I have been a huge Neil Diamond fan all my life, and I was upset when I heard the news that Neil would no longer be touring due to his fight against Parkinson's disease (PD). Parkinson’s has affected many people in my personal life; my late grandfather and my wife’s late grandfather both lived with PD, and several others close to us are battling the disease today.
One day, my brother-in-law asked me how much Neil Diamond music I had in my collection. I dragged all my tunes onto a playlist, and it came out to over 400 different songs and 24 hours of his work! "I am", I said, "a believer that 24 hours of Neil would be a perfect day." After thinking about this idea for a few years, we made the decision to hold a "Neil-a-thon" to raise money for the Parkinson's Foundation.
With a bunch of help from my family members, we held the first Neil-a-thon on July 29, 2023. The event started at 3 a.m. and we continuously played Mr. Diamond's songs until 3 a.m. the following day. To pass the time, we developed a menu that included a different little drink and snack for each of the 24 hours. The menu included items like "Song Sung Blueberry Muffins," "Holly Holy Guacamole," "Cherry, Cherry Cheesecake" and "Sweet (and Sour) Caroline Chicken."
Throughout the course of the day, friends and family dropped in, had fun, sang along and donated funds to the cause. Overall, we raised over $2,800 for the Parkinson's Foundation. We had so much fun that we aim to make this an annual event.
We hope that the funds can be used to support the fight against PD and help people with Parkinson’s live better lives. If our efforts could be used to support someone in need, we would all be able to say that we feel..."so good, so good, so good!"
Parkinson’s Foundation Presents 6 Findings at International Congress of Parkinson’s Disease and Movement Disorders®
Alongside the 10 million people around the world living with Parkinson’s disease (PD), there are neurologists, healthcare professionals, researchers and organizations who are dedicated to helping them. Every year, thousands of these professionals and researchers share their ideas to advance PD care and research at the International Congress of Parkinson’s Disease and Movement Disorders. This year the event was held in Copenhagen, Denmark in August 27 to 31.
Discover the six research findings the Parkinson’s Foundation shared at this year’s event below.
1. Informing People with Parkinson’s of Their Gene Variant Status: PD GENEration, a North American Observational and Registry Study
PD GENEration: Mapping the Future of Parkinson's Disease is a research study that offers genetic testing and counseling, in English and Spanish, to people with Parkinson’s. This study aims to simplify access to clinical genetic testing to people with Parkinson’s and will ultimately help accelerate clinical trials in PD.
Key Takeaways
The study has enrolled 10,510 participants from the U.S., Puerto Rico, Canada and the Dominican Republic.
12.7% of people with Parkinson’s who have completed PD GENEration testing have a genetic tie to Parkinson’s.
By providing genetic testing to those from all backgrounds, the study helps inform care, diversify the data, help engage people in research and qualify more for enrollment in clinical trials for PD.
2. Systematic Screening and Treatment of Depression in Parkinson’s within Movement Disorders Centers: A Quality Improvement Initiative
Depression is common in Parkinson’s disease and has a significant impact on quality of life.
A survey of clinicians at Parkinson’s Foundation Centers of Excellence revealed that most centers do not routinely screen for depression, and that the use of mental health professionals and antidepressants varies substantially, suggesting that clinical practice changes could improve care.
Key Takeaways:
Administering depression screening through the Geriatric Depression Scale-15 (GDS-15) is possible among Parkinson’s Foundation Centers of Excellence.
Time is a key barrier to administering formal depression screening.
Significant changes in the depression scale were observed, suggesting improvements in depressive symptoms through systematic depression screening.
This study demonstrates that depression screening among people with PD is feasible. By screening for depression, we can help detect, improve and treat depressive symptoms among people with PD.
3. Understanding Parkinson’s Patients' and Carepartners' Palliative Care Knowledge & Preferences
People with Parkinson’s and care partners have significant palliative care needs; however, little is known about their preferences and knowledge of palliative care. As part of a national project to implement outpatient palliative care across Centers of Excellence, we sought to better understand patient and family perceptions and knowledge of palliative care through interviews conducted across 15 Centers of Excellence.
Key Takeaways:
People with Parkinson’s and care partners:
Had varying levels of knowledge about palliative care. Some believed palliative care was about end-of-life, while others were unclear about the term and what it meant.
Said non-movement symptoms are the most challenging aspect of Parkinson’s and wanted neurologists to routinely assess and provide ways to manage these symptoms.
Felt that challenging emotions and spiritual needs were rarely addressed and want more support for these needs.
Notice gaps in the delivery of palliative care and want more education and support to address their palliative care needs.
4. An International Consensus Statement for Rehabilitation Care in Parkinson’s
Rehabilitation (including physical, occupational and speech therapy) plays a crucial role in improving PD symptoms and quality of life. However, rehabilitative care is under-recognized and under-utilized in PD and often only utilized in later disease stages, despite research showing its positive effects. Currently, there is a lack of consensus regarding rehabilitative services in PD. The Parkinson’s Foundation convened a task force to develop a consensus statement regarding the incorporation of multidisciplinary rehabilitation in PD care.
Key Takeaways:
Rehabilitative interventions should be an essential component in the treatment of PD, from diagnosis to advanced disease.
The consensus statement addresses fundamental components of rehabilitative care for PD and will help establish paradigms for the delivery of high-quality rehabilitative care for PD.
Rehabilitative care should be offered regularly throughout the disease course with repeat assessments and interventions adapted to changes in a person’s condition or needs.
5. Practice and Outcome Variation Across Parkinson’s Foundation Centers of Excellence
Parkinson’s Foundation Centers of Excellence are medical centers with a specialized team who are up to date on the latest PD medications, therapies and research to provide the best care. In this study, researchers examined the variation of care received from 12,664 participants with PD across 31 centers. To understand the relationship between practice and outcomes, next the researchers will identify treatment practices that are associated with better outcomes to help guide high quality clinical care.
Key Takeaways:
While Centers of Excellence provide excellent care, there remains substantial variation in treatment practices and outcomes, which may relate to the PD patient population and remains to be further explored.
Center patients who received a PD diagnosis within 5 years:
Dopamine agonist use varied between 0 and 80% of patients.
35% sent to physical therapy with 9 centers higher and 8 centers lower than average
22% had falls with 8 centers higher and 6 centers lower than average.
Center patients who received a PD diagnosis more than 5 years:
40% sent to physical therapy with 8 centers higher and 10 centers lower than average.
20% received DBS with 12 centers higher and 8 centers lower than the center average.
46% had falls with 7 centers higher and 8 centers lower than average.
6. Parkinson’s Team Training Is Beneficial for New and Established PD Centers
Parkinson’s Foundation Team Training educates care teams on proven PD care practices and how to maximize teamwork. The goal of the Team Training is to provide more coordinated and complete care to improve the quality of life of those living with PD and their caregivers. Team training participants completed surveys before, immediately after and six months after training to assess learning and the benefit of the program in providing care.
Key Takeaways:
Team Training was shown to have a positive impact on interprofessional team members of both community care and established PD centers.
Attendees were more confident in the care they provide to those with PD and care partners, increased their knowledge of the roles of other team members, and better understood their own roles within the PD care teams, allowing teams to work more effectively together to provide better care.
Better care translates to improving the quality of life for those living with PD.
Developing Cutting-Edge Tools to Control and Study Dopamine Signaling
The biological hallmark of Parkinson’s disease (PD) is the progressive loss of dopamine neurons in the brain. In healthy neurons, the neurotransmitter dopamine and its receptors are carefully regulated and transported to facilitate motor function. Many PD-related mutations affect this regulation, but it has been difficult for researchers to fully investigate these complex processes without more sophisticated methods. Chelsie Kadgien, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, has developed and will be testing novel research tools that will allow her to not just study dopamine signaling in greater detail, but to manipulate it and track the effects in real time as well.
Working with her mentors Dr. Matthew J. Kennedy and Dr. Christopher P. Ford at the University of Colorado Anschutz Medical Campus, Dr. Kadgien has created two different methods to control and investigate dopamine signaling in mouse brains. The first method involves reprogramming neurons to produce small proteins called “nanobodies” that bind to dopamine receptors. These nanobodies stick to dopamine receptors right after they are formed inside the cell and prevent them from being shuttled to the cell surface where they are needed, leading to a reduction in dopamine reception — similar to what is caused by certain PD mutations.
Dr. Kadgien can also release the nanobodies from the inside of the cell chemically, allowing her to control when dopamine reception is turned back on and by how much. This will provide insight into how therapies that restore dopamine receptor levels could be used for people with PD.
The second tool that will be tested involves optogenetics, the use of genetically engineered compounds that can be triggered by light. Dr. Kadgien has designed a light-controlled neurotoxin that prevents the release of dopamine from brain cells, mimicking how PD mutations can prevent dopamine signaling. Not only is this neurotoxin activated by light, but it is also reversible. When left in the dark for eight hours, the toxin’s effects wear off and dopamine release is restored. This powerful tool will allow Dr. Kadgien to study dopamine signaling impairments and restoration in a wide range of ways that have never been possible before.
By testing and refining both dopamine pathway manipulation methods, Dr. Kadgien will lead the way for future research into PD therapies that can best restore dopamine signaling and improve the lives of people living with PD. Speaking on what this award means to her, Dr. Kadgien said “I am incredibly honored to be selected for this award amongst many talented peers … [This research] will build the foundation for my career studying how disruptions in communication between brain cells can lead to Parkinson's disease. I hope my work will lead to improvements in quality of life for people living with the disease and their families.”
Developing a Drug Screening Platform to Identify Inhibitors for Different Alpha-synuclein Strains
While every person with Parkinson’s disease (PD) experiences unique symptoms and progression, all people with PD have a protein in their brain called alpha-synuclein that is not working like it should. Recent studies have shown that each person with PD may have a unique misfolded version of this protein, which may be related to disease severity.
From his lab at Johns Hopkins University in Baltimore, MD, Dr. Gadhave’s research is dedicated to developing an alpha-synuclein strain screening assay that will help to identify inhibitors for different variants, or strains, of misfolded alpha-synuclein.
With the help of his mentor Xiaobo Mao, PhD, Dr. Gadhave has already identified key inhibitors. Dr. Gadhave will use these inhibitors for screening alpha-synuclein proteins from spinal fluid samples of people with PD.
What are Lewy bodies? Lewy bodies are toxic aggregations, or clumps, of alpha synuclein that affect chemicals in the brain, leading to problems with thinking, movement, behavior and mood.
The identified compounds that bind to misfolded alpha-synuclein may also be able to inhibit the formation of Lewy bodies, which are strongly linked to PD. The second half of Dr. Gadhave’s research will test whether the compounds found to bind specific alpha-synuclein strains can slow PD from advancing. This research could lead to the generation of personalized PD therapies that use inhibitors capable of counteracting a unique alpha-synuclein strain.
Dr. Gadhave believes this research can improve how we treat Parkinson’s. “Completing this research will lead to the development of a new compounds for alpha-synuclein strains, which will benefit the therapeutic development for PD.”
Deciphering gait signaling to improve movement therapies
The metaphor of “a walk in the park” implies that something is simple and easy; however, the neuroscience involved in such an activity is incredibly complex and relatively unstudied. This complexity is most evident in the context of movement disorders such as Parkinson’s disease (PD), where current therapies struggle to address the movement issues associated with the condition. Rodrigo Manuel Paz, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, has homed in on a specific region of the brain crucial for walking and will be devoting his research to better understanding how it works and how novel therapies can better treat trouble moving or walking in people with PD.
Dr. Paz is particularly interested in the brain’s way of managing gait, the repeating pattern of coordinated muscle activity associated with walking. In PD, gait impairment leads to loss of balance and risk of falling, as the brain struggles to maintain a consistent walking rhythm.
Working alongside his mentor, Dr. Alexandra Nelson at University of California San Francisco, Dr. Paz plans to investigate how gait may be regulated by the motor thalamus region of the brain. The motor thalamus receives signals from the basal ganglia, a neuron hub which contains the dopamine neurons that are lost in PD, and relays those signals to the motor cortex, which ultimately communicates the movement command to the muscles.
Dr. Paz will use mice in his experiments, comparing those with PD-like neurodegeneration to those without such neuron loss. A device will be attached to the mice that allows Dr. Paz to measure the activation of motor thalamus neurons as the mice walk freely, while high-speed cameras capture and correlate those activations to their gait. These data will provide insight into how the motor thalamus neuron activity may connect to walking coordination and whether such activity is impaired in PD-like mice, contributing to movement dysfunction.
Next, Dr. Paz will use brain slices from mice with and without PD-like neurodegeneration to better understand the mechanistic changes that may be occurring between the motor thalamus and its associated brain regions. Using optogenetics — a technique by which light can be used to trigger genetically-altered cells — he will stimulate neurons from the basal ganglia and motor cortex to watch and calculate motor thalamus responses and determine how neurodegeneration affects that important communication pathway in the brain.
Dr. Paz is enthusiastic about what such results may mean for future therapies. “By understanding how motor thalamus influences gait and how changes in synaptic inputs drive impaired gait signals in motor thalamus, this project will establish a fundamental framework for improving therapies specifically aimed at alleviating gait deficits in people with PD,” he said.
Uncovering how an alternative mitochondria cleanup process may reduce brain inflammation
Inflammation is the body’s way of dealing with unwanted invaders, mobilizing immune cells to contain, destroy, and clean up areas of infection or injury. However, this process sometimes malfunctions, leading to cell and tissue damage. There is evidence to suggest that such inflammation misfires occur in Parkinson’s disease (PD) and may be contributing to neuron degeneration; however, the source of these potential inflammatory errors has not yet been identified. Tahnee Saunders, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, believes that answer may lie in mitochondria, the powerhouses of the cell.
Mitochondria are organelles, or “mini organs,” found in nearly all cells that use oxygen to power numerous critical biological processes. Like any other hard-working engines, mitochondria eventually get worn out and may break down, requiring disposal by the cell in a process called mitophagy (from the Latin “phagus”, meaning “to eat”) that involves the proteins PINK1 and Parkin. In some cases of young-onset PD, those two mitophagy proteins are dysfunctional, preventing the disposal of broken mitochondria and potentially contributing to increased inflammation and neurodegeneration.
Dr. Saunders, working with her colleagues in the lab of Associate Professor Michael Lazarou at the Walter and Eliza Hall Institute in Victoria, Australia, will be investigating a new form of mitophagy that may hold therapeutic promise for those with PD involving mitochondrial damage. This form of mitophagy occurs when the inner mitochondrial membrane (IMM) becomes exposed and is used to start the disposal chain reaction independent of PINK1 and Parkin. Using cells from both PD-model mice and from people with PD, Dr. Saunders will define the key factors driving IMM-induced mitophagy while also exploring the prevalence of this pathway in different cell types found in the brain.
With the knowledge gained from this research, novel therapies may be developed that boost IMM-induced mitophagy in the brains of those with PD, including individuals with PINK1 or Parkin deficiencies, potentially reducing inflammation and consequent neuron loss. Such therapies could one day be life-changing to those with PD, slowing or even stopping the progression of the disease.
When asked what this Parkinson’s Foundation grant award means to her, Dr. Saunders said it “has been a huge validation of the work I am doing and has given me a clear vision for my future research into Parkinson’s disease…I feel extremely passionate about helping those living with Parkinson’s.”
Episode 156: Research Series: Expanding PD GENEration
Variants of several genes have been identified that raise the risk of developing Parkinson’s disease (PD). PD GENEration: Mapping the Future of Parkinson’s Disease is the Parkinson’s Foundation groundbreaking initiative that seeks to uncover the relationship between genetics and one’s risk for PD. The goal is to eventually help people better manage their disease, facilitate research into better treatments, and potentially, find a cure. The study is now expanding to actively enroll people of diverse backgrounds. Variants of certain genes associated with the risk of developing PD have different frequencies among different populations. Besides reaching out to Black and Asian communities in the mainland United States, PD GENEration is now expanding to Hispanic communities in Puerto Rico as well as in the Dominican Republic (DR).
Although every person’s disease is unique to them, understanding genetic differences across broad groups of people may help explain why a person’s experience with the disease differs from others. That is why it is important for PD GENEration to enroll people from diverse communities, where genes associated with the disease may occur at different frequencies.
Our guest in this episode is Amasi Kumeh, Director of Research Partnership at the Parkinson’s Foundation. She explains why it is important to include people of diverse backgrounds in the study and how and where the Foundation is reaching out to enroll people from a diverse range of communities in PD GENEration.
Released: August 8, 2023
Amasi Kumeh is the Director of Research Partnerships at the Parkinson's Foundation. She has worked in various capacities in the Parkinson's research sector for over ten years. She has experience as a global business process and program management expert for collaborative pre-clinical and clinical research projects related to Parkinson's disease. She is passionate about inclusivity and diversity in Parkinson's research to improve life for all people with Parkinson's and their family members. She currently spearheads a Foundation initiative to expand Parkinson's research into diverse communities and is responsible for cultivating industry partnerships to leverage the Foundation's rich data assets and increase investments in their flagship clinical programs.
Untangling the connections between inflammation, aging and Parkinson’s disease
Inflammation is a process that occurs in the body as a response to a threat (e.g., an injury or a wound). However, the body’s ability to wind down the response after the threat has passed decreases as the body ages. This results in a consistent low-level, age-related inflammation known as “inflammaging” that is thought to weaken cells and tissues, including the brain. As aging is the greatest risk factor for Parkinson’s disease (PD), many have hypothesized that inflammaging plays a role in the development and progression of the disease. The details and mechanisms behind such a connection have remained a mystery, but Sarah Talley, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship for Basic Scientists, is hoping to shed some light on the subject.
Dr. Talley, working in the lab of Dr. Edward Campbell at the Loyola University Medical Center in Chicago, IL, seeks to understand how inflammaging may exacerbate the spread of alpha-synuclein clumps in the brain. These tangled-up alpha-synuclein proteins have been directly associated with PD, causing progressive neurodegeneration as they spread from cell to cell. It has also been shown that mice experience inflammaging like humans, making them the model of choice for Dr. Talley’s research.
What is inflammaging? Inflammaging refers to consistent inflammation that
increases as a person ages. It can weaken cells and tissues, including the brain, and may play a role in PD progression.
The key to these experiments is a genetically modified mouse line, previously generated by Dr. Talley and her fellow researchers, in which key cell types in the brain light up when experiencing inflammation. This light – bioluminescence, more specifically – can be measured and quantified under a high-powered microscope, allowing Dr. Talley to quantify inflammation in different brain cell types over time. With sophisticated cranial window imaging techniques, she will be able to make these measurements while the mice are still alive, providing valuable data over time.
Dr. Talley will inject alpha-synuclein tangles into the brains of these mice and monitor how those tangles spread and cause damage in the brain over time, but also how that spread affects brain-wide inflammation. By conducting these experiments in both young (6-week-old) and old (18-month-old) mice, Dr. Talley will be able to compare inflammation changes and alpha-synuclein spread between the age groups.
Dr. Talley, excited for the chance to start this research with the support of the Parkinson’s Foundation, spoke to the significance of this project: “We finally have the tools in place to measure when and where inflammation occurs in the [brain] during Parkinson's disease development in mouse models of the disease… These experiments will provide foundational knowledge that can inform on when and where anti-inflammatory therapeutics could be used to remedy disease in PD patients."
Highlighting the Connections between Parkinson's, Immune Responses and the Gut
It is becoming clear that gut and brain health are intrinsically connected. This connection is referred to as the “gut-brain axis.” Parkinson’s disease (PD) is no exception. Several studies highlight how gastrointestinal issues, such as constipation, commonly show up before movement symptoms when it comes to PD — often by years or decades. While the pathways linking gut health specifically to PD progression are still unknown, Juliet Taylor, PhD, and recipient of a Parkinson’s Foundation Impact Award, believes that an important element involved is type-I interferon (IFN) signaling, a part of the body’s immune response toolkit.
From her lab at the University of Melbourne in Parkville, Australia, Dr. Taylor seeks to understand how early IFN disturbances in the gut may lead to later PD development, and whether affecting such signaling can slow or prevent overall disease progression.
Meet IFN. Even those well-versed in Parkinson’s may not be familiar with type-I interferon (IFN) receptors. IFN’s help the body fight infection. Parkinson’s Foundation researcher, Juliet Taylor, is investigating whether IFN issues in the gut may lead to later PD development, and whether affecting signaling can slow or prevent overall disease progression.
IFN proteins are secreted by white blood cells, often in response to infections to stimulate immune responses. The ability of IFNs to quickly drive the body to fight back against invaders has its risks, however, since prolonged or improper IFN signaling can cause major stress and damage to cells and organs. IFN regulation has been shown to be critical in the gut, where the intestinal walls constantly encounter and prevent infection by microbes.
Dr. Taylor and her team have recently discovered that lab-created gut organoids — three-dimensional collections of gut cells that can be used to mimic live tissue — injected with PD-associated alpha-synuclein clusters (the protein associated with PD) show increased IFN production. To better understand this immune reaction to alpha-synuclein in the gut, Dr. Taylor will create variations of gut organoids with and without IFN signaling receptors and see how they react to alpha-synuclein exposure, helping to determine which gut cell types are most important in the response.
Next, Dr. Taylor will examine how alpha-synuclein injected into the gastric (gut) walls of young and old mice affects overall gastrointestinal health as well as how it may spread to the brain to cause PD-like neurodegeneration and movement symptoms. She will also use genetically engineered mice that lack the IFN-receptors to further explore how that pathway is associated with PD progression along the gut-brain axis.
Speaking on how the Parkinson’s Foundation award will support her lab’s research goals, Dr. Taylor said, “While the majority of research has focused on the brain pathology and associated motor symptoms in PD, there is increasing interest in the non-central nervous system effects of the disease, specifically the gut dysfunction experienced in many patients’ years earlier… The studies supported by this funding will develop a model within our laboratory that will potentially identify a novel modulator of the gut-brain axis in PD and therefore pave the way for future studies.”
Episode 155: The Evolution of the Parkinson’s Foundation Hospital Care Initiative
Of the one million people living with Parkinson’s disease (PD) in the United States, nearly one-third of them will have a hospital encounter each year. When hospitalized, three out of four people with PD will not receive their medications on time, possibly leading to worsening symptoms, medical emergencies, and a significantly increased length of stay, greatly increasing costs to the medical system overall.
To address this problem, the Parkinson’s Foundation developed key tools and resources for patients and providers as part of our Hospital Care Recommendations. Today’s guest, Peter Pronovost, MD, PhD, a major force in advancing hospital safety, helped develop these recommendations for making hospitals safer for people with PD, which includes standards of care. Dr. Pronovost practices critical care medicine and is Chief Quality Officer and Chief Clinical Transformation Officer at University Hospitals in Cleveland, Ohio.
Released: July 25, 2023
Peter Pronovost, MD, PhD, is a world-renowned patient safety champion, physician executive, critical care physician, prolific researcher with more than 1000 peer-reviewed publications, an innovator who has founded several technology companies, and a thought leader informing U.S. and global health policy.
Dr. Pronovost’s transformative work leveraging checklists to reduce central line-associated bloodstream infections has saved thousands of lives and earned him national acclaim. This life-saving intervention has been implemented across the U.S., and as a result, central line-associated infections that used to kill as many people as breast or prostate cancer have been reduced by 80 percent. In recognition of this innovation, his highest-profile accolades include being named one of the 100 most influential people in the world by Time Magazine and receiving a coveted MacArthur Foundation “genius grant.”
While serving as Chief Clinical Transformation Officer at University Hospitals Health System in Cleveland and as a Professor in the Schools of Medicine, Nursing and Management at Case Western Reserve University, Dr. Pronovost developed a checklist to make visible defects in value and deployed a management and accountability system to eliminate those defects.
This system reduced the annual cost of care for Medicare patients by 30% over three years while improving quality. In 2022, Dr. Pronovost lead the efforts that culminated in University Hospitals winning the American Hospital Association’s Quest for Quality award, the industry’s most prestigious honor recognizing its member organizations for their commitment to quality. He was named the Veale Distinguished Chair in Leadership and Clinical Transformation in 2023.
