2021 Stanley Fahn Junior Faculty Award  

Exploring Brain Chemicals’ Role in Parkinson’s Cognitive Decline

Scott Owen, PhD, of Stanford University, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to study, understand and restore cognitive function in mouse models of Parkinson’s disease (PD). These findings could lead to more effective, targeted treatments for PD.

Many people with Parkinson’s not only experience loss of motor function and slowing of movement, but also experience cognitive changes including impulsive behavior and reduced capacity for flexible learning — the ability to adapt to a changing environment. While pharmacological and surgical treatments can be effective for treating motor symptoms, there is a critical need for better treatments for cognitive symptoms.

“Changes in cognitive function are comparatively poorly understood, but can be life-changing and debilitating,” said Dr. Owen. “By investigating mechanisms underlying these changes using mouse models, and how these mechanisms respond to common treatments including Levodopa and deep brain stimulation, our goal is to build a fundamental understanding of the underlying biology that can be used to modify, develop and innovate future treatments that are tailored to improve cognitive function.”

Research suggests Parkinson’s symptoms arise from an imbalance between two key brain chemicals, dopamine and acetylcholine. Elevated levels of acetylcholine are essential for flexible learning in the healthy brain, but it is not known whether or how disruption of the relationship between dopamine and acetylcholine contributes to the deficits that are observed in Parkinson’s.

Dr. Owen will investigate where and how acetylcholine acts in the brain to facilitate flexible learning, and how this pathway is altered following the loss of dopamine.

“New tools are emerging and driving discovery in neuroscience at an accelerating rate, making this a particularly exciting time to be in the field,” said Dr. Owen. “Multiple innovations are on the horizon targeting all aspects of Parkinson’s disease from diverse standpoints. I am exceptionally enthusiastic about the potential of this work for guiding future treatments of Parkinson’s and gaining a deeper understanding of brain function.”

Of his grant award, Dr. Owen said, “The award from the Parkinson’s Foundation is an absolutely invaluable jump-start for this project. In addition to directly supporting a specific project, this early funding can have a “multiplier” effect by establishing the foundation for a sustained, large-scale effort focused on Parkinson’s research in my lab in the future. Building on the support from the Parkinson’s Foundation, I anticipate that this work will be a core focus of my lab for many years.”

2021 Stanley Fahn Junior Faculty Award  

Protecting Midbrain Neurons to Delay or Treat Parkinson’s

Lindsay Mitchell De Biase, PhD, from the University of California, Los Angeles, received a Parkinson’s Foundation Stanley Fahn Junior Faculty Award to gain a better understanding of the role of central nervous system immune cells called microglia in Parkinson’s disease (PD). Ultimately, this work could lead to therapies that delay or treat Parkinson’s.

Microglial cells can shape neuron function and health and remove debris from surrounding tissue. They regulate the signaling connections between neurons (called synapses). They also regulate central nervous system inflammation. Previous research suggests structures within the cell called mitochondria may be able to regulate the function of midbrain microglia and their responses to aging.

“Many gene mutations that increase the risk for Parkinson’s are mutations in genes related to mitochondrial function,” said Dr. De Biase. “We think that some of these mutations are increasing disease risk, not only by affecting energy production within neurons but by pushing microglial into a damaging, inflammatory state.”

Dr. De Biase’s goal is to determine if manipulating the function of microglia can protect midbrain dopamine (DA) neurons, which regulate movement and play an important role in the progression of PD. Currently, there is no way to protect these brain cells.;

“Microglia are dynamic, malleable cells and could represent therapeutic targets that are highly distinct from many that have been explored thus far,” said Dr. De Biase.

Microglia are different in the midbrain compared with other brain regions, Dr. De Biase discovered. During aging, they multiply. They release inflammatory factors earlier than microglia in other brain regions. This creates early “pockets” of inflammation that are likely to interfere with synapse function and neuron health.

These findings suggest that the unique traits of midbrain microglia are key to making DA neurons more vulnerable to Parkinson’s. Discovering what makes these microglia more responsive to aging and disease holds great promise for harnessing these cells to protect DA neurons.

Using new technology, Dr. De Biase will seek to better understand the role of microglial mitochondria in a mouse model of Parkinson’s disease. The intervention strategy she develops could be used in people who are at high risk for developing the disease, to delay or prevent disease onset. In people with PD, it could be used to create a more neuroprotective environment, preserve remaining dopamine neurons, and hopefully, delay disease progression.

Dr. De Biase has taken inspiration in her work from her father, a retired physician, who at times expressed frustration about the limits to what treatments he could offer and was envious of researchers who work to advance scientific knowledge.

“I have always hoped that my research efforts can benefit human health,” Dr. De Biase said. “We clearly need both clinicians and researchers. Even if I can’t meet with patients directly in a consultation room, I am hoping that our research can go on to help numerous people out there who each have their unique stories and struggles with the disease.”

Of the Parkinson’s Foundation grant, Dr. De Biase said, “This award has been absolutely instrumental in giving us the support to pursue these studies. I am a relative newcomer to the field of Parkinson’s research. This award will help us secure additional funding to continue pushing forward in this research direction. Interacting with other researchers and individuals living with PD through the Foundation is also enormously beneficial to our efforts.”

2021 Postdoctoral Fellowship 

Solving Sleep Problems Related to Parkinson’s

Daniel Silverman, PhD, of the University of California, Berkeley, received a Parkinson’s Foundation James R. "Jim Bob" Moffett, Sr. Postdoctoral Fellowship grant to study the mechanisms that contribute to sleep disturbances in Parkinson’s disease (PD). This could lead to innovative treatments or preventative measures to improve this common side effect of PD.

Sleep problems sometimes act as an early warning sign of PD before movement deficits set in and may severely impair quality of life.

Sleep can also be negatively impacted by medications that treat other Parkinson’s symptoms, which affect levels of brain chemicals called dopamine and norepinephrine. Brain nerve cells (or neurons) that release these chemicals are also involved in regulating sleep and are among the first neurons to deteriorate in Parkinson’s. The relationship between sleep problems and nerve cell degeneration is not well understood.

Dr. Silverman, who developed novel approaches for revealing the mechanism of retinal degeneration and night blindness from a rhodopsin (light-sensitive receptor protein) mutation in graduate school, was drawn to Parkinson’s research based on the work of Berkeley neuroscientist Yang Dan, PhD.

“After seeing Dr. Dan’s research on sleep, I became curious — often thinking about sleep experiments lying awake at night,” said Dr. Silverman. “It was striking to learn that little is known about the mechanisms that control the brain’s balance between wakefulness and sleep, especially because disruption is a common symptom of Parkinson’s disease.”

Dr. Silverman will focus on the role of molecules called reactive oxygen species (ROS) in PD sleep problems. Emerging evidence has shown that reactive oxygen species build up when neurons release dopamine and norepinephrine. Research also shows these neurons are inhibited by high levels of ROS.

Using a mouse model, Dr. Silverman will try to determine if ROS levels grow during long periods of being awake and whether quality sleep may help cells to recover from the stress caused by ROS. “With a better understanding of the molecular dysregulation that underlies sleep disturbances in Parkinson’s, a targeted treatment could one day aim to restore healthy sleep,” said Dr. Silverman.

2021 Postdoctoral Fellowship 

Neurons in Basal Ganglia Could Play Key Role in Parkinson’s Motor Symptoms

Connor D. Courtney, PhD of Northwestern University Feinberg School of Medicine (a Parkinson’s Foundation Center of Excellence) received a Parkinson’s Foundation Postdoctoral Fellowship grant to study a part of the brain that plays a key role in Parkinson’s disease (PD) motor symptoms called the external globus pallidus (GPe).

GPe nerve cells, located in a region deep in the brain called the basal ganglia, are key to movement, perception, and judgment.

Dr. Courtney recently discovered that two types of brain nerve cells (neurons) in the GPe serve opposite roles in regulating motor response. He will investigate the role of brain cells called astrocytes in regulating these two cell types. He believes that interactions between GPe neurons and astrocytes may be critically disrupted in PD.

“This award enables me to lay the foundation necessary to unravel the complex roles astrocytes are likely playing in PD,” said Dr. Courtney. “Shockingly little is known about how these intriguing cells contribute to the development of symptomatology of PD, and learning more about them may pave the way for important PD therapies in the future.”

Dr. Courtney attributes his motivation to study Parkinson’s disease to his father, who currently lives with PD. “As an issue with tremendous personal relevance, my overarching aspiration is to take my deep passion for neuroscience and apply it to the study of PD,” said Dr. Courtney. “I am exceedingly grateful to the donors and supporters of the Parkinson’s Foundation! It is an honor to be supported by a foundation that means so much to my family.”

Joe Dunn, newly named Reach Further campaign co-chair for the Parkinson’s Foundation Heartland chapter, attributes his desire to support Parkinson’s disease (PD) research to his late grandmother’s 10-year battle with the disease.

Further inspired by the ambitious goals set forth in the Reach Further campaign, which include raising an additional $30 million to advance research and expand care and community programs, Joe and the Dunn Family also pledged a leadership campaign gift of $250,000.

The campaign’s emphasis on expanding PD GENEration: Mapping the Future of Parkinson’s disease, which will provide up to 15,000 people with PD no-cost genetic testing and counseling, is particularly impactful for Joe and his family.

“This campaign, and its focus on genetic research, is really important to the family because we are at risk later in life,” said Joe. “The reason I stepped up is because this focus on identifying the genetic factors of PD is something I think lots of people will want to get behind and donate towards, and I want to be part of that."

As Reach Further regional co-chair, Joe will lead campaign fundraising efforts within the Parkinson’s Foundation Heartland Chapter and will work to inspire others to support the campaign’s critical goals.

Joe, who lives in the Kansas City area, close to top medical providers, is passionate about the Reach Further campaign’s focus on expanding quality neurocognitive care into the rural regions that the Heartland chapter encompasses.

“Across the country, access to specialized care in rural areas is a huge issue. My grandmother had a top movement disorder specialist who is director of the Parkinson’s Foundation Center of Excellence at the University of Kansas Medical Center. Many others don’t have access to such high-quality medical attention but lots of people with PD would like access to that level of care.”

For Joe, the Foundation’s three-priority approach to research, care and community support also matters tremendously. “The thing that sets the Parkinson’s Foundation apart is the community outreach and education pieces,” said Joe. “Ultimately, you need a holistic approach to deal with a complex disease like PD.”

Joe recalled that prior to his grandmother’s passing in 2013, there was much uncertainty around her diagnosis, as well as a hesitance to share her struggles with her family. “For the longest time, no one knew what she had,” Joe said. “She was hunched over for the last five years of her life, but did not talk openly about it. She was embarrassed that she needed help. This is why I feel so strongly about creating awareness and acceptance around PD, in her memory.”

Joe offered the following advice to other families who are dealing with Parkinson’s: “The biggest thing is to be supportive and be patient. A lot of people don’t want others to know what’s going on, but be supportive anyway you can, and be proactive about reaching out for resources and help. The Parkinson’s Foundation is a great place to start.”

Join the Dunn Family in helping us Reach Further.

Donate and check our campaign progress at Parkinson.org/Reach

Movement disorders specialist Leila Montaser Kouhsari, MD, wanted to become a neurologist at six, after losing someone she loved and admired. Her grandfather, Mohsen Ziaei, passed away after a devastating car accident left him in a coma, with no brain activity.

“I learned in a very difficult way that if your brain isn’t functioning, you cannot survive,” Dr. Montaser Kouhsari said, who today practices medicine at Stanford Neuroscience Health Center.

Not many can say their career path held true from childhood, but for Dr. Montaser Kouhsari, it did. Throughout medical school, graduate school and her fellowship, she pursued her passion of neurology. Taking it a step further, she kept gravitating towards Parkinson’s disease (PD) — and movement disorders — as a specialty.

“During my training, I met a lot of people with different neurological diseases,” she said. “I found that patients with Parkinson’s were all really nice and always left me inspired by how much they wanted to do everything in their power to help manage their disease and help themselves. I was able to connect with them on that level.”

During her fellowship, she researched the role dopamine plays in cognition (decision-making, motivation, learning and cognitive control) “I thought with my research, I could be useful to this particular group of patients. I ultimately chose Stanford because I could continue my research and help patients.”

Dr. Montaser Kouhsari’s ongoing research can change the future of how we treat cognition symptoms in Parkinson’s. Today, she is working to identify a biomarker (an identifier that can be used for diagnosing Parkinson’s and tracking disease progression) that would monitor cognition changes.

“With current neurological testing, we cannot identify which people with Parkinson’s will develop cognitive impairment,” Dr. Montaser Kouhsari said. “We don’t have a biomarker to assess the progression of the disease or cognitive symptoms. With more advanced testing, we can bring neuroscience testing tools, such as those I developed during my PhD, to nail down cognitive symptoms much earlier on and offer treatment earlier in the disease. This is important because people with Parkinson’s are more at risk of cognitive impairment and dementia.”

In addition to her research, Dr. Montaser Kouhsari regularly treats patients with Parkinson’s, a skill she likens more to an art.

“As neurologists, we need to have a very good rapport and be very observant. Every patent is different — we rely on the history they give us, so we can treat their symptoms and their needs. With this disease, we see our patients over many years and we build a relationship with them and their families, which is very beautiful. You become part of the family. It’s a privilege to be able to join them on this journey,” said Dr. Montaser Kouhsari.

When it comes to answering all her patient’s questions, she often refers them to the Parkinson’s Foundation. “I always use the Parkinson’s Foundation. When people have questions and need resources and materials, or if they’re looking for exercise or support groups, I always point them there. If they want to volunteer or donate, I also advise for them to contact the Foundation.”

Dr. Montaser Kouhsari believes in the work of the Foundation, which why she serves on the Parkinson’s Foundation California Chapter Board. “Throughout my training and career, I have always heard that the Parkinson’s Foundation funds research and fellowships. I am excited to be on the board and look forward to joining the Parkinson’s community at local events.”

When it comes to being a female movement disorder specialist who is part of a neurology division that is majority female at Stanford and treating women with Parkinson’s (who often are not adequately represented when it comes to Parkinson’s), Dr. Montaser Kouhsari shares her keen observations.

“I can relate to our female patients with Parkinson’s,” she said. “It can be really hard to be a mom and a wife, and having Parkinson’s makes it difficult to fulfill so many responsibilities. I’ve had patients whose families are so supportive — and patients whose families didn’t know how much their mother/wife would be affected by the disease. I think it’s important to be more attentive to our female patients and offer more help.”

When it comes to everyone living with Parkinson’s, as a neurologist, Dr. Montaser Kouhsari’s advice is to “really listen to your body. Your doctor can help provide information about your symptoms and how they relate to medications and your progression, but be observant of your symptoms. We really need as much information as possible to provide the best treatment.”