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Notes From Our Labs and Clinics
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Building Upon Research Leadership in Rating Scales: A Key to Studying Early Parkinson’s Disease Progression
To characterize the severity of Parkinson’s disease in each patient, doctors rely on rating scales — validated tools that measure the motor and nonmotor symptoms of the disease and the effect they have on a person’s daily living. In the clinic, rating scales are essential for tracking disease progression. In clinical trials and research, they are invaluable for studying the benefits of therapeutic interventions.
Although the first rating scales emerged in the 1960s, RUSH’s Christopher Goetz, MD, a pioneer in developing and refining these tools through research, gives credit to the teachings of a French neurologist who practiced more than 100 years prior.
“Today’s specialists owe a great deal to Jean-Martin Charcot, the most celebrated neurologist of the time, whose core observations related to Parkinson’s disease in the 19th century pushed physicians to define the many distinct features of the disease,” Dr. Goetz said. “Charcot’s teachings remind us that patients’ manifestations of Parkinson’s disease are always unique, individualized and highly personal in terms of priorities and nuances.”
In 2008 Dr. Goetz led the international effort to better capture the uniqueness of each patient’s disease in rating scales. This resulted in the Movement Disorder Society Unified Parkinson’s Disease Rating Scale, or MDS-UPDRS, now the most widely used international measure of Parkinson’s disease severity. The MDS-UPDRS has been officially translated into 25 non-English languages.
Dr. Goetz and his collaborators are now advancing research — utilizing sophisticated statistical modeling techniques — to better identify salient items in the MDS-UPDRS that are most subject to change in the very first phases of Parkinson’s disease. Their aim is to identify a shorter inventory that can be used to chart the impact of new interventions targeted at slowing the natural progression of the disease in the first five years after diagnosis.
“Our analyses may also reveal powerful indicators of presymptomatic Parkinson’s disease,” Dr. Goetz said. “Such items could be assessed in large populational or epidemiological studies aimed at identifying the disease earlier than is now possible.”
Seeking Relief for Apathy Following DBS Treatment: Notes From the Lab of Alana Kirby, MD, PhD
When people with Parkinson’s disease receive deep brain stimulation, or DBS, to treat motor symptoms of the disease, apathy — loss of motivation that is a common nonmotor symptom — can worsen after treatment.
Alana Kirby, MD, PhD, assistant professor in the Department of Neurological Sciences, and T. Celeste Napier, PhD, professor in the Department of Psychiatry and Behavioral Sciences, have partnered to seek solutions for patients who experience these troubling symptoms.
“People with apathy still enjoy doing things, but it’s harder for them to get going,” Dr. Kirby said. “Positive things don’t seem to be as necessary to pursue. Negative things don’t seem to be as necessary to avoid. It worsens quality of life and increases caregiver strain.”
Drs. Kirby and Napier and their team aim to determine the time course of apathy-like behaviors during and after DBS of the subthalamic nucleus in the brains of rodents. With philanthropic support, they are observing motivationdependent behaviors in groups of rats with Parkinson’s-like symptoms who undergo DBS. Natural behaviors, such as exploring new objects, burrowing and grooming, are being combined with training to perform a simple task for a food reward to form a group of tests to assess motivation.
“We cannot ask rats what they are feeling, so we carefully observe their behavior in performing tasks that mirror human activities that are worsened by apathy and how these behaviors are changed by DBS,” Dr. Kirby said.
Dr. Kirby is an expert in optogenetic stimulation (using light to control the activity of neurons), a leading-edge research technique that can be used in animal models to see precisely how DBS stimulation affects individual brain pathways. The subthalamic nucleus is a key hub in the brain that connects with brain areas that control movement, mood and motivation. Optogenetics allows Drs. Kirby and Napier to examine the role of each pathway independently and then put them back together. This provides complementary information to what is available in observations of people with Parkinson’s disease who have received DBS. This understanding will be useful in designing approaches to recognize and prevent apathy-related brain changes due to DBS.
“The power of optogenetics holds promise to allow clinicians to selectively stimulate pathways that improve mobility while other areas of the brain are left untouched,” Dr. Kirby said.
Donor support has enabled Drs. Kirby and Napier to gather enough evidence to apply for and successfully obtain an R21 Exploratory/Developmental Research Grant Award from the National Institutes of Health to identify biomarkers that can be used to predict when DBS may result in disorders of mood or cognition and how to improve DBS protocols to reduce nonmotor adverse effects.
Investigating Disease Pathology: Notes From the Lab of Bryan Killinger, PhD
The laboratory of RUSH’s Bryan Killinger, PhD, assistant professor in the Department of Neurological Sciences, continues to advance its work studying the behavior of alpha-synuclein, the protein that aggregates into structures called Lewy bodies in the brains of people with Parkinson’s disease and related neurodegenerative conditions. A recent area of the lab’s focus has been phosphorylated alphasynuclein, a specific form of the protein strongly associated with Parkinson’s. Little has been known about this form of the protein, even in the brains of healthy people — until now.
In a key publication this year in the international journal NPJ Parkinson’s Disease Dr. Killinger and his collaborators shared findings that phosphorylated alpha-synuclein normally accumulates in a brain structure called the olfactory bulb. Their unexpected finding is of great importance to the field because the Parkinson’s disease process has been hypothesized to begin in the olfactory bulb. This brain structure plays a central role in helping people process odors, and loss of smell is considered an early warning sign of Parkinson’s disease.
“We observed a ‘bad actor’ in the very spot of the brain where the disease process may begin,” Dr. Killinger said. “Our findings were corroborated by colleagues at Harvard, and we have been working with this team, utilizing their novel mutant mouse model, to expand on our findings.”
Reducing Falls and Inequities: Research Notes From Mitra Afshari, MD, MPH
Approximately 60% of people with Parkinson’s disease fall each year, resulting in hospitalizations and reduced quality of life. Most of these falls occur in people’s homes, where behavioral and environmental factors can be modified to reduce risks.
Mitra Afshari, MD, MPH, assistant professor in the Department of Neurological Sciences, seeks to improve health outcomes for people with Parkinson’s disease through technologyenabled care. She has been at the forefront of telehealth research in the field, even before the COVID-19 pandemic increased interest in telemedicine.
In a pilot of a virtual fall prevention program, Dr. Afshari and her team found telerehabilitation to be feasible and safe, resulting in patients making progress with physical and occupational therapy goals and reducing home safety hazards.
Dr. Afshari is currently working to enroll 33 patients in a subsequent study to evaluate a modified home-safety selfassessment tool for virtual home safety evaluations. The tool identifies common hazards and potential modifications to reduce the risk of falls, such as grab bars, motion-sensing lights and furniture risers.
“One of the biggest pieces we learned from the pilot study is that these virtual home tours are really successful across the board for Parkinson’s disease patients,” Dr. Afshari said. “We want to operationalize this and make it easier for people to follow.”
Preliminary data informed a submission to the journal Neurology Clinical Practice and an application for a K23 Mentored Patient-Oriented Research Career Development Award from the National Institutes of Health to study telehealth interventions at scale, combining recommended environmental modifications with behavioral modifications. Previously, Dr. Afshari received the prestigious 2022 Mentored Clinical Research Award from the Parkinson Study Group to advance this work.
Dr. Afshari also works on community outreach efforts to improve access to Parkinson’s disease care for communities that have historically received inequitable health resources. Dr. Afshari partners with David A. González, PhD, ABPP, neuropsychologist in the Department of Neurological Sciences, and Andrea Hernández, clinical research coordinator, to expand efforts to reach Spanish-speaking Parkinson’s disease patients and their families.
The group will host three webinars for this population, specifically regarding nonmotor symptoms of the disease. The webinars will feature local and national speakers and assess participants’ retention of knowledge through pre- and post-webinar quizzes.
Dr. Afshari also hopes to expand RUSH’s support group for Spanish-speaking patients with Parkinson’s disease and their care partners by spreading the word about the group within the clinic and the community.
RUSH Study of Prebiotics in Parkinson’s Disease Featured in Nature Communications
Backed by years of philanthropic support, a collaborative team of RUSH researchers has been a driving force in researching the links between gastrointestinal health and Parkinson’s disease. Around 80% of people with Parkinson’s report abnormal GI symptoms, and constipation can be one of the earliest signs of the disease.
In a 2023 publication in the prestigious journal Nature Communications RUSH researchers shared promising findings from a pilot study in 20 people with Parkinson’s. For 10 consecutive days, study participants ate a prebiotic fiber bar designed by faculty at RUSH and collaborators at Purdue University. The prebiotic mixture is specially formulated to support good bacteria in the gut that offset pro-inflammatory bacteria that are abundant in the GI tracts of people with Parkinson’s.
Participants in the pilot study found the bar helped decrease the severity of GI symptoms. The RUSH researchers plan to build on these studies — in a clinical trial conducted over a longer time period with more participants — to see if patients’ motor symptoms can improve through dietary supplementation with special prebiotics.
RUSH Celebrates 250th MR-Guided Focused Ultrasound Procedure
In 2019 RUSH became one of the first health systems in the nation to offer patients a minimally invasive procedure to treat essential tremor and motor symptoms of Parkinson’s disease. MR-guided focused ultrasound, or MRgFUS, is a nonsurgical procedure that focuses sound waves inside the brain to interrupt faulty circuits that cause tremors and related symptoms.
This year, RUSH physicians celebrated performing the health system’s 250th MRgFUS procedure. The landmark procedure was performed on John Roberts, whose tremor impacted his ability to perform everyday tasks such as eating, drinking and writing. The treatment significantly reduced his tremor and enabled him to enjoy his first cup of coffee in 10 years.
To learn more about his story, visit rush.edu/250-ultrasounds.
In Gratitude
Donor support fuels the progress we make in our clinics, labs and classrooms. Our strong community of supporters and friends advances our efforts to improve life for people with Parkinson’s disease and other movement disorders and their care partners while we look with hope toward a future cure for these conditions. Thank you for your ongoing partnership and commitment to our work.
To support the Parkinson’s Disease and Movement Disorders Program at RUSH or learn how you can continue your legacy of support through an estate gift, scan the QR code, visit rushgiving.com/pdimpact or contact:
