Mini-Mental State Examination (MMSE) and compared between the two groups. All comparisons were normalized for potential confounders, including age, sex, education and medical history.

Among the 131 patients (mean age 69.8 years, 46.6% male) enrolled in the study, 43 (32.8%) met the criteria for polypharmacy.

After performing data adjustments for possible confounders, researchers found that the individuals who met the polypharmacy criteria had significantly lower MMSE scores compared with those who did not (26.2 versus 27.7). These results were indicative of cognitive decline.

“This is the first study to demonstrate an association between polypharmacy and cognitive decline in patients with newly diagnosed PD [Parkinson’s disease], as well as in community-dwelling older adults,” or people living independently, the researchers said.

“Medication reduction might be a promising intervention to prevent the development of dementia in patients with early PD,” the investigators said.

“Further prospective studies are needed to confirm whether medication reduction in patients with newly diagnosed PD can improve cognitive function and prevent the development of dementia,” they added.

The post Polypharmacy Linked to Cognitive Decline in Newly Diagnosed Parkinson’s Patients, Study Finds appeared first on Parkinson’s News Today.

‘Get It On Time’ Petition Seeks Better Access to Parkinson’s Meds in UK

petition

A healthcare petition called “Get It On Time” is circulating in the U.K. among people with Parkinson’s disease (PD). According to the petition, hospitalized PD patients are not getting the medications they need on time, if at all.

Over 700 patients in the U.K. were surveyed from May to July. Seventy-eight percent said their health suffered setbacks as a result of missed medications, including tremors, anxiety, decreased mobility, and communication issues. The Guardian health policy editor Denis Campbell noted that some Parkinson’s patients are unable to walk or talk because they don’t get their medications on time.

On Twitter, David Sangster, a Parkinson’s advocate in the U.K., described his hospital experience as a “caring environment, clean and professional. The visiting specialists nurses were … experts in every facet of PD, they were remarkable. … But #parkinsons was not understood on the ward and that’s wrong.”

Dawn Iola Chappell, another U.K. resident, responded to a tweet regarding the petition by saying, “[M]y Dad did not get his medication on time and it was the beginning of the end.”

It’s not just an issue in the UK

Before my deep brain stimulation surgery, my doctor told me to bring my medications to the hospital and administer them myself. The staff was unaware of the importance of distributing medications accurately or on time. Hospitals can be a frightening place, so it’s important that you take an active role in your healthcare, no matter how much you trust your medical team.

When medication schedules are not adhered to, a variety of problems can occur. The patient may begin to flail about. Tremors that were under control may worsen, or the patient may appear to be experiencing seizures. In response, hospital staff might treat the patient for seizures, resulting in dangerous and even fatal outcomes, which you can read about here.

What can you do now to prevent a mishap later? If possible, people with PD should have an advocate with them who knows the medication schedule and can help with administration should the need arise. One patient suggested the use of flashcards when a patient is coherent but unable to communicate verbally. For example, one of the flashcards could include: “Need PD meds now!”

If you’re a resident of the U.K., consider signing the petition. Every name helps!

***

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

The post ‘Get It On Time’ Petition Seeks Better Access to Parkinson’s Meds in UK appeared first on Parkinson’s News Today.

Veterans with PTSD or Brain Injury at Risk of Sleep Disorder That Might Signal Parkinson’s, Study Finds

sleep disorders and vets

Military veterans with post-traumatic stress disorder (PTSD) or who experienced a traumatic brain injury have more than double the risk of a rare sleep disorder — called rapid eye movement (REM) sleep behavior disorder — previously reported as a risk factor for Parkinson’s disease, a study finds.

Researchers at the VA Portland Health Care System and Oregon Health and Science University, who were responsible for this study, are now planning to explore this association and the incidence of Parkinson’s among veterans with REM sleep behavior disorder (or RBD).

“This is important because, in the general population, RBD has been linked to Parkinson’s disease, and RBD often precedes classic symptoms of Parkinson’s by years,” Miranda Lim, MD, PhD, a staff physician at the VA and the study’s senior author, said in a news release.

The study, “Post-traumatic stress disorder increases odds of REM sleep behavior disorder and other parasomnias in Veterans with and without comorbid traumatic brain injury” was published in the journal SLEEP.

RBD is characterized by uncontrolled and violent arm and leg movements, and acting out dreams during sleep. This sleep disorder has been specifically linked to the development of synuclein-related diseases. RBD of no known cause, called idiopathic RBD, occurs in approximately 1% of the general population.

Previous studies suggest that people with RBD are at a greater risk of neurodegenerative disorders — such as Parkinson’s and dementia — with 6.25% of them acquiring an overt neurodegenerative disease within a mean period of 4.6 years. The risk of developing such diseases was also found to progressively increase, from 10.6% after two years to 73.5% after 12 years.

Veterans are at a particularly high risk of traumatic brain injury (TBI) and PTSD, and as such represent a “population enriched for a history of trauma.” Concussions and other mild brain injuries, which many experience during their military service, are also linked to an increased Parkinson’s risk. One study reported that veterans with any kind of traumatic brain injury had a 71% higher likelihood of Parkinson’s than other vets.

Researchers now evaluated veterans’ sleeping patterns according to their pre-existing history of brain injury or other neuropsychiatric trauma, investigating the prevalence of RBD in 394 veterans —mainly male (94%) and middle-aged (54.4 years) — and its association with TBI and PTSD.

Analysis of veterans’ sleep patterns, based on the electrical activity in muscles, found that 9% of them experienced RBD, 7% had higher muscle tone during REM or deep sleep — a condition known as REM sleep without atonia — and 31% had other sleeping problems (parasomnias). This suggested that RBD is considerably more common in veterans than the general population.

They found that veterans with a brain injury or PTSD had a higher incidence of parasomnias. In particular, among those with PTSD or PTSD plus brain injury only 32% and 20% had normal sleeping behaviors, while 56% of these people experienced REM sleep behavior disorder.

Overall, veterans with PTSD had 2.81 and 3.13 times higher odds of RBD and other parasomnias, while those with PTSD plus TBI had 3.43 and 3.22 times higher odds of RBD or other parasomnias.

Given the strong association between RBD and progressive neurodegenerative disorders, it remains to be determined whether RBD and neuropsychiatric symptoms “increases the risk of similar long-term neurologic sequelae [consequences],” the researchers wrote.

“We don’t know whether veterans who have PTSD and higher rates of RBD will go on to develop Parkinson’s, but it is an important question we need to answer,” Lim said. “If you could intervene when people first start to show RBD, maybe you could prevent later symptoms of Parkinson’s.”

The post Veterans with PTSD or Brain Injury at Risk of Sleep Disorder That Might Signal Parkinson’s, Study Finds appeared first on Parkinson’s News Today.

Safety and Efficacy of Oral Cannabidiol in Treating Parkinson’s Psychosis Focus of Phase 2 Study in UK

cannabidiol

A planned Phase 2 clinical trial will assess the safety and effectiveness of pharmaceutical-grade cannabidiol (CBD) in treating Parkinson’s-related psychosis.

The trial was announced by Parkinson’s UK, which is investing £1.2 million (roughly $1.5 million) to support the study, due to begin enrolling patients in 2020.

Psychosis is estimated to affect more than half of people with Parkinson’s disease. It is characterized by hallucinations (seeing, hearing, or feeling things that are not really there) and delusions (fixed beliefs that are demonstrably untrue).

These symptoms are typically managed by reducing or stopping the use of medications used to treat Parkinson’s, but such choices have the obvious drawback of arresting any benefits those treatments provide. Antipsychotics are sometimes also used, but they can carry side effects or worsen motor symptoms.

Nuplazid (pimavanserin, by Acadia Pharmaceuticals) is the only medicine currently approved to treat Parkinson’s-related psychosis in the United States; no approved therapies for this condition are available in the United Kingdom.

“Current treatments prescribed by clinicians for psychosis typically work by blocking dopamine receptors, which can increase the problems people with Parkinson’s experience with movement and other symptoms of the condition,” Sagnik Bhattacharya, a professor at King’s College London who will help lead the trial, said in the press release.

This trial will “will determine, for the first time, whether CBD can correct the abnormal functioning of the brain that is causing symptoms such as hallucinations and delusions,” Bhattacharya added.

Cannabidiol is a non-psychoactive component of the cannabis plant, meaning it is found in cannabis, but unlike tetrahydrocannabinol or THC does not induce a feeling of being “high.” CBD is currently undergoing a renaissance of interest for its potential medical uses.

“We know from a recent survey we carried out, that people with Parkinson’s would continue to use, or start using, cannabis-derived products if robust evidence became available that they are safe and effective in treating Parkinson’s symptoms,” said Arthur Roach, PhD, the director of research at Parkinson’s UK. “One of the key questions this clinical trial will address is if CBD is safe to use for Parkinson’s-related psychosis, which has never been done before.”

The two-part study will begin with a six-week pilot phase to evaluate the safety, tolerability and effectiveness of CBD in people with Parkinson’s-related psychosis. Participants will be given daily oral CBD capsules at doses up to 1 gram per day to find the optimum dose. Then, 120 patients will be randomized to treatment with either CBD or a placebo for 12 weeks.

In addition to safety, trial goals (endpoints) will include a detailed assessment of psychotic, motor and non-motor symptoms, as well as brain imaging.

“We will be assessing how safe CBD is for people with Parkinson’s, what the correct dosage is and how it is tolerated alongside the different medications someone with the condition may already be on,” Bhattacharya said. “The study will also look at the effect of CBD on other symptoms which will pave the way for scientists to investigate the potential of the compound in treating these in future studies.

“We hope that this will progress to large-scale clinical trials — the final step towards becoming a new treatment that will improve the lives of people with Parkinson’s,” Bhattacharya added.

If successful, this study “could result in a regulated cannabinoid-based medicine being prescribed and used in the clinic, as opposed to self-administration of expensive supplements that have not been monitored for their composition or effects,” Roach said.

The post Safety and Efficacy of Oral Cannabidiol in Treating Parkinson’s Psychosis Focus of Phase 2 Study in UK appeared first on Parkinson’s News Today.

Mutations in Alpha-Synuclein Speed Protein Clumping in Familial Parkinson’s and Affect Severity, Study Finds

alpha-synuclein and A53T

A detailed analysis of alpha-synuclein — a key protein involved in Parkinson’s — revealed how variants of this protein change over time, allowing researchers to identify the initial stages of protein aggregation involved in early onset disease.

These findings provide new insights into how genetic mutations — especially the point mutation A53T — can contribute to familial Parkinson’s, and into understanding why this disease form manifests earlier and is often more severe than sporadic (of unknown cause) Parkinson’s.

The study, “Alpha-synuclein stepwise aggregation reveals features of an early onset mutation in Parkinson’s disease,” was published in the journal Communications Biology.

Parkinson’s is largely a sporadic disease, with 15% to 25% of all cases linked to inherited genetic mutations. One of the first genes identified as directly associated with Parkinson’s, leading to early onset disease, was the alpha-synuclein coding gene SNCA.

It is widely accepted that alpha-synuclein is an important element that drives nerve cell death across several human neurodegenerative disorders, including Parkinson’s and dementia with Lewy bodies. Its toxic effect is, at least in part, tied to the formation of abnormal protein aggregates or clumps.

Despite available knowledge of the damaging impact alpha-synuclein clumps have on nerve cells, the process by which alpha-synuclein changes from a single protein structure into an aggregate form remains poorly understood.

Researchers at the Federal University of Rio de Janeiro (UFRJ) in Brazil conducted a series of biochemical, kinetic, and structural studies to address this gap.

They evaluated in detail the behavior of alpha-synuclein — both its normal form as well as mutated versions found in people with familial Parkinson’s — and its ability to form toxic clumps.

“The conversion from one protein stage to the other takes place slowly. The intermediate structures and the amyloid aggregates accumulate over time in the brain. So far, we don’t know which species cause the symptoms and toxicity to cells,” Guilherme A. P. de Oliveira, a professor at UFRJ and the study’s lead author, said in a press release.

“If we understand the protein species forming during the early stages of disease conversion, we can propose new therapies for disease detection before the symptoms appear.”

Results showed that the versions of alpha-synuclein carrying A53T, A30P, or E46K point mutations were able to from small aggregates (known as oligomers) at a much faster rate than a normal version of the protein.

Of note, point mutations are genetic alterations where a single nucleotide — the building blocks of DNA — is changed, inserted, or deleted from a sequence of DNA. If you think of DNA as a Lego train, a point mutation would be the same as changing, adding, or taking out a single piece. 

Next, the researchers used cutting-edge imaging techniques to visualize for the first time, in detail and over time, all the elements involved in the expansion of alpha-synuclein aggregates — their transition from early oligomers to intermediate fibrils to late filaments.

“By (…) acquiring advanced electron microscope images, we are able to better understand these wrong protein associations in their native environment and [potentially find] ways to avoid their formation,” Oliveira said.

This approach showed that the different protein versions give rise to structurally different fibrils.

The expansion of fibrils into long filaments was found to be dependent on the ability of alpha-synuclein to continue to recruit available oligomers.

Interestingly, the A53T point mutated version was able to overcome some of the limits on protein clumping imposed by the surrounding environment, and for which normal alpha-synuclein showed a sensitivity. This suggests that A53T mutations give alpha-synuclein a greater potential to promote aggregation and induce faster spreading of its toxic clumps.

“Our findings place A53T with features that may explain the early onset of familial Parkinson’s disease cases bearing this mutation,” the researchers concluded.

The post Mutations in Alpha-Synuclein Speed Protein Clumping in Familial Parkinson’s and Affect Severity, Study Finds appeared first on Parkinson’s News Today.