Embracing the Beauty and Serenity of My Sanctuary

sanctuary

Sunlight bounces its way through the swaying birches, projecting a shadow picture show on the lawn and garden shed. A light wind causes the fluttering leaves to sing in unison like waves on the shore. A family of hummingbirds — we have given all of them names now — take turns to show off their aerial ballet at the feeder, a few feet from my rocking chair. The gardens are still blooming with cranberry-red coneflowers nestled between large-cupped orange and yellow day lilies. In the distance, I hear the sweet, calming vibrato of our brook. It beckons me to embrace the support revealed within my sanctuary.

Sanctuary can be found and created anywhere. It doesn’t have to be Walden Pond or resemble my description. What is important is the frame of mind used when accessing sanctuary. Sanctuary is that place where the saying, “You get back out what you put in,” truly applies. If I can embrace the awe and beauty of my sanctuary while also experiencing its solitude, safety, serenity, and sacredness, then I know that I am in the right frame of mind.

Sanctuary is more than a sacred physical place. The physical merely signals the senses to be ready for the well-being phenomena. The physical sanctuary supports the emotional and spiritual sanctuary. It is from this inner stance that I seek calm and a trusting openness, and prepare to experience the journey. I have a relationship with my sanctuary, and this “agreement” is the first step to incorporating sanctuary into a wellness plan.

Architects realize the importance of creating healthy living and work environments. Designs for buildings and the areas they occupy, whether in a rural or urban setting, are incorporating a sense of sanctuary for well-being. Providing for “green space,” buffers, and integration with the natural environment are key concepts for architects. “Architecture helps shape the quality of our environments and can contribute to health and happiness,” writes Karl Johnson in the Guardian. Sanctuary is rooted in the beauty of nature. The “N” in the CHRONDI Creed, stands for “nature” and its health benefits.

Let me share my story of sanctuary. The week had been hectic, even busier than usual. It started with a trip to my general medical provider’s office for fasting lab work. It’s almost a two-hour drive on an empty stomach until after the labs are drawn, which throws off my Parkinson’s medications. The next day, we took a trip to Boston for my appointment at a Veterans Affairs healthcare facility. That trip takes two days, so we usually drive down the day before the appointment to break up the journey. We stay at a hotel, then arise the next morning to complete the four-hour drive to the clinic.

The appointments are never fun. At least this one didn’t require the providers to poke, prod, or inject. Well, maybe some poking, but no injections. Then we drove home, another four hours on the road. With my rigid Parkinson’s, every minute of travel increases my discomfort. No time to rest because I’m back at the doctor’s office a day later for the lab results.

The day after the doctor’s appointment, we run errands, and my partner hand-delivers her application to the state offices for “designated caregiver” status. We didn’t have the energy to attend a live theater presentation on Galileo or the monthly get-together for the New England Santa Society. Or celebrate our anniversary. We make decisions every week about where to spend our free time; this includes letting go of some plans in favor of time spent with sanctuary.

Weeks like the one that I describe are more difficult for me. I require several days to recuperate and recover. The fatigue is almost overwhelming, preventing me from returning to my projects as much as I would like. My mind is tired, my body drained, and my soul seeks out my sanctuary. I don’t need to have faith that sanctuary will help; I know from personal experience that it will.

You can create a sanctuary in your home, in a favorite room or comfortable chair. You can build a garden along a walkway. Perhaps you will find, as I do, that I can create several different areas, each unique to the landscape, plants, and season. I enjoy the beauty of each special place within my quiet sanctuary. What is important is your ability to embrace that special sacred physical place, the sanctuary that offers you the greatest support for well-being.

***

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

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$2.8M NIH Grant Targets Proteins Involved in Brain Disorders

NIH grant

The National Institute of Neurological Disorders and Stroke, of the National Institute of Health (NIH), has awarded a large grant to researchers who are seeking to understand the molecular structure of toxic proteins that drive brain disorders.

Irregular clumps of certain proteins are thought to be the root cause of several neurological disorders: alpha-synuclein and amyloid-beta proteins are linked with Parkinson’s disease and Lewy body dementia (which often occur simultaneously), and amyloid-beta and tao are involved in Alzheimer’s disease.

The new grant awards $2.8 million over five years to study the structure of these proteins. The project is being led by researchers at Mayo Clinic’s Florida Campus and at Columbia University in New York.

The researchers plan to use new imaging technologies, namely single-particle cryo-electron microscopy (cryo-EM) and cryo-electron tomography (cryo-ET), to investigate these proteins in more detail than ever before.

Cryo-EM — a technology that shared the 2017 Nobel Prize in Chemistry — uses beams of electrons to investigate the structure of proteins with atomic-level resolution. Researchers plan to use it to view proteins in samples of brain tissue from people with neurological disorders like Parkinson’s.

Cryo-ET allows for the visualization of proteins within living neurons, which  researchers hope will provide important information about how these protein clumps end up killing brain cells.

“To truly understand the link between proteins and disease, we must discover how they interact with each other and with the surrounding brain tissue,” one of the researchers who will lead the project, Anthony Fitzpatrick, PhD, a professor at Columbia, said in a press release. “Cryo-EM’s power lies in its ability to reconstruct any protein at the level of individual atoms. This, combined with cryo-ET, which helps us understand how each protein behaves inside individual brain cells will, ultimately, enable us to learn how this behavior causes cells to die,” he said.

“[W]e hope to discover whether different proteins work in concert to spur disease progression,” Fitzpatrick added. “The combined use of cryo-EM and cryo-ET marks a tremendous leap forward from traditional, in vitro methods, which study the proteins’ behavior in a petri dish and thus do not replicate their natural environment.”

“One of the most imperative quests of our time is the understanding of brain function and the mechanisms of neurodegeneration,” said Rui Costa, DVM, PhD, the director of Columbia’s Zuckerman Institute. “This endeavor will allow us to have unprecedented insight into the 3D molecular structure of the aggregates that form in many neurodegenerative disorders, which ultimately can be critical for early diagnosis, prevention and treatment of these disorders.”

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Rhode Island Professor Receives More Funding for ‘Smart Glove’ for Parkinson’s Patients

smart glove grant

The National Science Foundation (NSF) has awarded a University of Rhode Island (URI) professor nearly $250,000 to help commercialize a “smart glove” for Parkinson’s disease patients.

Kunal Mankodiya, PhD, an associate professor of engineering, is developing the glove that can capture wearers’ movement data. Designed for those with PD or other movement disorders, the technology can help physicians customize patients’ exercise and treatment regimens.

The two-year project grant is through the NSF’s Partnerships for Innovation program, which helps researchers accelerate innovations that address significant societal needs. The project received NSF funding earlier.

“This funding will enable us to take a deep dive into the world of fusing different domains, including conductive fabrics, wearable electronics, human-factors design and smart textile manufacturing,” Mankodiya said in a press release. “I’m glad that the NSF created such grant programs where innovative technologies could find their way to the marketplace over the years.”

It’s been three years since Mankodiya, with the help of students in his Wearable Biosensing Lab, designed the first prototype of the glove. “We’ve performed significant research on the smart gloves over the years. We decided that it’s time to transition this technology from research to market. However, the transition is not straightforward. It will require very focused, narrow research to finalize the physical, digital and analytical components of the smart gloves,” he said.

Nick Constant has been there since the start. The URI electrical engineering doctoral student designed the proof-of-concept glove that earned the original NSF grant. Along with Mankodiya, he also wrote the new grant proposal. “Its ultimate outcome seemed clear from the beginning, but building a new technology takes time and testing,” he said. “We have seen this glove go from a hopeful idea to gaining traction in reality through different design iterations and consultations with stakeholders.”

Constant’s charge these days is to find project collaborators knowledgeable about areas such as manufacturing, supply chains and medical device regulations. Ultimately, the team wants an affordable glove that’s relatively easy to manufacture.

Neurologist Umer Akbar, MD, project collaborator and co-director of Rhode Island Hospital’s Movement Disorders Program, specializes in those living with Parkinson’s, and sees a definite need for the wearable device. “The challenge with studying the many symptoms of the disease is that they fluctuate throughout the day,” he said. “The short window physicians have into their patients’ lives is often inadequate to verify the symptoms, so we sought to develop wearable technology that can remotely and objectively provide clinical data which can help us better treat our patients.”

In a pilot study to take place in Mankodiya’s lab, at Rhode Island Hospital, and in patients’ homes, up to 30 Parkinson’s patients will try the glove.

Andrea Hopkins has worn the glove a few times since its development. Diagnosed with Parkinson’s in 2002, the former URI assistant vice president of public affairs eagerly awaits the finished version.

“There is no cure for Parkinson’s disease, but if doctors can monitor their patients remotely using the smart glove, it would enable them to assess how the medications are working,” she said.

Many stand to benefit from the glove’s successful development. The neurodegenerative disorder affects roughly 1 million U.S. residents, and more than 10 million individuals globally.

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Two Parkinson’s Organizations Issue a Total of $5.9M in Research Grants

research grants

The Parkinson’s Foundation and the American Parkinson Disease Association (APDA) have announced a combined $5.9 million in research grants.

For its part, the Foundation is investing $4.2 million in 46 grants to advance promising Parkinson’s disease investigations into new therapies and how the disease works. It also is awarding $8 million to four newly designated Parkinson’s Foundation Research Centers to design and launch studies over the next four years.

“The Parkinson’s Foundation is committed to moving the needle forward in new treatments, medications and better understanding symptoms and disease progression,” John Lehr, the Foundation’s president and CEO, said in a press release. “These research grants are a critical component in our mission to make life better for people with Parkinson’s by improving care and advancing research towards a cure,” he said.

Ranging in length from several months to three years, the awards will go to clinicians and postdoctoral researchers, as well as established scientists. In addition, this grant cycle adds the Melvin Yahr Early Career Award in Movement Disorders Research, created to support post-residency neurologists. The two-year $50,000 grant will support study into brain inflammation in Parkinson’s patients.

“This award is critical for my early independent career development and will help me establish a research program of my own,” said Yulan Xiong, assistant professor at Kansas State University and Stanley Fahn Junior Faculty Award recipient. “The support from the Parkinson’s Foundation will help us better understand a critical PD-related gene. We expect this study will lead to new discoveries in Parkinson’s disease.”

The $8 million in institutional grants — $2 million for each center — will go to Columbia University Irving Medical Center, the University of Florida in collaboration with Emory University, the University of Michigan in collaboration with the University of Texas Southwestern Medical Center, and Yale School of Medicine. These recipients were chosen based on criteria such as research novelty and the ability to address unmet needs in Parkinson’s research.

More information about Parkinson’s Foundation research grants is available here.

At the American Parkinson Disease Association, researchers have been granted $1.7 million for study programs including T-cells and their disease role, genetic factors among Hispanic populations, and the prospects of telehealth psychotherapy in relieving depression.

Awardee highlights include Vikram Khurana, MD, PhD, Brigham and Women’s Hospital in Boston, Massachusetts, winner of the three-year George C. Cotzias Fellowship, the APDA’s most prestigious grant.  He will seek to learn how alpha-synuclein mutation or over-expression affects mRNA regulation in Parkinson’s, which could helpscientists to identify new therapeutic targets and potential gene therapies.

Livia Hecke Morais, PhD, California Institute of Technology, is a post-doctoral fellow who will study microbial brain interaction in Parkinson’s neurodegeneration to understand the relationship between gut bacteria and the disease. This ultimately may lead to the design of new therapies that target gut bacteria for treating Parkinson’s disease.

Research fellow Brian Daniels, PhD, Rutgers University in New Jersey, will investigate RIPK3, a protein associated with Alzheimer’s and amyotrophic lateral sclerosis, as a driver of  inflammation in Parkinson’s disease.

Research fellow Xianjun Dong, PhD, Harvard Medical School in Boston, will explore the possibility of a novel link between genetic susceptibility and Parkinson’s disease.

“We are excited for these researchers to dig deep into their work, and have hope for meaningful outcomes that can make a difference for people living with PD,” the APDA announcement stated.

A list of awardees and descriptions of research projects is available here.

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‘Exergaming’ on Stationary Bicycle Eased Parkinson’s Motor Problems

exergaming

Exercising at home with a stationary bicycle — using a motivational app and remote supervision to increase compliance — eases motor complications in patients with mild Parkinson’s disease and improves their cardiovascular health, according to results from a clinical trial.

Findings from the study, “Effectiveness of home-based and remotely supervised aerobic exercise in Parkinson’s disease: a double-blind, randomised controlled trial,” were published in the journal The Lancet Neurology.

Though high-intensity aerobic exercise has shown motor benefits in people with Parkinson’s, the effectiveness of home-based programs in a broader patient population has not been determined.

A team from Radboud University Medical Center, The Netherlands, designed the “Park-in-Shape” intervention that incorporates virtual reality software and real-life videos — a so-called “exergaming” approach — to make exercising on a stationary bicycle at home more engaging.

Overall, the single-center, randomized trial (NTR4743) tested whether this type of aerobic exercise would improve motor function in patients with mild disease severity (a Hoehn and Yahr stage 2 or less) who were on stable dopaminergic treatment or not yet started on such therapies.

To be included, the patients (ages 30–75) had to exercise less than is recommended for older adults, meaning vigorous exercise over 20 minutes up to two times per week, or moderate exercise over 30 minutes up to four weekly sessions.

The study compared two groups, in which all 130 patients exercised three times per week over six months and were on stable dopaminergic medication (stable dose for at least one month), or were still without treatment and expected not to start treatment within the next month.

But while 65 patients performed stretching, flexibility and relaxation exercises in 30-minute sessions (control group), the other 65 patients exercised for 30 to 45 minutes on the stationary bicycle at home (intervention group). The patients were instructed to cycle at a target heart rate zone, which was gradually increased as the participants became fitter.

All participants had a motivational app with tips for optimal training, support from loved ones, and information to track progress. All were supervised once at home and also remotely every two weeks.

Patients were evaluated during their “on” and “off” states — when dopaminergic medication is still effective, or when it wears off.

Results showed that the patients exercising on the stationary bicycle had  significantly better motor function after six months. Specifically, in their “off” state, the increase in their Movement Disorders Society—Unified Parkinson’s Disease Rating Scale score was 4.2 points lower than that of the controls. Also, unlike the controls, patients on aerobic exercise experienced improvements in cardiovascular fitness by the end of the study.

“Aerobic exercise can be done at home by patients with Parkinson’s disease with mild disease severity and it attenuates [lessens] off-state motor signs,” the scientists wrote.

In contrast, no benefits were seen in non-motor complications such as fatigue, anxiety, depression, or cognitive function, which the researchers attribute to the short duration of the intervention.

Over the span of the study, the mean number of aerobic exercise sessions was 54, while that of the control sessions was 60. This corresponds to 75% and 83% of the expected 72 sessions for each group, respectively.

“We were pleasantly surprised that people with Parkinson’s disease were able to adhere to their exercise regimes so well,” Nicolien van der Kolk, the study’s lead author, said in a press release. “The beneficial effect on their motor disability was also large enough to be clinically relevant. As such, exercise is a very useful addition to the medication.”

Five patients were lost to follow-up, four of whom were in the cycling group. Ten patients in each group did not complete their assigned intervention, with technical issues being the main reason for discontinuation in the cycling group. However, as they attended the follow-up visit, these patients were included in the analysis.

Eleven patients experienced adverse events (AEs, or side effects) potentially related to the intervention, seven of whom were in the cycling group. These included back or joint pain and palpitations. Three patients discontinued exercise due to AEs.

In turn, the seven serious AEs observed (three in the cycling group) were all unrelated to the program. They included knee and fall-related injuries, hip fracture, and severe dyskinesias, which refer to involuntary, jerky movements.

“This study is very important,” said Bas Bloem, MD, PhD, the study’s principal investigator. “We can now start researching whether much more long-term cycling can also slow the disease progression.”

“Also, this new ‘exergaming’ approach that we have developed is very suitable to achieve long-term improvements in exercise behavior for patients with a range of other disorders that could also benefit from regular exercise,” Bloem said.

“Future studies should establish long-term effectiveness and possible disease-modifying effects,” the researchers concluded.

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Hope Is Good Medicine When Fighting Parkinson’s Disease

hope

I thought I knew what to expect. But I was hoping that the first opinion was incorrect — that they had missed something or seen something that wasn’t there.

I drove on, the second opinion soon to come.

Entering through the sliding glass doors, I made a right turn and pushed the elevator button. I ascended two floors, stepped out, made a left to the neurology department, and checked in. New patient paperwork filled out, I took a seat among others who sat waiting.

The wait was unusually short. When my name was called, I stood and followed the nurse back to the room that I would occupy for the next two hours.

White. All white.

The walls, the trash cans, the sheet of paper that covered the exam tables — everything was sterile white. Cold and uninviting. But then what is “friendly” about a doctor’s office? I would soon find out.

The nurse ran through the paperwork and repeated the questions that I had already answered with a pen. After taking my vitals, she stood, and as she turned to leave the room, she said, “The doctor will be right with you.”

“Yeah,” I thought. “Right with me.” At least I didn’t have to wait in the lobby. But before my thoughts had time to flourish, the door opened.

The doctor’s smile was wide as he stretched out his hand. He was dressed in slacks and sweater, his dark, curly hair pulled back into a neat ponytail and topped with a knit beret. After the introductions, he began “testing.”

Testing for Parkinson’s disease is different than for most other conditions. There are no blood or urine tests, or scans — at least, there weren’t then, nearly 20 years ago. These “tests” began with the following:

  •  Close your eyes.
  •  Start at 60 and count backward with your eyes closed.
  •  Arms out in front, palms up, palms down, tap thumbs and second fingers together, etc., etc.

He made notes for the next 20 minutes. Then he put his pen down, sat up straight, and with both feet on the floor, rolled his chair closer to me. Looking right at me, he put his hand on my knee. “I have to agree with Dr. So-and-So’s diagnosis. You have Parkinson’s disease. In fact, I think after reading through your records that they misdiagnosed you 12 years ago.”

That diagnosis, 12 years earlier, was lupus. I could have flushed all that Plaquenil (hydroxychloroquine) down the sink instead of swallowing it. But, Parkinson’s disease? I was only 43 — isn’t it an older person’s disease?

I have since learned that Parkinson’s disease doesn’t discriminate. It doesn’t matter what age, nationality, or gender you are. I thought that I knew what to expect when I drove 30 miles for that second opinion, but looking back, I know that I wanted to hear something else, such as, “Well, I’m not sure what Dr. So-and-So was thinking, but you’re the healthiest person I’ve ever met.”

Hope springs eternal.

Ah, hope

At a conference I attended on Parkinson’s disease, one of the speakers stated that the best medicine that we have when fighting any disease is hope. Hope for a better day, a breakthrough in research, a cure.

It’s easy to feel like giving in or giving up when you’re confronted with a challenge over which you seem to have no control — except your response to it.

After the appointment, I went outside into the rainy afternoon. I walked across the wet pavement, unsuccessfully sidestepped the puddles, got into my car, and closed the door. I shivered, and then cried.

My doctor didn’t tell me that I was the healthiest person he had ever met in all his years in medicine. He didn’t tell me that Dr. So-and-So was wrong or that I would get better. But he said that he’d be there with me to the end.

Hope is good medicine

Now, I know that you can’t hold a doctor to a promise like that, but the feeling that he cared gave me hope. The knowledge that I had someone who understood what I was going through, who would be on my side through my journey made me feel less alone.

Hope brings purpose back into view. It shuts out the “what-ifs” and turns down the dial of doubt. It disables the feelings of despair, enables you to have a confident expectation of a cure, finds the blessings in the curse, and faith for a brighter future.

I started the car, and as snow began to fall, a sense of peace came over me. All was well. I felt reassured that though I couldn’t choose to give back this disease, I could decide how I would face this challenge.

I chose hope.

***

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

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Antiparkinsonian Medication Improves Learned Movement Production by Boosting Neuronal Connectivity, Study Finds

Antiparkinsonian Medication

Dopaminergic therapy may ease difficulties with gesturing and using tools in people with Parkinson’s disease by improving brain connectivity between the cognitive and motor regions, a study has found.

The study results, “Dopaminergic modulation of the praxis network in Parkinson’s disease,” were published in NeuroImage: Clinical.

Parkinson’s patients often have trouble performing skilled or learned movements that are crucial for daily living. Praxis is what scientists call this kind of cognitively directed motor action, while apraxia, generally speaking, refers to the difficulty itself, i.e., any disorder of learned movement.

“Although the neuronal basis of praxis functions has been comprehensively investigated in healthy individuals, functional imaging studies targeting these abilities including their impairments in clinical samples are still rare,” the researchers wrote.

Medical University of Vienna researchers studied the functional connectivity of the praxis network in individuals with mild-to-moderate Parkinson’s and at an increased risk for apraxia. They also investigated the influence of dopaminergic therapy on praxis function-related brain network.

For this purpose, a total of 13 Parkinson’s patients (seven men and six women, mean age of 60.23 years) and 13 healthy controls (seven men and 6 women; mean age of 56.77 years) underwent functional magnetic resonance imaging (MRI) and apraxia assessments.

Functional MRI measures the small changes in blood flow that occur with brain activity in response to stimuli or actions.

In the Parkinson’s group, all tests were performed twice: once with individually optimized dopaminergic medication (“on” state) and once without (“off” state).

None of the participants had trouble imitating gestures upon demonstration of object use, and none of the Parkinson’s patients showed apraxia-like symptoms. However, patients in the off period (without optimized symptom control by medication) performed significantly poorer in praxis assessments than controls.

Regarding functioning of the praxis-related brain network, patients in both states (on and off) displayed higher global efficiency than healthy individuals. Further analysis revealed that most of the communication within the network relayed to the bilateral supramarginal gyri, a portion of the brain that is thought to be involved in language perception and processing.

In addition, patients with optimized dopaminergic medication showed higher connectivity between praxis and motor areas, particularly between the supramarginal gyrus and the primary motor cortex, basal ganglia, and frontal areas, in comparison to subjects in the “off” state.

This improved communication “might facilitate the propagation of long-term representations of object-related actions to motor execution areas,” thus enabling the correct execution of the wanted movement.

The praxis network was confined to the left-brain hemisphere in the control sample, while in patients “off” therapy, but not in “on” individuals, the  network expanded to the right hemisphere.

Importantly, antiparkinsonian treatment seemed to normalize patients’ learned movement skills and related network connectivity, suggesting such therapy may support higher-order cognitive motor functions, at least in early stages of this neurodegenerative disorder.

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CRISPR/Cas9’s Potential in Better Understanding and Treating Parkinson’s Focus of Review Study

gene editing and disease

In a recent review, scientists highlight the potential of gene editing technologies like CRISPR/Cas9 to not only understand the molecular mechanisms behind Parkinson’s disease, but also identify new targets for treatment.

The review study, “Interrogating Parkinson’s disease associated redox targets: Potential application of CRISPR editing,” was published in the journal Free Radical Biology and Medicine.

One of the hallmarks of PD is the loss of dopamine-producing neurons in the substantia nigra — a brain region involved in the control of voluntary movements, and one of the most affected in PD. This occurs due to the clustering of a protein called alpha-synuclein in structures commonly known as Lewy bodies inside neurons.

Parkinson’s is complex and multifactorial disease, with both genetic and environmental factors playing a role in either triggering or exacerbating the disease.

Genetic causes can explain 10% of all cases of PD —  called familial PD –, meaning that in the majority of the cases (sporadic PD) there is an interplay between genetics and environmental risk factors.

Researchers at Sechenov University in Russia and the University of Pittsburgh reviewed the role of metabolic pathways, especially problems with mitochondria — cells’ powerhouses — and iron accumulation, as well as mechanisms in cell death (called apoptosis and ferroptosis) in the development and progression of Parkinson’s disease.

These processes were discussed in the context of genome editing technologies, namely CRISPR/Cas9 — a technique that allows scientists to edit genomes, inserting or deleting DNA sequences, with precision, efficiency and flexibility.

“Empirical research has established many potential metabolic abnormalities that may represent the specific key mechanisms of PD pathogenesis. However, the diversity of these findings and the lack in understanding the connections between them slow down the progress in the development of specific treatments,” the researchers wrote. These abnormalities may be “[a]mong [the] many potentially important targets for CRISPR/Cas9 based research.”

“CRISPR is a promising technology, a strategy to find new effective treatments to neurodegenerative diseases,” Margarita Artyukhova, a student at the Institute for Regenerative Medicine at Sechenov and the study first author, said in a press release.

Mitochondria don’t work as they should in people with PD, resulting in shortages of cellular energy that cause neurons to fail and ultimately die, particularly dopamine-producing neurons. Faulty mitochondria are also linked to the abnormal production of reactive oxygen species, leading to oxidative stress — an imbalance between the production of free radicals and the ability of cells to detoxify them— that also damages cells over time.  

Because mitochondrial dysfunction is harmful, damaged mitochondria are usually eliminated (literally, consumed and expelled) in a process called mitophagy — an important cleansing process in which two genes, called PINK1 and PRKN, play crucial roles. Harmful changes in mitophagy regulation is linked with neurodegeneration in Parkinson’s.

Previous studies with animal models carrying mutations in the PINK1 and PRKN genes showed that these animals developed typical features of PD – mitochondrial dysfunction, muscle degeneration, and a marked loss of dopamine-producing neurons.

PINK1 codes for an enzyme that protects brain cells against oxidative stress, while PRKN codes for a protein called parkin. Both are essential for proper mitochondrial function and recycling by mitophagy. Mutations in both the PINK1 and PRKN gene have been linked with early-onset PD.

However, new research suggests that the role of PINK1 and PRKN in Parkinson’s could be more complex and involve other genes — like PARK7  (DJ-1), SNCA (alpha-synuclein) and FBXO7  — as well as a fat molecule called cardiolipin.

CRISPR/Cas9 genome editing technology may be used to help assess the role of different genetic players in Parkinson’s disease, and to look for unknown genes associated with disease progression and development. Moreover, this technology can help generate animal and cellular models that might help scientists decipher the role of certain proteins in Parkinson’s and discover potential new treatment targets.

Iron is another important metabolic cue in Parkinson’s. While it’s essential for normal physiological functions, excessive levels of iron can be toxic and lead to the death of dopamine-producing neurons in the substantia nigra.

Iron may also interact with dopamine, promoting the production of toxic molecules that damage mitochondria and cause alpha-synuclein buildup within neurons.

CRISPR/Cas9 technology can be used to help dissect the role of proteins involved in iron transport inside neurons, which in turn may aid in designing therapies to restore iron levels to normal in the context of Parkinson’s disease.

Finally, researchers summarized evidence related to the role of two cell death pathways — ferroptosis and apoptosis — in PD. Ferroptosis is an iron-dependent cell death mechanism by which iron changes fat (lipid) molecules, turning them toxic to neurons. This process has been implicated in cell death associated with degenerative diseases like Parkinson’s, and drugs that work to inhibit ferroptosis have shown an ability to halt neurodegeneration in animal models of the disease.

Apoptosis refers to a “programmed” cell death mechanism, as opposed to cell death caused by injury. Both apoptosis and ferroptosis speed the death of dopaminergic neurons.

CRISPR/Cas9 may help to pinpoint the key players in cell death that promote the loss of  dopaminergic neurons in Parkinson’s disease, while understanding the array of proteins that are involved in these processes.

“These insights into the mechanisms of PD pathology [disease mechanisms] may be used for the identification of new targets for therapeutic interventions and innovative approaches to genome editing, including CRISPR/Cas9,” the researchers wrote.

Genome editing technology is currently being used in clinical trials to treat patients with late-stage cancers and inherited blood disorders, Artyukhova notes in the release.

These “studies allow us to see vast potential of genome editing as a therapeutic strategy. It’s hard not to be thrilled and excited when you understand that progress of genome editing technologies can completely change our understanding of treatment of Parkinson’s disease and other neurodegenerative disorders,” she adds.

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FTC Warns Companies Against Unsubstantiated Advertising of CBD Products for Fibromyalgia

cannabis as medicine

The U.S. Federal Trade Commission (FTC) sent warning letters to three companies that sell cannabis-based products containing cannabidiol (CBD), cautioning them that making unsubstantiated claims about the health benefits of CBD could lead to legal action.

The agency “urges the companies to review all claims made for their products, including consumer testimonials, to ensure they are supported by competent and reliable scientific evidence,” according to a press release. The FTC also warned that continuing to sell CBD products without such evidence could violate the FTC Act and result in legal action.

The companies — which the FTC did not name — have been instructed to respond within 15 days to tell the agency what specific actions have been taken to address the FTC’s concerns.

“It is illegal to advertise that a product can prevent, treat, or cure human disease without competent and reliable scientific evidence to support such claims,” the agency warned in its letters.

CBD is one of the active compounds of the cannabis plant that has garnered interest in past years for the treatment of multiple health conditions. In contrast with other cannabis compounds, CBD has demonstrated to have anti-inflammatory and pain-relieving properties without any psychoactive effects.

Despite the therapeutic potential of cannabidiol, there is scarce scientific evidence effectively demonstrating the safety and benefits of CBD-based products. In most cases, there haven’t been enough well-controlled studies to make reliable scientific conclusions about CBD’s efficacy, or lack thereof.

According to the FTC, however, that has not stopped some companies — and these three in particular — from making unsubstantiated claims about the “benefits” of CBD.

The three companies to which letters were sent sell CBD-infused oils, tinctures, capsules, gummies, and creams. According to the FTC, all have advertised that their CBD products are able to cure or treat serious health conditions and diseases. Beyond relieving pain, the three companies claimed their products could treat arthritis, fibromyalgia, Parkinson’s disease, cancer, Alzheimer’s disease, amyotrophic lateral sclerosis (ALS), Crohn’s disease, psoriasis, and multiple sclerosis.

One company’s website claims that CBD “works like magic” to relieve “even the most agonizing pain,” suggesting that this pain-relieving effect is more powerful than that of prescription opioids, which include morphine and oxycodone. To support its claims the company states that it has worked with Harvard scientists through “thousands of hours of research.”

Another company described CBD as a “miracle pain remedy” for both acute and chronic pain. The third states that CBD gummies are highly effective at treating “the root cause of most major degenerative diseases,” and claims its CBD cream relieves arthritis pain and that its CBD oil may effectively treat epilepsy and other conditions.

There have been studies to suggest that CBD can relieve pain for some patients. However, the sweeping generalizations in these companies’ advertisements ignore many relevant caveats. Most studies on CBD were done in people with a serious disease, such as cancer, and they often include a small number of participants. Even in cases in which the study shows statistically significant changes, the positive impact tends to be modest, not allowing scientists to reliably say whether or not CBD is helpful in managing pain or other symptoms.

The FTC teamed up with the U.S. Food and Drug Administration (FDA) in March to sent similar joint warning letters to three other companies — Nutra Pure, PotNetwork Holdings, and Advanced Spine and Pain. Those letter, which raised similar concerns related to marketing CBD, also allowed the companies 15 days to take corrective action.

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Dopamine-Resistant Tremors Caused by Abnormal Brain Activity, Study Finds

Tremors

Parkinson’s patients whose tremors respond poorly to dopaminergic medications are likely experiencing abnormal brain activity outside the brain’s dopaminergic system, a study finds.

The results, “Cerebral differences between dopamine-resistant and dopamine-responsive Parkinson’s tremor,” were published in the journal Brain.

The main cause of motor symptoms in Parkinson’s disease is a lack of dopamine — a key brain chemical — resulting from a loss of dopaminergic neurons in the substantia nigra, a brain area responsible for controlling voluntary muscle movements. For that reason, levodopa, a dopamine replacement therapy, is often recommended to ease Parkinson’s symptoms.

“However, while dopaminergic medication effectively treats bradykinesia [slowness of movement] and rigidity, the effect on resting tremor is unpredictable and varies greatly between patients,” the researchers said.

“This observation casts doubt on the idea that Parkinson’s tremor has a dopaminergic basis,” they said.

One alternative explanation for the variability in treatment response is that tremors have different underlying causes depending on the patient. In some people, tremors indeed are caused by disturbances in the brain’s dopaminergic system — and for that reason, those patients respond well to dopaminergic medications. In other individuals, however, the tremors have a different underlying cause that these therapies are not able to tackle.

Researchers from the Donders Institute for Brain, Cognition and Behaviour, in the Netherlands, now set out to determine whether resting tremors that are resistant to dopaminergic medications are linked to abnormal brain activity in non-dopaminergic brain regions, such as the cerebellum, a region responsible for body balance.

To test this hypothesis, they first carried out a levodopa challenge, in which they administered the medication to 83 people with Parkinson’s who regularly experienced resting tremors. Their aim was to evaluate the patients’ response to the therapy.

After dosing, they selected the 20 participants who had the best treatment responses — tremors reduced by 71% after therapy — and the 14 patients who had the worst treatment responses. Those participants had their tremors reduced only by 6% after therapy.

Then, in the new subgroup of 34 patients with the best and worst responses to treatment, they used a technique called combined electromyography with functional magnetic resonance imaging (EMG-fMRI). That technique evaluated the participants’ tremor-related brain activity in two different settings: immediately after treatment with a placebo, or immediately after being treated with levodopa/benserazide combination therapy, administered at a dose of 50 or 200 mg.

Results showed that individuals whose tremors failed to respond to therapy had higher tremor-related brain activity in non-dopaminergic brain regions, including the cerebellum.

Conversely, in patients who had the best responses to treatment, analyses showed most tremor-related brain activity happened in dopaminergic brain regions. These regions included the thalamus, which regulates consciousness, sleep, and alertness, and the secondary somatosensory cortex, a region involved in pain processing.

In addition, researchers found that, in both groups, levodopa prevented abnormal brain activity associated with tremors in the thalamus. However, this protective effect was much stronger in people who responded well to dopaminergic medications compared with those who responded poorly to treatment.

“These results suggest that dopamine-resistant tremor may be explained by increased cerebellar and reduced somatosensory influences onto the cerebellar thalamus, making this region less susceptible to the inhibitory effects of dopamine,” the investigators said.

“These findings may have therapeutic implications, suggesting that an alteration of cerebellar reactivity and/or tremor-related processing may improve the clinical dopamine response of tremor,” they added.

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