My PD Story

Silas Buck
Researchers

Silas Buck, PhD

2024 Postdoctoral Fellowship 

Uncovering a Missing Link Between Genetic Mutation and Protein Clumping in PD 

Several genetic mutations linked to the development of Parkinson’s disease (PD) have been discovered over decades of research. However, fully understanding how those mutations can cause PD is an ongoing scientific challenge.  

One such PD-associated mutation leads to the production of a malfunctioning version of the protein LRRK2. Faulty LRRK2 is believed to disrupt several important processes within neurons and consequently contribute to PD progression, but how exactly these disruptions lead to the disease is still being studied.  

Silas Buck, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship, believes a relatively understudied protein may be affected by mutant LRRK2 and drive PD-related cellular breakdown. Through his experiments, he will seek to understand how this protein (called HDAC6) is corrupted in LRRK2-associated PD and how we might use this knowledge to create new treatments that prevent disruption to slow the disease. 

When looking at the posthumous brain tissue of people who had LRRK2-mutant PD, scientists have routinely seen unhealthy aggregates or clumps of a protein called tau. Similar to alpha-synuclein clumping, tau clumping is believed to contribute to the disease-related breakdown of dopamine neurons and is associated with PD dementia. HDAC6 is a protein with many responsibilities, one of which is to regulate tau and keep it from clumping. However, Dr. Buck hypothesizes HDAC6 may be a missing link connecting LRRK2 to tau clumping in PD. 

“Determining the potential positive effect of HDAC6 inhibition in Parkinson’s disease could have an immediate impact on people with Parkinson’s disease,” said Dr. Buck. 

Dr. Buck, working in the lab of Dr. Laurie Sanders at the Duke University School of Medicine in Durham, NC, a Parkinson’s Foundation Center of Excellence, will be conducting research to see if and how mutant LRRK2 causes disruptions in HDAC6 that lead to PD-associated tau clumping. Using neurons grown in petri dishes, Dr. Buck will first measure how much LRRK2 and HDAC6 interact in healthy brain cells.  

Then, he will introduce mutant LRRK2 into those cells and analyze how that affects the LRRK2-HDAC6 interactions and if such changes result in tau clumping. Finally, Dr. Buck will investigate if mutant LRRK2’s impact on HDAC6 also contributes to disrupted mitochondria repair and cleanup, another cellular stressor commonly seen in PD brain tissue.  

Uncovering more biochemical links in the chain between gene mutation and PD means more opportunities to intervene in the disease’s progression. Through Dr. Buck’s experiments, we will understand more about HDAC6’s role in PD development and how it could be the target of new future therapies, expanding the effective medication options and improving doctors’ ability to provide genetically personalized treatment plans for people with Parkinson’s. 

When asked about the personal and scientific impact of this Parkinson’s Foundation support, Dr. Buck said “Receiving this postdoctoral fellowship allows me to pursue my passion of performing exciting and important research that could one day help substantially improve the lives of people with Parkinson’s disease. It has always been my dream to make a difference in the health of others through research, and I hope to achieve that through this project.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers

My PD Story

Inés Patop
Researchers

Inés Patop, PhD

2024 Postdoctoral Fellowship 

Investigating How Parkinson’s Derails Crucial Transport Routes Within Neurons 

Neurons, the cell type that transmits information in our brain and nervous system, are complex in ways that have puzzled researchers for decades. Depending on their location and role in the body, neurons can vary wildly in shape and activity, with some stretching up to a meter in length to perform their signaling duties. Their unique form and function also create challenges for neurons, having to manage cellular upkeep across long distances to stay fit and functional.  

The dopamine-producing neurons in the brain progressively lost in Parkinson’s disease (PD) are no exception. How the disease may impact the cells’ critical maintenance is still not well understood. Inés Patop, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship, will be utilizing new and sophisticated biological tools to improve our understanding of not just how PD may affect neuronal upkeep, but specifically where it is most damaging within the cell and how we can use that knowledge to design more efficient therapies. 

While their shape and size vary across the body, all neurons are composed of two distinct parts:  

  1. The soma: the larger main area of the cell that contains the DNA-storing nucleus 

  1. The neurites: the tendril-like extensions that reach out to other cells to either receive signals (as dendrites) or convey signals (as axons).  

In each of these parts are mitochondria, miniature cell powerplants that require routine maintenance to keep the cell working properly. Parkinson’s disease has been associated with mitochondria misfunction for more than 30 years, being most of the PD-associated mutations involved in the process of clearing defective mitochondria.  

The trick is that the blueprints needed for proper mitochondrial function and to repair and clear defective mitochondria come from the nucleus in the soma, so to maintain or clear the far-away mitochondria in the neurites, the neuron needs to print and transport those blueprints (called RNA) across the cell. That process requires significant coordination to execute properly, coordination that is likely disrupted in neurons affected by PD-associated mutations.  

From the lab of Dr. Stirling Churchman at Harvard University in Boston, MA, Dr. Patop will utilize special growing chambers that will allow them to isolate and study the soma and neurites of neurons individually. They will then run complex biochemical analyses to see how RNA printing and transport, mitochondria repair and more differ between the distinct cell regions, and how each is affected by PD mutations. From this data, Dr. Patop hopes to better understand how PD may affect neurons differently from soma to dendrites, potentially leading to new future treatments that target the most impacted regions of the cells. 

When asked what the Parkinson’s Foundation research funding means to them, they said, “I am confident this opportunity will lay a strong foundation for my future career, empowering me to make meaningful contributions to the scientific community and, ultimately, improve the lives of those affected by Parkinson's disease. Through this research, we expect to identify new regulatory mechanisms implicated in PD, potentially identifying novel drug targets for treatment. The impact of this research could significantly advance our understanding of PD and pave the way for innovative therapeutic strategies.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers

Advancing Research

Meet the Researcher Shining a Light on Parkinson’s Treatment-Induced Impulsivity

Xiaowen Zhuang, PhD

Dopamine replacement therapies, such as dopamine agonists and the commonly used drug levodopa, can alleviate some of the more debilitating movement symptoms of Parkinson’s disease (PD), restoring precious autonomy and quality of life to those that need it. However, these therapies are not without side effects, one of which is the potential to develop an impulse control disorder

Up to 40% of people who take dopamine-replacing drugs for their PD experience impulse control disorders (ICDs). ICDs can present themselves in many ways, including gambling addictions or excessive eating.  

Xiaowen Zhuang, PhD, a recipient of a Parkinson’s Foundation Launch Award, wants to better understand the neuroscience behind this medication-induced impulsivity so that we can improve future treatments to avoid this side effect altogether. 

Dr. Zhuang will study ICD using mice, measuring what is known as delay discounting behavior, which is how much a subject is willing to ignore an immediate smaller award (like treats) and wait for a larger award instead. She uses tools called operant boxes that allow her to train mice on this “small award now vs. larger reward later” scenario and collect data on how their impulsivity changes in different conditions. 

Delay Discounting Behavior

The degree to which a delay for greater reward discounts the value of that award compared to a smaller, immediate one in the mind of the decision-maker. 

  • Low impulsivity = Low delay discounting > Willing to wait for larger reward  
  • High impulsivity/ICD = High delay discounting > More likely to take immediate, smaller reward 

Once the mice are trained, Dr. Zhuang will then utilize a cutting-edge scientific method called optogenetics to turn on or off certain decision-associated neurons in the brain and observe how that affects the mice’s impulsivity. From these experiments, she hopes to home in on the specific parts of the brain connected to ICD and discover how exactly they are affected by PD medications. This knowledge could then guide the development of future treatments where such impulsivity symptoms are no longer a concern. 

Dr. Zhuang’s interest in this topic began once she joined the lab of Alexandra Nelson, MD, PhD, at the University of California, San Francisco, CA, in 2020. 

“Discussions with my mentor, Dr. Nelson, deepened my understanding of the severe complications experienced by Parkinson's disease patients, among which impulse control disorder is a salient one,” Dr. Zhuang said. “These severe consequences intensified my desire to learn new skill sets to dissect the circuit mechanisms.” 

Shortly after joining, the COVID-19 pandemic forced all researchers away from labs and into their homes. But this didn’t stop Dr. Zhuang’s scientific enthusiasm.  

“While she had little coding experience or familiarity with operant behavior prior to joining my lab, with only modest guidance and the loan of a power drill and soldering iron, she built custom operant boxes at home, wrote code to run them, and developed a plan for progressive training and testing with a delay discounting task,” said Dr. Nelson. “She tested her boxes over Zoom, using a fuzzy mouse toy to trigger nose pokes.” 

Back in the lab and ready to begin her Foundation-supported research, Dr. Zhuang is excited about how her research may improve the lives of those relying on PD medicine.  

“Despite its prevalence, our understanding of ICD’s cause is limited, and effective treatments or interventions are yet to be discovered,” she said. “My research could pave the way for new treatments for Parkinson's disease that help manage symptoms more effectively without leading to these impulse control issues.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers

Science News

New Study Further Personalizes Deep Brain Stimulation

Science News Blog header

Deep brain stimulation (DBS) is a surgical treatment that provides relief to people with Parkinson's disease (PD) who experience movement symptoms and medication side effects. Since its U.S. Food and Drug Administration (FDA) approval to treat PD symptoms in 2002, DBS can help reduce medication needs and stabilize symptoms. PD symptom severity often varies throughout the day — because DBS provides constant electrical stimulation, there can be times when it is too much or too little, which limits its effectiveness. 

A recent study has developed a new approach, known as adaptive DBS, which has the potential to further personalize DBS treatment for Parkinson's. It was recently tested in a small clinical trial reported in Nature Medicine

Utilizing custom computer algorithms and artificial intelligence (AI), adaptive DBS can detect symptom changes in real time by monitoring brain activity that is specific to each participant. When it detects changes, the system delivers precisely calibrated electrical pulses to counteract these shifts. 

The system delivers more electrical stimulation during periods of stiffness (bradykinesia) and less during phases of involuntary movement (dyskinesia). It also adjusts stimulation based on the effectiveness of levodopa medication, providing more stimulation when the medication wears off and less when it's active.  

About the Study & Results

deep brain stimulation

The clinical trial enrolled four participants who were diagnosed with Parkinson’s at least six years earlier. Each participant underwent conventional DBS surgery. Researchers collected brain activity data for each participant, then used that data to create personalized algorithms to detect and respond to symptom fluctuations. Months after the initial DBS surgery, each participant was switched to adaptive DBS. 

To compare the two types of DBS, participants switched between conventional stimulation and the personalized version every two to seven days over a period of two months (one month spent with each stimulation type). Neither the participants nor most of the researchers knew which type of stimulation was being delivered at any time. Participants reported their symptoms daily, and wearable monitors detected changes in their movement symptoms. 

All four participants experienced nearly a 50% reduction in time spent with their most troublesome symptom when adaptive DBS was active compared to conventional stimulation. They reported that their worst symptoms went from persisting for about 25% of their day down to about 12%. Additionally, adaptive DBS did not worsen other PD-related symptoms. Overall, participants reported an improved quality of life with adaptive DBS.  

By dynamically adjusting stimulation parameters based on real-time brain signals, adaptive DBS appears to offer a more personalized and effective treatment for Parkinson's than conventional DBS. 

Highlights 

  • 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. 

  • All four participants experienced a nearly 50% reduction in time spent with their most troublesome symptom when adaptive DBS was active. 

  • Adaptive DBS did not worsen other PD-related symptoms. 

  • Participants reported improved quality of life with adaptive DBS compared to conventional DBS. 

What does this mean? 

Adaptive DBS may be an evolved version of DBS treatment for improving movement symptoms of Parkinson’s. The study finds that using new technology can further personalize DBS currents and make DBS even more effective in treating troublesome PD symptoms. However, developing the customized algorithms for each participant was time consuming in this small study, and it will take time before it becomes widely available. 

What do these findings mean to the people with PD right now? 

It’s important to keep in mind that this was a small study of only four participants. The study, and its technology will need to be replicated on a much larger scale. Still, the study findings are exciting and bring hope for the PD community, as proven by its media coverage. The concept of adaptive DBS may eventually become the standard for DBS treatment, and with further development and refinement, people with conventional DBS may be able to use adaptive DBS in the future.  

Adaptive DBS is still in testing and it does not have widespread availability. People should talk to their doctors about their treatment options and if they have DBS, ask doctors or their care team to inform them if a similar adaptive DBS study begins to recruit.  

Get Involved with Parkinson's Research

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Advancing Research

Parkinson’s Foundation Presents Five Findings at International Congress of Parkinson’s Disease and Movement Disorders®

Researcher in lab

Every year thousands of Parkinson’s disease (PD) experts and researchers share research findings that have the potential to help people living with Parkinson’s at the International Congress of Parkinson’s Disease and Movement Disorders. This year the conference took place from September 27 to October 1 in Philadelphia, PA.  

The Parkinson’s Foundations shared five new Parkinson’s studies, revealing new information about genetics research, care and our work with the Black and African American community. These findings offer new hope for people living with PD and caregivers alike.  

Explore the five research findings the Parkinson’s Foundation shared with the international PD community below:   

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1. Expanding the PD Generation Study to Increase Clinical Genetic Testing and Counseling Using Whole Genome Sequencing Among Diverse Parkinson’s Populations 

PD GENEration: Mapping the Future of Parkinson’s disease is a Parkinson’s Foundation research study that offers genetic testing and counseling, in English and Spanish, to people with Parkinson’s through a whole genome sequencing platform. This study aims to simplify access to clinical genetic testing to people with PD and offer educational materials to clinicians on PD genetics. 

Key Takeaways: 

  • The study has enrolled 18,003 participants, as of September 2024. 

  • The study has expanded to five countries from Latin America (Colombia, Chile, Peru, Mexico, Ecuador), Israel, Canada, and 10 additional sites in the U.S. that focus on underrepresented populations. 

  • 12.2% of people with Parkinson’s, who have completed testing, tested positive on the PD GENEration 7-gene panel. 

  • By providing genetic testing to all those interested and 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

PD GENEration goals include helping accelerate clinical trials in PD, improving PD care and research and empowering people with PD and their care teams. 

Learn more & enroll in PD GENEration.

2. Engagement of the Black and African American Community in PD Genetics Research 

Advancements in understanding the biological pathways of Parkinson’s have largely been focused on people of European ancestry. There is a critical need to understand genetic differences across populations, including people with African ancestry. The Parkinson’s Foundation partnered with Morehouse School of Medicine, a historically Black institution of medicine to improve inclusion in PD GENEration, prioritize PD awareness, education and resources; and tailor our research advocacy training program — the Learning Institute.   

Key Takeaways: 

  • Through this partnership with Morehouse School of Medicine, from November 2021 to March 2024, 157 Black and African American participants enrolled in PD GENEration.  

  • 14 community education events were held, including the Learning Institute in September 2023. 

  • Media was developed and utilized to expand reach and included two webinars, five podcasts and six blogs/news articles.  

Establishing partnerships with trusted sources of the Black community is critical to providing equitable access to PD education and resources, including PD GENEration. Focusing on diversity and inclusion in PD GENEration will accelerate breakthroughs towards a cure for PD.     

Learn more about our impactful partnership with Morehouse. 

3. Benefits of Parkinson’s Team Training Are Maintained Long-term 

The goal of Parkinson’s Foundation Team Training is to provide more coordinated and complete patient-centered care to improve the quality of life of people with PD and caregivers. Our study aimed to demonstrate the effectiveness of the training program and determine if the benefits of Team Training are maintained long-term. 

Key Takeaways: 

  • Through Team Training, team members become more effective in delivering better interprofessional, patient-centered care.  

  • Results showed significant and sustained improvements in: 

  • Healthcare professional confidence in various measures of providing care 

  • Team coordination working with persons with PD and their care partners 

  • Understanding of the other team member roles and how team members can assist in the care of persons with PD and their care partners. 

  • The effectiveness of the Team Training program’s education is maintained and sustained long term. Better care leads to better lives for those living with PD and their care partners. 

Parkinson’s Foundation Team Training provides a continuing education program for healthcare professionals to learn more about PD and how to develop and maintain an effective PD interprofessional team.  

Explore our Learning Lab courses, designed for healthcare professionals.  

4. Engage, Educate and Empower: Parkinson’s Research Advocates from the Black and African American Community  

Black and African American people with Parkinson's face significant disparities in care, including delays in diagnosis and treatment, limited access to care and historical exclusion from research. To address these challenges, the Parkinson’s Foundation Research Advocacy Training program, the Learning Institute, was tailored to engage, educate, and empower the Black community in Parkinson’s research. 

Key Takeaways: 

  • The Learning Institute was held in September 2023. 33 people from the Black community were trained in research advocacy.  

  • Many research advocates felt prepared to begin research advocacy (79%) and most felt excited about the work they can do as a research advocate (83%). 

  • To date, 17 advocacy tasks were completed by 26 research advocates, including presentations at local churches and health fairs, panelists at a Parkinson’s Foundation community-based program, and partnerships with researchers.  

The Learning Institute empowered African Americans living with PD to become advocates for community outreach and engagement. This program has the potential to drive meaningful change, enhance health equity, and improve outcomes for those living with PD in the Black and African American community. 

Learn more about our research advocates. 

5. Hospital Care Learning Collaborative: Sharing Strategies to address the Parkinson’s Foundation Inpatient Clinical Care Standards 

With the launch of the Parkinson’s Foundation Hospital Care Learning Collaborative, the Foundation in partnership with healthcare leaders, clinicians and institutions, aims to eliminate preventable harm and promote higher reliability in care for people with Parkinson’s in the hospital. The Learning Collaborative work to implement quality improvement projects focused on improving hospital safety for people with PD. Participants shared strategies and best practices to address the hospital care standards, as outlined in the Parkinson’s Foundation Hospital Care Recommendations.  

Key Takeaways: 

  • A framework to work with the hospital IT team to request adjustments to the Electronic Health Record, including the ability to customize times for Parkinson’s medication orders. 

  • Strategies to avoid medication delays in the event of safety concerns due to swallowing challenges (dysphagia), including the use of crushed Parkinson’s medication and an automated trigger for a Speech Language Pathologist evaluation.  

  • The use of an Electronic Health Record alert when unsafe medications are ordered, offering alternatives that are already approved by the hospital Pharmaceutical & Therapeutics committee. 

The Parkinson’s Foundation is committed to improving hospital safety for people with PD. In addition to our Hospital Safety Guide, a resource for people with Parkinson's and care partners, the Foundation works with hospitals and health systems to help promote awareness and delivery of the best care for the Parkinson’s community.  

Read and download the Hospital Safety Guide today. 

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Stay up to date with Parkinson’s Foundation through our Parkinson’s Today blog.  

My PD Story

Trisha Pasricha headshot
Researchers

Trisha Pasricha, MD

2024 Impact Award 

Exploring Gut Health Biomarkers as Early Indicators for Parkinson’s  

The ability to identify Parkinson’s disease (PD) in people before the onset of progressing movement and cognitive changes is a major goal of PD research. Through retrospective studies, some early symptoms have been routinely noted in people years prior to their PD diagnoses, making them potential flags for catching the disease sooner. Gastroparesis, which consists of bloating and nausea, is an example of a symptom experienced earlier in life by a large majority of those with PD. However, this condition is also common amongst people who never develop PD, making it difficult to use as a reliable PD indicator without more data.  

Trisha Pasricha, MD, and recipient of a Parkinson’s Foundation Impact Award, aims to compare the gut biology of those with and without PD using innovative new technology, to discover the biomarkers of PD-linked gastroparesis that will improve future diagnoses. 

Previous research into the active biology of the gut has been limited due to the difficulty in collecting useful tissue samples from live donors. Fortunately, recent technological advances in biopsy collection tools now allow researchers like Dr. Pasricha to safely obtain “full-thickness” gut tissue samples with more deeper layers of the gut wall for study.  

From her lab at the Beth Israel Deaconess Medical Center in Boston, MA, a Parkinson’s Foundation Center of Excellence, Dr. Pasricha will analyze the gastric biology of full-thickness gut tissue samples collected from: 

  • People with PD in all stages 

  • People with gastroparesis, without PD  

  • People without either condition  

Each layer of the gut wall consists of a diverse mix of muscle, connective tissue, neurons and immune cells. Dr. Pasricha, using a wide range of measurement tools and techniques, will investigate which cell types in which layers are most differentially impacted in PD gastroparesis compared to non-PD gastroparesis. The goal of these comparisons is to highlight potential gut biomarkers that will allow future physicians to spot PD earlier from initial gastrointestinal issues.  

She will also compare these biomarker results to clinical assessments from the tissue donors with PD, looking for correlations between gut health and disease severity to further explore the link between the two. 

As a clinician working directly with people with PD experiencing gastrointestinal issues, Dr. Pasricha is inspired to receive the Parkinson’s Foundation grant and motivated to begin this translational research.  

“I have met countless patients living with Parkinson's who seek my help treating their gastrointestinal symptoms,” she said. “I am grateful that because of this award I will be able share with my patients that I am part of the community of scientists working to address the bigger unmet needs of patients like themselves. These findings may be leveraged toward establishing future gastrointestinal biomarkers or therapeutic targets to help alleviate those suffering from this disease.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers

My PD Story

MTR Headshot Henry Houlden
Researchers

Henry Houlden, PhD

2024 Impact Award 

Exploring a Unique Genetic Risk Factor for Parkinson’s in Black and African American Populations 

Along with aging and environmental factors, genetics is one of the three major factors involved in the development and progression of Parkinson’s disease (PD). Ongoing research aims to find disease-associated gene mutations to better understand PD and how to prevent or treat it. While many critical discoveries have been made from such studies, it is important to note that the research to date has been predominantly conducted using genetic samples from those of European ancestries, leaving a gap of scientific knowledge for those people with PD of other ancestries.  

Henry Houlden, PhD, a recipient of a Parkinson’s Foundation Impact Award, will be expanding the diversity of our genetic understanding of PD by studying a newly discovered disease-associated mutation found nearly exclusively in African American and African-admixed (people of African heritage outside of Africa) populations through a fruitful partnership with Professor Njideka Ulunma Okubadejo, MBCHB, MD, FMCP, FAAN, and her team in Lagos, Nigeria, and colleagues at the National Institutes of Health in Bethesda, MD. 

The mutation in question was found when Dr. Houlden and colleagues previously performed a genome-wide association study with DNA samples from nearly 200,000 people of African American and African-admixed ancestry, approximately 1,500 of whom have PD. This type of study analyzes the entirety of each person’s DNA and highlights similarities and differences between the genes of those with and without the disease, offering potential genetic clues as to which mutations are linked to PD.  

One of the clues Dr. Houlden found was a PD-linked mutation in the DNA region that helps make an enzyme called GCase (glucocerebrosidase). While PD-linked mutations in this region have previously been found, this mutation seems to affect how the enzyme works in ways that have not been observed before in similar, European ancestry-related mutations. 

To better understand how this mutation may lead to PD, Dr. Houlden will measure various genetic and biochemical factors related to GCase in 72 blood and tissue samples from people of African American and African-admixed ancestry with and without PD. He will also use parts of those samples to create petri-dish neurons of these donors, allowing him (and future researchers) to more effectively investigate how the mutation may drive the development of PD.  

From these experiments, Dr. Houlden will generate valuable data advancing our understanding of this African-ancestry PD risk factor and contribute to new PD treatments for these underrepresented populations. 

From his lab in the University College London Institute of Neurology in the United Kingdom, Dr. Houlden is ready to continue his impactful research through Parkinson’s Foundation grant funding.  

“I am very interested in Parkinson's disease in diverse populations I think this is a major link that is missing in our research strategy and will bring significant findings important to PD across the world,” he said. “The award will also exemplify how foundations around the world, such as the Parkinson's Foundation, are funding global research and understand the need to investigate and form partnerships with diverse populations for research.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers

My PD Story

Fuu-Jiun Hwang headshot
Researchers

Fuu-Jiun Hwang, PhD

2024 Postdoctoral Fellowship 

Exploring and Unlocking Motor Memory in Parkinson’s 

Despite how simple daily movements like walking, using utensils, or riding a bike may seem, they require the precise and instantaneous activation of complex networks of neurons. As we learn to perform these types of movements, the brain stores these neuronal activation patterns, allowing us to utilize them seamlessly in the future, making the movements feel effortless. For people with Parkinson’s disease (PD), that effortlessness diminishes as common PD symptoms make even simple movements challenging. 

Fuu-Jiun Hwang, PhD, recipient of a Parkinson’s Foundation Postdoctoral Fellowship, aims to discover whether those motor memories are still present in the brain but have become inaccessible in PD, and if so, how they can be reactivated. 

The scientific term for how the brain “memorizes” physical actions is motor learning. This process results in the formation of motor memory engrams, which are the specific activation patterns and timing of neurons needed to perform a memorized action. 

Motor memory engrams are like songs played by an orchestra. Specific musicians (neurons) must play the right notes in the right order (activation patterns) to perform the song. After enough practice, when the conductor asks the orchestra to play a certain song (a movement), they know exactly what to do (effortless engram utilization). 

Dr. Hwang, working in the lab of Jun Ding at Stanford University, will use advanced neurochemical tools in mouse brains to visualize and map the motor memory engrams associated with a forelimb-reaching task, a well-established motor learning behavior task in mice. He will then induce PD-like brain disruption in the mice and observe whether the same engrams activate when the mice perform the learned task, or if the disease alters the neuron patterns involved. Additionally, Dr. Hwang will explore whether administering levodopa — the most potent PD medication — can restore the original engrams altered by the disease. 

Previous neuroscience research has shown that repeated practice and performance of actions rewires the brain to reinforce and improve the associated motor memory engram, a phenomenon known as synaptic plasticity. Dr. Hwang plans to take his experimental model further to examine whether synaptic plasticity associated with the motor engram is also impacted by PD. 

The discoveries from these experiments will help Dr. Hwang and other PD neuroscientists better understand how motor memory and learning are affected by Parkinson’s disease, and what potential treatments could be developed to address movement symptoms at their source. 

Reflecting on the significance of the Parkinson’s Foundation grant, Dr. Hwang said, “Receiving this award is crucial for supporting my research on motor engrams and their application to Parkinson’s disease. Ultimately, this award will help me contribute to the understanding of PD and develop novel therapeutic strategies, potentially improving the lives of individuals affected by this debilitating disease.” 

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers

My PD Story

Rebecca Wallings headshot
Researchers

Rebecca Wallings, PhD

2024 Launch Award  

Giving Brain Immune Cells a Boost as a New Preventative Parkinson’s Therapy 

Immune cells play a critical role in protecting our bodies from infection and disease. As we slow down with age, these cells also become less effective. Aging is the greatest risk factor for Parkinson’s disease (PD), so learning how immune cells are affected by aging and how PD-related mutations may accelerate such impacts is of keen interest to researchers.  

Rebecca Wallings, PhD, a recipient of a Parkinson’s Foundation Launch Award, is investigating how aging impairs a certain type of immune cell outside the brain — and how this impairment impacts cells within the brain that contribute to the development of PD.  

Immune cells can be divided into two groups:  

  1. Innate immune cells that are the first responders to injuries and exposures. 

  1. Adaptive immune cells that “learn” from past infections to provide enhanced protection from repeat threats in the future.  

These two types of cells communicate and collaborate in complex ways to help the body recover quickly and stay healthy.  

Dr. Wallings, working in the lab of Dr. Malu Tansey at the University of Florida, has previously found that a PD-related mutation causes innate immune cells outside the brain in to become “exhausted,” unable to respond to infections or other inflammatory alarms in the body. Since these immune cells are so involved with other cell types to keep the brain healthy, this aging-related exhaustion likely has hidden causes and consequences worth exploring. 

In her upcoming experiments, Dr. Wallings will use human cell samples from donors with and without PD to see if innate immune cell exhaustion prevents them from being able to communicate with healthy adaptive immune cells. She will then utilize mice with and without PD-related mutations to better understand how this immune cell exhaustion plays into the progressive neurodegeneration common to PD, measuring and comparing brain health over time. 

“What the Parkinson’s Foundation has done with this award is show me that they are willing to invest in me, and they believe in the potential impact my research may have on the field and, most importantly, on patients’ lives.” 

There is evidence that immune cell exhaustion is due to malfunctioning mitochondria, the powerhouses of the cells that provide the energy they need to perform their functions. Delving into this further, Dr. Wallings will also test if reinforcing or repairing these immune cell mitochondria could have potential to serve as a future preventative treatment option for PD. 

Asked about the impact of her research and how this award supports it, Dr. Wallings said, “My research is at the forefront of a potential paradigm shift in the neurodegeneration field and may change the way researchers think about the role of the immune system in PD.”  

Meet more Parkinson’s researchers! Explore our My PD Stories featuring PD researchers

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Amitabh Bhattacharya
Researchers

Amitabh Bhattacharya, PhD

2024 Postdoctoral Fellowship 

Using Ultrasound Stimulation as a New Way to Address Freezing of Gait 

Freezing of gait is a common Parkinson’s disease (PD) symptom characterized by a temporary, involuntary inability to move. This symptom can be frustrating at best and dangerous at worst, as it increases the risk of falls. Unfortunately, standard dopaminergic medications and even deep brain stimulation (DBS) have shown little to no benefit in treating freezing of gait, highlighting the need for alternative therapies. 

Amitabh Bhattacharya, PhD, recipient of the Parkinson’s Foundation Postdoctoral Fellowship, believes that non-invasive ultrasound stimulation (TUS) could offer a promising solution for reducing freezing of gait symptoms without the need for expensive and invasive surgery. 

Working in the lab of Dr. Robert Chen, a 2023 Parkinson’s Foundation Impact Awardee, at the University Health Network (UHN) in Ontario, Canada, Dr. Bhattacharya will be leading a study to test the effectiveness of TUS in treating movement symptoms in people with PD who experience freezing of gait.  

Participants, recruited with help from the Toronto Western Hospital Movement Disorders Clinic, a Parkinson’s Foundation Center of Excellence, will first undergo a high-resolution brain scan to create a detailed map of their brain, focusing on the pedunculopontine nucleus (PPN), a key region that helps control movement. This initial scan will be used to model and plan the TUS treatment, ensuring that the sound waves are precisely targeted to hit the intended area of the brain. 

Over three visits in the following months, study participants will receive personalized TUS treatments to monitor if freezing of gait symptoms improve, measured with walking tests and clinical symptom severity scales. Follow-up MRIs will also allow Dr. Bhattacharya to observe how the treatment has influenced brain function over time, providing insights into the most effective stimulation protocols.  

The findings from this research will inform and shape future experiments and clinical trials, with the ultimate aim of developing ultrasound treatments for PD gait symptoms that are not only safe and effective but also widely accessible to those in need. Given the lack of effective treatments for freezing of gait, this research could pave the way for a much-needed breakthrough to manage this challenging symptom.  

When asked what the Parkinson’s Foundation grant means to him, Dr. Bhattacharya said, “This award is a major morale booster and a catalyst for innovation, allowing me to focus on developing treatments that can profoundly impact patient care. TUS treatment could revolutionize the management of freezing of gait, enhancing treatment outcomes for patients.” 

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