2021 Stanley Fahn Junior Faculty Award  

Targeting Brain Area Linked to Motor Problems Could Improve Movement

Taraz Lee, PhD, of the University of Michigan, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study the relationship between movement and cognitive systems in the brain known as the Attentional-Motor Interface (AMI).

In people with Parkinson’s disease (PD), there is now extensive evidence that several risk factors for ;falls might reflect deficits in the AMI. However, until now there has not been sufficient evidence from human research to show that AMI disruption leads to motor deficits in people with Parkinson’s.

“Our research has the potential to deepen our understanding of the progression of PD,” said Dr. Lee. “Perhaps, more importantly, our work also has the potential to open a new avenue for a therapeutic target that might improve day-to-day functioning in people with PD in the early stages of the disease.”

As Parkinson’s progresses, it can lead to cognitive impairments and gait disorders such as freezing and falls. Control of gait and balance requires extensive integration of cognitive, motor, and sensory functions. Growing evidence suggests that motor deficits in people with Parkinson’s are driven by changes in processing in the part of the brain called the frontal cortex that is associated with executive functions, such as the control of attention.

“One of the exciting new hypotheses of motor deficits in Parkinson's disease suggests that these deficits really begin to appear when attentional systems in the brain start to be affected by the disease,” said Dr. Lee. My lab has the tools and expertise necessary to really put this hypothesis to the test.”

Dr. Lee will use a non-invasive brain stimulation technique called transcranial magnetic stimulation (TMS) to find out if disrupting activity in the frontal cortex will worsen motor deficits in people with Parkinson’s, and whether enhancing activity in this same brain area may lead to improvements in motor function. Such a finding would provide a promising avenue for treatment.

Of his grant award, Dr. Lee said, “I am very excited by the opportunity to have our work provide positive impacts in the real world. I think it is incredibly important to understand the basic mechanisms of the brain to arm us with the knowledge necessary to fight diseases like PD and organizations like the Parkinson's Foundation really make a difference in helping to support researchers trying to do this work. My hope is that through this award we can generate enough research to garner federal funding that will sustain PD research in my lab for many years.”

2021 Stanley Fahn Junior Faculty Award  

How Brain Chemical Imbalances Lead to Movement Problems

Mark Howe, PhD, of Boston University, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study the role of a brain chemical called acetylcholine in Parkinson’s disease (PD) movement problems. The findings will offer new insight into potential diagnostic markers and novel treatment strategies for correcting brain chemical imbalances that can lead to movement disorders in Parkinson’s.

“I have long been fascinated by how our nervous systems select and invigorate actions,” said Dr. Howe. “In Parkinson’s disease (and other basal ganglia disorders), the process of translating intention into smooth, vigorous action is profoundly and persistently affected. What are the electrical and chemical signals in the brain that determine whether or not we act, and how do they become compromised in disease? This is a central unresolved question that inspires research in my laboratory.”

In people with Parkinson’s, the cells that make the brain chemical dopamine — called midbrain dopaminergic neurons — are impaired. As Parkinson’s progresses, more dopamine-producing brain cells die. The brain eventually reaches a point where it stops producing dopamine in any significant amount. This causes increasing problems with movement. Motor function depends on the coordinated interaction of dopamine and acetylcholine.

“We are only beginning to unravel the consequences of dopamine loss on the brain dynamics controlling action in the intact, behaving brain,” said Dr. Howe. “Studies have pointed to interactions between dopamine and the neurotransmitter, acetylcholine, as being particularly important for proper movement invigoration and control.”

Dr. Howe will use a combination of imaging approaches in mouse models of Parkinson’s to investigate the links between the depletion of dopamine, the interplay of dopamine and acetylcholine, and the progressive emergence of Parkinson’s-related movement deficits.

Ultimately, this knowledge will be invaluable for diagnosing Parkinson’s at the earliest stages and developing the most effective and side-effect free treatments possible.

The results of Dr. Howe’s work may also give people with Parkinson’s and clinicians a deeper understanding of why current treatments work or don’t work, helping to adjust surgical and pharmacological interventions to improve quality of life.

Of his Parkinson’s Foundation grant, Dr. Howe said, “Myself and other lab personnel have been eager to apply our basic knowledge and tools to Parkinson’s disease research, but we have lacked the financial support to do so. We are thrilled that this award will give us the means to pursue a natural extension of our ongoing research.”

2021 Postdoctoral Fellowship 

Protein Complex May Hold Key to Processes Leading to Brain Cell Degeneration

Hui Ye, PhD, of Baylor College of Medicine (a Parkinson’s Foundation Center of Excellence), received a Parkinson’s Foundation Postdoctoral Fellowship to study the role of a protein system called the retromer complex in the development of Parkinson’s disease (PD). Dr. Ye, along with a growing number of researchers, believes that a breakdown in this system provokes brain cell degeneration. Currently, the role of the retromer complex in brain nerve cells, and within the aging nervous system, is not well understood.

Retromer is responsible for recycling proteins. Mutations in one retromer protein called VPS35 contribute to late-onset Parkinson’s disease. The retromer also closely interacts with other proteins implicated in the risk of developing Parkinson’s.

“My career goal is to become an independent research scientist who combines basic sciences and technologies and collaborates with scientists and clinical physicians to translate biomedical research into beneficial treatments,” said Dr. Ye. “I anticipate that completing the studies proposed will shed light on key questions and form the basis of my future neurodegenerative disease research.”

Dr. Ye will use fly brains and human nerve cells to investigate the function of the retromer in communication between lysosomes (specialized cell vesicles that hold a variety of enzymes) and synapses (the point at which a nervous impulse passes from one neuron to another). She will determine whether this communication supports healthy brain aging.

Having a better understanding of the breakdown in this retromer-based communication system may lead to new targets for Parkinson’s treatment.

“Having witnessed the upsetting progression of symptoms in people with PD, including my grandfather, I understand how heartbreaking it is to fight against a disease with no known cure,” said Dr. Ye. “I have committed myself to scientific research for a better understanding of PD.”

Targeting Communication Among Nerve Cells to Improve Motor Symptoms in Parkinson’s

Beatriz Nielsen, PhD of the University of Colorado (a Parkinson’s Foundation Center of Excellence) received a Parkinson’s Foundation Postdoctoral Fellowship grant to study the balance between two neuromodulators — chemical substances that affect communication among nerve cells — and how it is altered in Parkinson’s disease (PD).

The findings may lead to new therapeutic strategies for PD.

A balance between the neuromodulators dopamine (DA) and acetylcholine (Ach), is essential for correctly executing goal-directed movements and habits. Goal-directed movements are conscious and planned motor functions oriented toward a specific goal. Habits are more automatic actions based on past success. An imbalance between the two neuromodulators is related to motor disorders such as Parkinson’s disease.

How ACh plays a role in this nerve cell communication is not well understood. Increased insight is needed to understand Parkinson’s motor dysfunction, and to develop new and more effective therapies. Dr. Nielson will study this question in two animal models of Parkinson’s.

“The first description of Parkinson’s disease was made two centuries ago but finding a cure or more effective therapies with fewer side effects that improve life quality remains a goal that has unfortunately not been reached,” said Dr. Nielsen. “I hope that understanding acetylcholine transmission and how it is altered following dopamine loss in this movement disorder opens doors for the development of new and more effective therapeutic strategies.”

2021 Impact Award   

Targeting Brain Cells That Cause Movement Disorders in Parkinson’s

Rafiq Huda, PhD, of Rutgers University received a Parkinson’s Foundation George G. Kaufman Impact Award to identify a potential therapeutic target for the motor symptoms of Parkinson’s disease (PD). Using cutting-edge technology, he will examine how an understudied group of brain cells called astrocytes contributes to motor dysfunction in PD. Astrocytes are an important component of brain circuits that regulate nerve cell processing.

“Astrocytes are fascinating cells that can do much more in the brain than they currently get credit for,” said Dr. Huda. “My hope is that what we discover in this basic science project will help establish astrocytes as a novel therapeutic target for PD.”

Movement requires coordinated activity across a large brain-wide network. Dr. Huda’s study will test whether astrocytes coordinate this network of activity in the striatum, a part of the brain that integrates motor-related information from many distinct brain regions to regulate movement. Dysfunction of the striatum, which is affected by the hallmark impairment of the production a brain chemical called dopamine in PD, is a key contributor to the disease’s motor symptoms. It is not known how the loss of dopamine affects the function of astrocytes.

Dr. Huda’s lab will focus on clarifying how astrocytes are affected and how their function impacts neuronal elements of the striatum. This research will work to explore how astrocytes contribute to motor symptoms of PD.  

“I wanted to focus my research efforts on topics that are directly relevant for improving the human condition,” said Dr. Huda. “Parkinson’s, and movement disorders generally, impact a significant number of people. Given my background in movement control, I figured I could make the most impact by focusing my lab’s energy on studying how dysfunction of brain processes underlie PD and other movement disorders.”

Of his Impact Award, Dr. Huda said, “The Award has already had a huge impact on the trajectory of my career. Going in new research directions is always very risky, especially with untested ideas. Besides providing financial support, receiving feedback from established and eminent PD researchers on our ideas was instrumental in sharpening our thinking about how to approach this project.”

2021 Impact Award    

Understanding Gender Differences in Parkinson’s

Biological sex has a strong influence on the symptoms and course of Parkinson’s disease (PD). Ellen Hess, PhD, of Emory University, a Parkinson’s Foundation Center of Excellence, received a Parkinson’s Foundation George G. Kaufman Impact Award to study sex differences in PD.

Previous research has established that males are two times more likely than females to develop Parkinson’s. Men also develop the disease at an earlier age than females and are more likely to have bradykinesia (slowness of movement). In later stages, men have increased daytime sleepiness.

“There are very few studies examining the underlying reasons for sex differences in movement disorders but our knowledge of sex differences in the biology of the central nervous system has grown in leaps and bounds in the past few years,” Dr. Hess said.

Women tend to have more Parkinson’s-related tremors. Women also have greater anxiety and depression, and more severe involuntary movements caused by the Parkinson’s medication levodopa. This is called L-DOPA-induced dyskinesias, or LIDs. Some research suggests estrogen may play a role in delaying or preventing Parkinson’s in women, but estrogen is probably not the only explanation for the differences between males and females.

“The biological reasons for the differences between the sexes are largely unknown and unexplored but nonetheless very important because understanding these differences could ultimately lead to personalized and more effective treatments that are targeted to males or females,” said Dr. Hess.

Dr. Hess’s research will examine sex differences in gene expression in basal ganglia in a mouse model of Parkinson’s and LIDs. The findings could lead to the discovery of drugs specifically targeted to male and female patients using a personalized medicine approach.

“Although I have been working in the role of dopamine in movement disorders for my entire scientific career, much of our work has focused on dystonia, this is actually our first grant on Parkinson’s disease,” said Dr. Hess. “The Parkinson’s Foundation grant is providing my laboratory the opportunity to expand the focus of our work and, for the first time, to contribute to Parkinson’s disease research in a meaningful way.”

2021 Impact Award  

Insights Into Brain’s Dopamine System Could Yield New Parkinson’s Treatments

Onur Basak, PhD, of University Medical Center Utrecht - Translational Neuroscience Utrecht, Netherlands, received a Parkinson’s Foundation George G. Kaufman Impact Award to investigate the role of histones (a type of protein found in chromosomes that bind to DNA) in the development and progression of Parkinson’s disease (PD). This research will yield insights into the dopamine system in the brain that may lead to new treatments for Parkinson’s.

Despite decades of research, we still do not know exactly how Parkinson’s disease develops. A major hallmark of the disease is the loss of brain nerve cells called dopaminergic neurons in two regions of the midbrain. These nerve cells produce the brain chemical dopamine. In people with Parkinson’s, the cells that make dopamine are impaired. Current treatment for loss of motor symptoms focuses on dopamine but cannot offer a cure.

“There is a great need for new therapeutic targets for PD. Our research provides a new perspective that has the potential to implicate new molecular processes that can be ‘hijacked’ for therapeutic approaches in the long run,” said Dr. Basak.

Evidence shows that a biochemical process called methylation of histones is altered in people with Parkinson’s. However, how this happens is not well understood. Dr. Basak will study histone methylation in different types of dopamine-related neurons as well as neighboring cells that are indispensable for their function.

As part of his research, Dr. Basak will look at the way epigenetics — the processes that help direct when individual genes are turned on or off — affect the progression of Parkinson’s. In the long run, this study will contribute to efforts to discover new drug targets for Parkinson’s treatment. 

“Investing in fundamental research is the key to finding new venues for treatment, and eventually, a cure for PD,” Dr. Basak said. “Highly ambitious projects can only be carried out with the support of donors supporting this vision, as the Parkinson's Foundation does. This grant will give me the opportunity to turn a highly ambitious aim into reality. Since the grant is prestigious, it will also support my integration in the PD community.”

2021 Stanley Fahn Junior Faculty Award  

Learning How Pesticides Impact Parkinson’s

Tim Sampson, PhD, of Emory University, a Parkinson’s Foundation Center of Excellence, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to understand how Parkinson’s-linked pesticides affect the gut microbiome, the complex community of bacteria and other microbes in the intestinal tract.

Studies suggest that people with Parkinson’s disease (PD) harbor distinct gut microbiomes. By identifying gut microbiome changes, the effects of those specific changes on the body, and interactions between environmental exposure and genetic factors, Dr. Sampson hopes to link how insecticides trigger these defects of the intestinal tract and trigger Parkinson’s symptoms.

“Going back 200 years to James Parkinson’s first description of the disease, he noted that individuals with the shaking palsy also had dysfunction in their gut,” said Dr. Sampson. “As the field grew to understand the complexity of gut to brain communication and the role of the indigenous microbiome in this communication, it was clear that this path might be involved in neurological diseases, such as PD.”

Exposure to pesticides is a leading environmental risk for many neurological diseases, including Parkinson’s disease. Symptoms in the gut, including constipation and inflammatory bowel disease, often occur before developing Parkinson’s motor symptoms.

The gut microbiome is one of the first parts of the body to interact with oral exposures, for instance, through eating foods with residual pesticides. However, little is known about how the gut and its microbiome respond to insecticides, and how these changes may specifically impact Parkinson’s.”

“We know that PD likely arises from a confluence of genetic and environmental factors,” said Dr. Sampson. “Our study hopes to better understand the etiology of PD by exploring the contributions of the gut microbiome to chemical exposures that trigger PD-like pathology. We hope that this will provide insight at the earliest stages of the disease to better prevent PD and develop new therapeutic targets.”