2017 Investigator-Initiated Projects

Browse summaries of the research grants supported by the Parkinson’s Disease Foundation, a division of the Parkinson’s Foundation, in 2017. Stay tuned for additional announcements throughout the year.

Translational Research Grants | $500,000

Aim to ease difficulties related to cognition, sleep and fatigue in Parkinson’s, topics selected as part of the our Community Choice Research Awards.

[+] Impact of a Novel Exercise Intervention on Executive Function and Sleep in People with Parkinson's

Amy Amara, M.D., Ph.D., University of Alabama at Birmingham

For many people, nonmotor symptoms such as cognitive difficulties and sleep problems, can be more disabling than motor symptoms. Currently-available medications are either ineffective in treating cognition and sleep or offer unwanted side effects. Other therapeutic options such as exercise are known to improve the motor symptoms of Parkinson’s, but have not been fully explored for cognition and sleep. This study will examine the impact of a 16-week exercise program, compared to no-exercise, on cognition and sleep in Parkinson’s. Before and after the program, participants will undergo cognitive and sleep testing to measure any changes. The goal of this research is to identify an exercise program that will improve cognition and sleep in people with Parkinson’s.

 

[+] Remotely-supervised Transcranial Direct Current Stimulation (tDCS) for At-home Treatment of Fatigue and Cognitive Slowing in Parkinson’s Disease

Milton Biagioni, M.D., New York University

Currently, there are no effective treatments available for fatigue and slowed thinking, both of which are common symptoms in Parkinson’s. This study is testing an at-home brain stimulation device, along with cognitive training, to see if the dual-therapy can ease both symptoms. The stimulation, called transcranial direct current stimulation (tDCS) is a low-cost, relatively safe noninvasive brain stimulation technique that can be used at home. The cognitive training sessions are computer-based exercises designed to strengthen cognitive abilities. The study will offer the therapies online, using telemedicine, enabling people who have trouble getting to the clinic to participate from home. The results will help us to understand if the treatment works and will guide future brain stimulation research to validate this therapy for fatigue and slowed thinking.

 

[+] Goal-directed Behavior in Parkinson's Disease

Nabila Dahodwala, M.D., University of Pennsylvania

Cognitive impairment and apathy are common symptoms that can be disabling for people with Parkinson’s and their care partners. Our hypothesis is that people may experience both symptoms, as a result of fewer “goal-directed behaviors.” Goal-directed behaviors are activities done with purpose (for example, reading a book) versus habits or reactions, such as automatically laughing at a joke. This study will test a new way of measuring goal-directed behavior in Parkinson’s. It will also use brain imaging to observe brain changes that occur when people experience apathy and cognitive impairment. The hope is that the study will shed light on the mechanisms underlying apathy and cognition in PD, and help in more easily diagnosing them. This knowledge ultimately will allow for the development of targeted treatments for people with Parkinson’s.

 

[+] Multi-modal Neuroimaging of Fatigue in Parkinson’s Disease

Hengyi Rao, Ph.D., University of Pennsylvania

[+] Double-blind, Randomised, Cross-over, Pilot Study of Cannabidiol in People with Parkinson’s and RBD Sleep Disorder

Renata Riha, M.D., University of Edinburgh

Stanley Fahn Junior Faculty Awards | $300,000

[+] Direct Imaging of the Cause and Treatment of Parkinson's Disease with Synthetic Modulatory Neurotransmitter Nanosensors

Markita Landry, Ph.D., University of California, Berkeley

Parkinson’s disease develops when levels of the chemical messenger dopamine decline in the brain. Standard PD therapies work by raising dopamine levels. However, there is to date no way to measure changes in these levels quantitatively – for example, to understand how well a drug works. That’s because dopamine is difficult to detect in the brain and because the area affected by PD is deep within the brain and difficult to scan. In studies with mice, we are developing new infrared dopamine nanosensors that can detect the brain’s use of dopamine in real time — in the short term, such as after a physical therapy session or after a dose of medication, as well as throughout long-term disease progression. Our goal with this imaging technique is to provide a quantitative basis for evaluating drug effectiveness and dosing, rather than relying on trial and error and observation of symptoms.

 

[+] Deconstructing the Behavioral Neuropharmacology of Parkinson’s Disease

Michael R. Tadross, M.D., Ph.D., Duke University°

Many scientists are trying to develop drugs to circumvent the side effects of standard PD medications. But their efforts have been stymied by the fact that the brain area affected — the striatum — consists of many different types of cells, all tightly intermingled. The non-dopamine therapies have helped some cell types while harming others, canceling out any benefit. We are using a new method called DART (Drugs Acutely Restricted by Tethering), which ensures that a drug is sent only to one isolated cell type. With this technique, we are mapping which cell types receive a benefit and which are responsible for side effects for several classes of drugs. Ultimately, the results will reveal insights into the causes of Parkinson’s and will guide development of new targeted therapies.

 

[+] In Vivo Systems-Based and Unbiased Approaches to Study Alpha-Synuclein Toxicity

Maxime Rousseaux, Ph.D., Baylor College of Medicine°

In Parkinson’s disease, abnormal forms of a protein called alpha-synuclein form clumps within the brain’s dopamine neurons. The clumps, called Lewy bodies, are a hallmark of PD, and they are associated with cell death. But scientists know little about what happens after a cell produces alpha-synuclein – what substances does it interact with, and why does it clump together? Using new genetic and protein-screening technologies, we will identify proteins that bind to alpha-synuclein and increase or decrease alpha-synuclein levels. This, in turn, will shed light on how alpha-synuclein becomes toxic. We will focus on proteins that are known to be altered in PD, and that can be targeted by conventional drugs. This will lead us to a handful of promising candidates for new PD therapies, which can then be tested in the laboratory.

 

Postdoctoral Fellowship Awardees | $275,000

[+] White Matter Templates in Parkinson’s Disease

Derek Bradley Archer, Ph.D., Mentor: David Vaillancourt Ph.D., University of Florida

Scientists studying Parkinson’s disease are searching intensely for a biomarker—a blood test, brain scan, or other objective measurement — that can definitively diagnose Parkinson’s and be used to monitor disease progression. Some of this research focuses on analyzing specific brain regions in people with Parkinson’s disease. But the nerve fibers that connect brain regions, known as white matter, or tracts, also are important. We will use a scanning technique called diffusion MRI to create a map of the brain tracts affected by Parkinson’s disease. Then we will use this map to assess Parkinson’s and its progression in 151 individuals living with the disease, and compare the results with scans from 87 healthy individuals. Ultimately, we aim to develop a way to quantify brain changes associated with Parkinson’s, in order to improve diagnosis and treatment.

 

[+] D620N VPS35 Knockin Mice: A New Model of Familial Parkinson’s Disease

Xi Chen, Ph.D., Mentor: Darren Moore, Ph.D., Van Andel Institute

In a small percentage of cases, genetic mutations directly cause Parkinson’s disease. One gene that can cause Parkinson’s disease is known as VPS35. Little is known about how the VPS35 protein interacts with other proteins in nerve cells. We will genetically engineer laboratory mice to have a mutated VPS35 gene that is similar to the mutated form found in humans. We will study motor symptoms, dopamine levels, loss of dopamine neurons and other brain cell changes in these mice. We also will investigate how VPS35 interacts with two other proteins involved in Parkinson’s – tau and alpha-synuclein. Understanding these interactions could help us to develop new drugs that interfere with the actions of either or both proteins to prevent or treat PD.

 

[+] Mitochondrial Protein Homeostasis in Peripheral Axons

Jill Falk, Ph.D., Mentor: Thomas Schwarz, Ph.D., Harvard Medical School/Children’s Hospital Boston

Mitochondria are the powerhouses of cells — tiny structures that produce energy from nutrients. Neurons, including the brain cells affected by Parkinson’s disease, require lots of energy in order to exchange signals with other neurons. So these cells are constantly replenishing their mitochondria. Cells affected by Parkinson’s disease have trouble disposing of damaged mitochondria, and much research has focused on this. Our project investigates the supply end of the process — how do cells replace worn-out mitochondria with healthy new ones? This is a particular challenge for neurons because these structures are made in the central cell body and must be distributed evenly throughout the long cellular “arms,” or axons, that stretch out to connect with other neurons. Finding ways to improve the supply of healthy mitochondria to axons could lead to new Parkinson’s disease therapies.

 

[+] Expanding Human Dopamine Neuronal Progenitors for PD Therapeutic Development

Xiang Li, Ph.D., Mentor: Su-Chun Zhang, Ph.D., University of Wisconsin-Madison

Parkinson’s disease develops when brain cells that normally produce the chemical messenger dopamine sicken and die. Among the approaches to treating the disease – as opposed to current therapies which treat and mask symptoms – are to develop therapies that rejuvenate sickened cells by slowing or preventing their death, or to replace the dying cells with healthy ones. Both approaches will require large quantities of dopamine neurons of uniform quality. To meet that need, we will develop a “cocktail” that will allow us to grow billions of dopamine neurons starting with relatively few human pluripotent stem cells — cells that have the potential to develop into different cell types. Then we will test the cells to be sure they function as dopamine neurons. Ultimately, our goal is to produce a reliable supply of dopamine neurons that can be used in laboratories to develop new therapies, or in clinical studies of cell transplant therapy.

 

[+] Role of Cerebellum on Basal Ganglia Cortical Network in Parkinson's Disease

Nicholas Strzalkowski, Ph.D., Mentor: Zelma Kiss, M.D., Ph.D., F.R.C.S.C., University of Calgary, Canada

In Parkinson’s disease, miscommunication between the nerve cells in different parts of the brain leads to movement difficulties. Recent studies suggest that a part of the brain called the cerebellum is involved in tremor. This study will investigate the role of the cerebellum in relation to two other brain areas, the basal ganglia and the motor cortex, and how this affects tremor. We will study people who have recently undergone surgery for deep brain stimulation, a PD treatment in which electrodes (wires) are implanted in the basal ganglia. While recording basal ganglia activity, as well as signals from the motor cortex (with electrodes placed on the scalp), we will measure arm movement before and after temporarily shutting down activity in the cerebellum. A better understanding of the role of the cerebellum in Parkinson’s disease may contribute to new therapies.