Over the past few years, Parkinson's disease (PD) research has undergone a dramatic transformation. Scientists are moving beyond the traditional focus on the brain alone and adopting a whole systems approach to understanding the disease. Today, research is looking at the interconnected roles of the brain, gut, inflammation, genetics and environmental factors in the development and progression of PD.
Advancements in artificial intelligence (AI) are also playing a key role, helping researchers analyze vast amounts of data to uncover new insights and potential therapies.
In this Neuro Talk update, join James Beck, PhD, Chief Scientific Officer at the Parkinson's Foundation, as he discusses this evolution in Parkinson’s research and what this could mean for the future of those living with PD.
Episode 174: The Evolution of PD GENEration for Genetic Testing & Counseling
The Parkinson’s Foundation makes life better for people with Parkinson’s disease (PD) by improving care and advancing research toward a cure. The Foundation recognizes the importance of funding and supporting research studies dedicated to better understanding the causes of PD, developing more effective treatments, and ultimately finding a cure. The Foundation awards research grants to support investigators working on diverse research projects, along with collaborating with other institutions to advance PD research.
One of its major initiatives is exploring the genes and other factors associated with the development of PD through a global project, PD GENEration: Mapping the Future of Parkinson’s Disease. By gathering genetic information from tens of thousands of people with PD, this study offers genetic testing for relevant disease-related genes and genetic counseling to help participants understand their results, all at no cost to them. At the same time, knowledge gathered through PD GENEration will promote more focused, gene-specific clinical trials of drugs and may lead to novel therapy options for people with PD. In this episode, we explore the origins of PD GENEration, its growth over the years, and its goals with Dr. James Beck, Chief Scientific Officer of the Parkinson’s Foundation.
Released: December 31, 2024
As Chief Scientific Officer, James Beck, PhD, sets the strategic direction for the Parkinson’s Foundation research vision. Dr. Beck oversees a portfolio that has guided more than $400 million in research to explore what causes Parkinson’s disease (PD) and how to improve treatments, working towards a world without Parkinson’s disease. He has played an integral role in positioning the organization as a world leader in accelerating Parkinson’s research.
Dr. Beck launched PD GENEration: Mapping the Future of Parkinson's Disease, a national study started by the Parkinson’s Foundation in 2019 that offers genetic testing for Parkinson’s-related genes and genetic counseling at no cost for participants with a confirmed PD diagnosis. Additionally, he led the team that updated the estimated prevalence of PD in the U.S. and globally and collaborated with several organizations to develop the economic burden of Parkinson’s disease.
Improving Parkinson’s Outcomes: Harnessing AI to Evolve Care & Diagnosis
Nami Shah, MD, is passionate about improving in-hospital and outpatient care for people with Parkinson’s disease (PD). As a Parkinson’s Foundation Wesley G. McCain Movement Disorders Fellow at the University of Rochester Medical Center, a Parkinson’s Foundation Center of Excellence, she is examining how electronic medical record alerts can reduce medication errors during hospital stays.
Dr. Shah is also part of a study evaluating how AI-technology can identify Parkinson’s symptoms and eventually aid in the diagnosis of PD. And, she is a sub-investigator for a qualitative interview study on freezing of gait.
We spoke to Dr. Shah about her exciting work in the PD field, and how working with the Parkinson’s community inspires her.
"I'm so grateful to have the support of the Parkinson's Foundation. It's critical to have a foundation like this invested in supporting Parkinson's research and in improving care."
- Nami Shah, MD
What led you to Parkinson’s research?
Toward the end of my neurology training, I spent a couple weeks rotating through the movement disorders clinic at the University of Rochester, and that really solidified my decision to not only go into movement disorders and work with patients with Parkinson’s, but to also do research in that area. It was a humbling experience to give a diagnosis of Parkinson’s disease, and to hear patient stories about dealing with the disease each day and during hospitalizations.
Sometimes patients told me stories about their great care experiences, and the not great experiences too. These stories are what increased my interest in doing research that primarily focuses on trying to improve care for patients with Parkinson’s in the hospital setting and improving some of the tools used in research, so they better reflect what is important to patients and their actual experience with the disease.
How has this fellowship impacted your career?
It’s been critical to my training. When I completed my neurology residency, I received some basic training in how to take care of patients with Parkinson’s and identify that they have the disease, but this fellowship has really made me appreciate the nuances of Parkinson’s. It has given me confidence in my ability to diagnose Parkinson’s and differentiate it from related disorders.
How are you helping reduce medication errors in hospital settings for people living with Parkinson’s?
I've been working on this project for over a year now, and we're almost done analyzing results. A group of researchers, before my time, introduced a best practice advisory —an electronic medical alert that is triggered when patients carry a diagnosis of Parkinson's. So, if someone with Parkinson’s is admitted to the hospital and a provider tries to order a contraindicated medication, the alert tells the provider to think about the risk versus benefit of ordering that medication. My part in the project was to look at how this warning system impacted hospital stays and affected the rate of complications.
Advocate for your best care when in the hospital for an unplanned visit
The initial analysis shows that it really does have an impact. Not only did the warning system drastically reduce the number of orders of that kind, but it also showed increases in length of stay for patients when they received these contraindicated medications. I think it's promising because it's such a simple intervention, but it can really make a difference for patients with Parkinson’s during hospital stays.
I'm also working on designing an order set that makes it easier to identify and order time-sensitive medications for patients with Parkinson’s in the hospital. The hope is to make this process easier for providers, especially those who are not as familiar with Parkinson's, and to decrease the risk of increased rigidity, falls, and swallowing difficulties that patients can experience due to delays in administration of these medications.
Can you explain your research on how AI can help identify symptoms and diagnose PD?
This is still in the early stages, but I think it is exciting to involve AI in Parkinson’s diagnosis. The study I am involved in is having us code patient videos to identify important symptoms that lead to a Parkinson’s diagnosis. The goal is to use this information to train AI technology so it can help with diagnosis and maybe use it as an alerting technique for providers who may not be as familiar with Parkinson’s.
Are you working on any other Parkinson’s research?
I am serving as a sub-investigator for a qualitative interview study that utilizes novel symptom mapping techniques to evaluate meaningfulness of a novel Freezing of Gait Patient Reported Outcome Assessment, developed by an international consortium of specialists.
This study is looking at using a symptom mapping technique to illuminate symptoms of importance and interest to patients with Parkinson’s, particularly how they experience freezing of gait. Once we create the map of symptoms, we’re using that to assess whether a specific patient-related outcome measure that has been created in this group is appropriate, whether it is identifying the right symptoms for freezing of gait and whether it accurately reflects the patient experience. The goal is to determine if this tool is good, and if it is good, use it in future research studies to assess therapies that might be curative.
What gives you the greatest hope regarding your Parkinson’s-related work?
The people with Parkinson’s that I work with in the clinic and in my research projects inspire me. Not only are they incredibly brave when dealing with the daily challenges that Parkinson’s brings, they are also so generous with their time and willingness to help in research that would benefit others in the future. If they weren’t so kind or willing to participate, Parkinson’s care would not have advanced as much as it has.
Every day, researchers are working hard to identify the mechanisms in the brain that are responsible for Parkinson’s disease (PD) and its symptoms. In 2024, scientists gathered even more information to help us solve this disease.
Our Science News article series highlight exciting Parkinson’s studies and how they impact those living with this disease. Explore our top Science News articles of 2024 below:
When diagnosing Parkinson’s doctors focus on symptoms since there is no single test that can diagnose Parkinson’s. This can result in a delay of diagnosis as early symptoms are often hard to distinguish as PD. This study investigated whether a skin test could help diagnose Parkinson’s earlier.
In Parkinson’s, the protein alpha-synuclein clumps in the brain, which is also referred to as phosphorylated alpha-synuclein (P-SYN). This study found that P-SYN could also be detected in the nerve cells in the skin. The amount of P-SYN in the skin could also be connected with the severity of a person’s symptoms.
In Parkinson’s, the dysfunction of the mitochondria is one of the causes of the death of neurons in the brains. This study was the first to discover a receptor called GUCY2C, which could lead to a potential new way to fight dopamine loss.
Researchers found that the loss of GUCY2C led to dysfunction of mitochondria and cell loss in the part of the brain affected by PD. GUCY2C was found as a defense to protect dopamine neurons in the brain. This new discovery could lead researchers to explore the possibility of stimulating GUCY2C as a treatment for PD.
Movement symptoms associated with Parkinson’s often impact quality of life. A study found that the non-invasive treatment option called a focused ultrasound helps relieve tremors, improve mobility and other movement symptoms related to PD.
In this study, the focused ultrasound treatment targeted the part of the brain that controls movement. Nearly 70% of participants in the treatment group responded successfully to treatment after three months of follow-up.
Plastic waste is a rising problem, especially as it breaks down into tiny pieces. This study observed that these tiny pieces may be an environmental risk factor for developing Parkinson’s.
Parkinson’s is diagnosed when the protein alpha-synuclein starts to accumulate in neurons in the brain. Through various experiments, this study found that polystyrene nanoparticles can interact with alpha-synuclein and promote its clumping formations — meaning plastic waste may be contributing to Parkinson’s as an environmental factor.
Deep brain stimulation (DBS) is a surgical therapy used to treat certain aspects of Parkinson’s. PD symptoms vary throughout the day, which can make DBS ineffective whether it's too much or too little.
This study used a clinical trial enrolled four participants to test a surgical treatment called adaptive DBS that detects and responds to brain activity to provide individualized and customized stimulation to help with Parkinson’s symptoms.
A hallmark of Parkinson's is the death of brain cells called dopaminergic neurons in a part of the brain called the substantia nigra. For people with Parkinson’s, these neurons stop producing dopamine, which helps control the body's movements and moods. However, it’s not clear if other types of cells are also affected.
This study identified a new type of neuron associated with Parkinson’s. By looking at which genes were turned on and off in hundreds of thousands of different cells in the substantia nigra, the researchers developed an “atlas of gene expression.” This research may help us better understand Parkinson’s, and possibly help guide the development of new treatments.
Even though up to 50% of people with Parkinson’s experience some form of depression, when it comes to PD mental health care, symptoms like depression are often overlooked. This study showed that introducing a five-minute questionnaire — the 15-question Geriatric Depression Scale (GDS-15) — to movement disorder clinics can improve the rate of depression screening and follow-up care for people with Parkinson’s.
The screening is a helpful way to detect in depression in people with Parkinson’s, which can help in finding suitable treatment earlier.
PRODUODOPA (available in Europe), also known as VYALEV (approved by the U.S. Food and Drug Administration on October 17, 2024), is a new Parkinson’s drug delivered continuously via a pump, like insulin pumps used for people with diabetes. Clinical trials show that it can be an effective option for those whose medications are wearing off or who may have dyskinesia.
This study covers the recent findings of the clinical trials completed in Europe evaluating the safety and effectiveness of this new formulation of levodopa (foslevodopa/foscarbidopa).
Investigating the Link Between Parkinson’s, Genetics and the Immune System
For decades, we have known that inflammatory changes occur in the brain of people with Parkinson’s disease (PD). But in the last few years, inflammation has been studied as a possible cause of the progressive nature of the disease and not just a result of it.
Catherine (Chi) Weindel, PhD, is studying this connection, specifically focusing on how one variant or mutation of the Parkinson’s disease-linked gene LRRK2 impacts immune health. She hopes this research will pave the way for a deeper understanding of how Parkinson’s starts and progresses, along with avenues for potential new therapies.
LRRK2 and PD
The LRRK2 gene plays a role in about 1% of all people with PD and 5% of those with a family history. LRRK2 variants are autosomal dominant — this means that inheriting only a single mutated copy of a gene from one parent can potentially lead to disease. Mutations in LRRK2 can result in the enzyme becoming overly active in the brain, leading to cell death in ways we do not yet fully understand.
“My research involves the study of the immune system. What I am interested in is determining how the immune system might be different in people with Parkinson’s genetic mutations, which would cause a difference during an infection or in response to an environmental toxin,” said Dr. Weindel. “I am studying how alterations or modulations in an immune response could build up over time, piece by piece, and might predispose someone to develop Parkinson’s later in life.”
When Dr. Weindel first began investigating Parkinson’s, she suspected that immune system inflammation, triggered by illnesses and loss of dopamine neurons outside the brain, could ultimately lead to the development of the disease. This line of thinking led to her Parkinson’s Foundation Postdoctoral Fellowship, where she designed a study to explore how a LRRK2 G2019S mutation may impact mitochondria, which provide energy for a cell, when immune cells have been stressed by infection.
She discovered that during an infection, when immune cells with LRRK2 mutations die, they uniquely increase inflammation that promotes the spread of bacteria throughout the body. This cell death seems similar to what researchers find in brains of people and mice with PD.
As a 2022 Parkinson’s Foundation Launch Award recipient, Dr. Weindel is taking her research a step further to gain a deeper understanding of how LRRK2 gene mutations cause cell death in immune cells in the brain. This will lead to the identification of new targets for Parkinson’s therapy that may better control inflammation, for instance. Her research will also help design improved genetic tests to give families with a history of Parkinson’s better insight into their risk for developing PD.
According to Dr. Weindel, genetics research is vital to understanding the connection between Parkinson’s disease and the immune system’s response because even when family members have the same PD mutation, the disease may present itself differently in each person. By looking at complex genetic interactions, we can see alternative pathways impacting specific individuals, which can dictate better clinical trials or potential therapies.
“My goal is to develop therapeutics that will allow for a more personalized medical approach,” Dr. Weindel said. “Because Parkinson’s is such a diverse disease, a cure-all is very unlikely. Ideally, a particular therapeutic can one day be designed for an individual based on the genetic makeup of their Parkinson’s.”
2024 was a notable year for the Parkinson’s Foundation. It was 365 days of advancing research, listening to inspiring stories and forming deeper connections with people living with Parkinson’s disease (PD), their families, care teams and researchers.
With your support, we amplified our commitment to connecting more people to critical PD resources, expanding life-changing research and building a stronger, more inclusive network for those navigating Parkinson’s.
Thanks to YOU, here are the top 12 ways we made a difference this year:
In 2024, PD GENEration: Mapping the Future of Parkinson’s Disease expanded to new countries. We moved our genetics study into its next phase with support from the Global Parkinson's Genetics Program (GP2), a program of the Aligning Science Across Parkinson's (ASAP). This funding allowed us to expand recruitment and reach more people across the U.S., Canada, Latin America, South America and beyond.
Provided genetic testing and counseling to 17,944 people with Parkinson’s, at no cost.
Approximately 13% of people with Parkinson’s have a genetic link to the disease.
77% of participants have never participated in a research study before.
Additionally, PD GENEration began using a new, enhanced genetic test. We went from identifying seven PD-related genes to whole genome sequencing, which provides researchers with the most comprehensive data to study the genetics behind PD.
In 2024, we awarded nearly $3 million in research grants to 33 scientists conducting high-risk projects that do not typically receive federal funding. These are the kinds of projects that explore original approaches to care and propose new treatment ideas.
Understanding how depression and PD overlap in the brain is the focus of Dr. Ruhe’s Foundation-funded research. Over the next few years, he will work to identify the connections between depression and PD, which could uncover new treatments for both.
Each year, more than 300,000 people with Parkinson’s are hospitalized in the U.S. In 2024, we led the national effort to improve hospital care for Parkinson’s through systemic change. Our Hospital Care Initiative aims to help people with PD receive more reliable hospital care. To drive the change, we published a new Hospital Safety Guide for the community, distributing over 18,000 copies at no cost — and Hospital Care Recommendations for healthcare professionals.
In 2024, President Biden signed the National Parkinson's Project into law. This is the first-ever federal legislation dedicated to ending Parkinson’s. Here are some ways this monumental bill can make an impact:
Dramatically increase federal research funding
Develop more effective pathways for treatments and cures
Improve early diagnosis
Spark new and improved models for patient care
Address health disparities in diagnosis, treatment and clinical trial participation
In 2025 and beyond, the Parkinson’s Foundation is excited and honored to advocate for the PD community to help this new law create meaningful change.
We awarded more than $1 million in community grants for programs that help people living with PD in 40 states. Every health and wellness program we fund helps people live better with PD — from Rock Steady boxing and dancing classes to support groups. Since 2011, the Foundation has devoted more than $11.5 million in 879 community-based programs.
Pictured: Parkinson’s Foundation Community Grantee, San Francisco Ballet School offers free weekly classes, social gatherings, tickets to ballet performances, dance education and more. Read Cecelia’s story now
To find your nearest exercise or wellness class, visit your local chapter’s webpage or call our Helpline at 1-800-4PD-INFO (1-800-473-4636).
Thanks to our amazing supporters, our Reach Further fundraising campaign exceeded its goal early. In just three years, we raised $38.4 million to accelerate progress in Parkinson’s research, improve care and increase access to quality-of-life programs.
Throughout April we brought awareness to the #ABCsofPD, highlighting the most pressing Parkinson’s symptoms and topics. On April 2, 2024, we had the opportunity to ring the Nasdaq closing bell for Parkinson's Awareness Month. Opportunities like this are an impactful way we can reach more people and shine a light on the 10 million people living with PD worldwide.
On April 18, 2024, the producing team behind the Broadway hit, A Beautiful Noise: The Neil Diamond Musical presented $750,000 to the Parkinson’s Foundation in honor of legendary singer, songwriter and performer Neil Diamond, who is living with Parkinson’s.
We believe in spreading Parkinson’s Awareness year-round through steadily releasing new blog articles, podcast episodes, resources and interacting with our incredible community through social media.
8. Reached 1 million visits to our new Spanish PD pages
Hispanic and Latino members of the PD community often face distinct barriers to living well with Parkinson’s. Guided by our Spanish Advisory Group, we continue to develop educational opportunities and new resources for the greater Spanish-speaking Parkinson’s community. In 2024, our more than 50 Spanish pages on Parkinson.org reached 1 million visits. This information is not only reaching those who need them, but helping spread Parkinson’s awareness all over the world.
Volunteers are essential to our mission, helping us with outreach and representing us at local events. This year, we trained 232 Parkinson’s Foundation Ambassadors, who completed 195 presentations and reached 7,000 people.
Darrell Allers is a Parkinson’s Foundation Ambassador whose diagnosis eventually led him to volunteering, helping educate his community about Parkinson’s. Read his story.
We continue to provide early-stage funding for compounds that have the potential to become Parkinson’s drugs through our drug discovery and development initiative, Parkinson’s Virtual Biotech. Together with Parkinson's UK, we’re funding studies developing new, PD medications in years, not decades.
11. 20,000 participants raised more than $8.3 million through community fundraising events
Parkinson’s Foundation community fundraisers raised an impressive $8.3 million to advance PD research, access to care and life-changing resources in 2024. Together, every Moving Day, A Walk for Parkinson’s, walker, Parkinson’s Champion fundraiser and Parkinson’s Revolution rider brought us closer to a cure.
Peggy Farber joined Parkinson’s Champions to team up with other athletes with PD and be part of a louder voice in raising awareness. Read her story.
In November for National Family Caregivers Month, we highlighted the importance of caregiver well-being through addressing the challenges of burnout. We connected more people to support and resources that highlight the importance of self-care initiatives aimed to empower care partners.
Caregiver burnout is a state of physical, emotional and mental exhaustion experienced by individuals who care for others, typically family members or loved ones, who are unable to care for themselves.
How does the Parkinson’s Foundation genetics study, PD GENEration: Mapping the Future of Parkinson’s Disease, help people with Parkinson’s? What’s next for the study? Why should people with Parkinson’s consider enrolling?
Join James Beck, PhD, Parkinson's Foundation Chief Scientific Officer, and Roy Alcalay, MD, MS, Principal Investigator of PD GENEration, as they share the latest updates on the study’s progress and unveil key findings that may be able to shape the future of Parkinson’s disease (PD) treatment and care.
PD GENEration is global research study that provides genetic testing and genetic counseling at no cost for people diagnosed with Parkinson’s. Learn more.
Resisting Parkinson’s Disease through Restoring Mitochondria Recycling
The ability of a cell to recycle its defective parts is crucial for it to remain healthy and functional. This is especially true for neurons, which have some of the most complex processes to manage in the body and little room for inefficiency. In certain forms of Parkinson’s disease (PD), proteins involved in those critical recycling processes are damaged, which is believed to cause affected neurons to break down over time.
Daniel Finley, PhD, a recipient of a Parkinson’s Foundation Impact Award, believes that he and his co-investigator Elena Ziviani, PhD, have found a “backup” compound that could fill in and restore neurons’ recycling abilities. With sufficient research and experimentation, this compound could become a new treatment that slows or prevents PD progression.
Cells require a consistent and efficient supply of energy to function properly. This is provided by mitochondria, cellular powerhouses that turn oxygen into renewable chemical energy. Over time, these powerhouses wear down and eventually need to be recycled so that new mitochondria can be made.
A protein called Parkin plays a major role in defective mitochondria recycling, and PD-linked mutations have been discovered that cause Parkin to become nonfunctional (in fact, the name “Parkin” comes from its discovery through PD research). Without functional Parkin, defective mitochondria clog up neurons and lead to their degeneration.
In summary, healthy neurons rely on their ability to recycle defective parts, but in Parkinson’s, mutations in the Parkin protein hinder this process, leading to degeneration. Drs. Finley and Ziviani have identified a potential alternative way to stimulate the recycling function, which can potentially lead to new treatments.
Recent experiments conducted by Dr. Ziviani have revealed that a compound they discovered, called IU1, can enhance an alternative mitochondria recycling process in neurons with dysfunctional Parkin. Additional chemistry led to the discovery of an IU1 variant, called IU1-366, that works even better. Next, the lab will test how it works in mice to ensure its safety and effectiveness for future human trials.
From his lab at Harvard Medical School in Boston, MA, Dr. Finley will first administer IU1-366 to mice and measure how that changes mitochondria upkeep in brain neurons.
Then, he will use mice genetically modified to have dysfunctional Parkin, simulating PD, to see if IU1-366 can overcome the disease-related mitochondria recycling issues. Across all mouse experiments, Dr. Finley will also monitor how IU1-366 affects the animals’ general health, assessing whether the treatment has side effects.
Finally, Dr. Ziviani will delve deeper into the biochemistry of IU1-366 using neurons in petri dishes, looking to better understand the mechanisms behind how the compound works to guide future therapeutic improvements.
These studies will determine if IU1-366 could be a future treatment for people with Parkin-affected PD, opening a potential new option that may slow disease progression.
Speaking on the merit of his upcoming research, Dr. Finley said, “With this award, we will be able to assess more deeply, using a mouse model, whether IU1-366, or a closely related compound, could have therapeutic benefit in humans. We are very excited to move this work forward and are hopeful for interesting results.”
Exploring DNA “Safety Caps” as a Potential Source of Neuron Loss in Parkinson’s
The biological hallmark of Parkinson’s disease (PD) is a progressive loss of neurons in the brain, particularly ones that produce the neurotransmitter dopamine. What makes these neurons uniquely vulnerable to malfunction has been a major subject of research, as understanding their weaknesses could lead to new treatments that protect them from failing.
Oxidative damage (where chemically reactive forms of oxygen molecules cause disruptions in cells) has been linked to PD-associated dopamine neuron loss. However, we still don’t know exactly how reactive oxygen molecules lead to the death of neurons.
Edward Burton, MD, PhD, and recipient of a Parkinson’s Foundation Impact Award, believes the answer may lie with telomeres, the protective “caps” on chromosomes linked to aging. This is one of the most detailed studies to date on the role of telomere damage in PD.
What is a telomere?
Telomeres are the long stretches of repeating DNA patterns found at the ends of chromosomes. They act as a "safety cap," protecting chromosome ends from deteriorating or being inappropriately recognized as areas of DNA damage. This is one of the first studies to link telomeres to Parkinson's disease.
Cells need a way to keep the delicate ends of their DNA protected from deteriorating or being incorrectly recognized as areas of DNA damage. The solution to that problem is telomeres, the long stretches of repeating DNA patterns found at the ends of chromosomes. These patterns protect chromosome ends, but get progressively shorter every time a cell divides, limiting the lifespan of cells that routinely divide, such as skin, blood and intestinal cells, and contributing to aging.
The importance of telomeres in neurons has not been well investigated, mainly because neurons do not divide once established and therefore their health and lifespan should not be limited by telomere shortening.
Dr. Burton and collaborators from their labs at the University of Pittsburgh in Pennsylvania, have recently discovered that another mechanism may link faulty telomeres to PD. While neurons may not show telomere shortening as a result of cell division, damage to their telomeres — particularly oxidative damage already linked to PD — could still trigger emergency DNA damage responses that impair neuronal function and eventually cause cell death.
“This is an exciting new research area in response to several recent discoveries about telomere biology and its role in the aging brain” - Dr. Burton
To test his hypothesis, Dr. Burton will first take postmortem brain tissue samples from people who had PD and investigate if their dopamine neurons had signs of oxidatively-damaged telomeres. This will tell him if he’s on the right track with his theory that damaged telomeres are associated with PD.
For the next part of his research, Dr. Burton will use genetically modified zebrafish, in which he can trigger oxidative damage in neurons on demand using a technique called chemoptogenetics. By specifically causing oxidative damage in dopamine neurons, he will be able to see if the neurons’ telomeres are impacted and lead to a DNA damage response that could harm the cells.
Ultimately, Dr. Burton will generate a special genetically modified zebrafish model that allows him to damage the neuron telomeres directly and specifically, further investigating if telomere damage could be the reason that dopamine neurons die in PD.
How does studying fish help further Parkinson’s research?
Zebrafish share more than 70% of the same DNA as humans. They are a widely used animal model for neuroscience research. They are useful and effective for experiments for many reasons:
Their brain and nervous systems are functionally similar to humans, including the utilization of dopamine neurons.
They have telomeres similar to humans.
Genetic modifications can create zebrafish with transparent skin, allowing their brains to be studied directly under a microscope in an intact living animal.
By exploring this innovative telomere-linked mechanism behind neuron loss in PD, Dr. Burton hopes to set the foundation for future therapies and treatments that bolster telomeres to help protect dopamine neurons and prevent disease progression.
Speaking on his upcoming research, Dr. Burton said “This award provides a unique opportunity to develop a new collaborative program that we hope will help understand why brains cells malfunction and die in PD. As a clinician caring for patients with PD, this is an important goal, as it may eventually help us develop treatments that slow disease progression.”
Creating Virtual Brains to Study how Parkinson’s Disease and Depression Interact
One of the most common non-movement symptoms experienced by people with Parkinson’s disease (PD) is depression. While the mental health impacts of PD-associated depression are debilitating on their own, they have also been associated with increased PD severity. This implies that the neurological changes in the brain that cause depression may also affect the progression of PD. Therefore, better understanding this overlap could improve treatment strategies for people with both.
Henricus Ruhe, MD, PhD, and recipient of a Parkinson’s Foundation Impact Award, will be using sophisticated brain mapping technology to investigate this subject, seeking new ways to personalize treatments for those with depression and PD.
For this research, he will collaborate closely with Morten L. Kringelbach, PhD, from Oxford University and Gustavo Deco, PhD, from Pompeu Fabra University in Barcelona, who developed the techniques.
Dr. Ruhe, from his lab at the Radboud University Medical Center in Nijmegen, Netherlands, a Parkinson’s Foundation Center of Excellence, plans to utilize a new neuroscience research tool called whole-brain computational modeling. The science and math involved with this tool is complex, but put simply, this technique allows researchers to take data from a person’s MRI scans and create a digital model of their brain.
Within each of these models are nodes, small brain areas whose neurons seem to generally activate together. Based on blood flow measured with MRI-data, the interaction patterns between nodes are mapped and measured to track how signaling information flows through the brain. Additional data, such as physical anatomical distances in the brain, will also be used to bolster the models.
Using previously collected clinical MRI data from people with PD, some with and some without depression, Dr. Ruhe will be able to generate brain models for his testing. By analyzing and comparing them, he hopes to identify how information flow in the brain is altered by depression in PD contexts.
In addition, in another cohort of PD-patients without and with depression, where MRI scans taken without (OFF) and with (ON) the use of levodopa medication will provide valuable information about how PD treatment affects depressed and non-depressed brains differently.
These established brain models can then be used to conduct in silico experiments — meaning that instead of working with cells in petri dishes (in vitro) or with live animals (in vivo), the testing is done with computer simulations.
In these simulations, Dr. Ruhe will aim to modify specific nodes and see how the rest of the brain reacts and reorganizes in response. These disruptions can be designed to mimic medications, estimating how they would work in the brains of people with and without PD-linked depression.
Performing these perturbations across the different PD brain models and comparing the outcomes will provide:
Major insights into which regions are most critical to brain function in PD and depression.
What therapies potentially work best for people with PD and depression, improving the scope and effectiveness of personalized treatments in the future.
Speaking on the importance of this award for his research goals, Dr. Ruhe said, “I am honored to have received this prestigious award. This will help our team and the Parkinson’s community to develop whole-brain models to better understand and preferably modify non-motor symptoms in PD. This will have substantial impact on selections of treatment of depression in PD patients by identifying susceptible brain regions for different forms of treatment.”
