The Michael J. Fox Foundation (MJFF) announces 123 grants that total more than $85.9 million awarded in December 2023 and January 2024.  

Here we review some of the supported projects aiming to advance our understanding of Parkinson’s disease (PD) and improve diagnostic tools and treatments. See full list of MJFF funded studies.  

Refining a Wearable Device to Improve Walking  

Among the primary challenges facing people with PD are the changes in movement that affect gait and balance. At Skip Technologies, a team led by Anna Roumiantseva, MBA, is applying its expertise with wearable robotics to help overcome this challenge. They have shown that their prototype designs can improve walking in people with PD, and now with a MJFF research grant, are developing a wearable, lightweight, powered hip device that improves gait. They plan to work with a small number of people with PD to design and evaluate the impact of the device on walking. If successful, they will pursue longer-term testing and a trial to evaluate whether it meaningfully improves quality of life.  

Seeking a Solution to Apathy in PD 

Loss of motivation and initiative, sometimes referred to as apathy, is a common symptom of PD. Social activities may no longer bring enjoyment, daily routines may require more energy and basic tasks may be difficult to start and complete. At Integrative Research Laboratories, researchers led by Joakim Tedroff, MD, PhD, have identified a chemical compound that potentially could be used to treat the thinking abilities that underlie apathy. Called IRL757, the compound would be used as an additional treatment, not as a replacement for existing PD treatments. The researchers have conducted preclinical testing of IRL757 and now, with funding from the MJFF Parkinson’s Disease Therapeutics Pipeline Program, plan to conduct a Phase I study to confirm its safety in humans and assess how it is processed by the body. 

Pursuing a Novel Mechanism to Improve Cognition 

The Parkin protein has wide-reaching neuroprotective activity, and a reduction in its activity has been linked to the development of PD symptoms, including memory or thinking (cognitive) problems. Researchers at Selonterra, led by Roman Urfer, PhD, have identified compounds that, through a novel gene expression mechanism, increase Parkin activity and improve cognition. With supplemental funding from the MJFF Accelerated Therapeutics Program, they now are advancing work on these compounds with the aim of conducting preclinical testing of those that are the most advanced and determining their safety for use in human study.  

Improving Mitochondrial Functioning in Early PD 

Research has linked malfunctioning mitochondria — the so-called “powerhouse” structures inside cells that make energy and play a role in cell signaling — to the development of PD. A team at Lucy Therapeutics led by Amy Ripka, PhD, has developed compounds to improve mitochondrial function and now they are testing their ability to act as disease-modifying therapeutics for both early and later stages of PD. Ultimately, they aim to optimize the most promising compounds for clinical trials and identify biomarkers to monitor their impact on mitochondrial function and PD progression. MJFF provided supplemental funding for this research through the Accelerated Therapeutics Program, allowing the researchers to build on their original project which was funded in 2022. 

Gaining Insights to Alpha-synuclein Changes 

Research has established that the alpha-synuclein protein malfunctions in PD, causing it to misfold and form toxic clumps in the brain. But why and how this happens remains unclear. To gain insight into the process, researchers led by Judith A. Steen, PhD, at Harvard University, plan to apply their novel FLEXISyn platform to isolate, quantify and identify the molecular changes that result in alpha-synuclein becoming dysfunctional. Previously, they used the FLEXISyn platform to attain molecular and mechanistic information that enabled drugs and biomarkers for Alzheimer’s disease, and they now aim to engineer it to serve the same purposes for PD. Funding for the research was awarded through MJFF’s Alpha-synuclein Post-Translational Modifications Quantification Program. 

Advancing an Imaging Tool for Alpha-synuclein   

A long-sought goal in PD is an imaging test capable of measuring the pathological alpha-synuclein that is a hallmark of PD. By revealing changes in alpha-synuclein levels in the brain, the test would play a critical role in clinical trials by making it possible to see if new drugs are working. Now, investigators at Merck led by Helen Mitchell, PhD, are moving closer to achieving that goal. With a supplemental research grant from MJFF, they are conducting clinical studies of a promising alpha-synuclein imaging test. Applying a new molecule discovered from the team’s previous MJFF grant, the investigators aim to demonstrate that the test successfully images alpha-synuclein pathology in people with PD and then improve it for use in clinical trials of drugs to reduce alpha-synuclein.  

Developing More Accessible Biomarkers 

The alpha-synuclein seed amplification assay (αSyn-SAA) enables accurate and early detection of PD, but it requires a relatively invasive lumbar puncture to obtain cerebrospinal fluid. A research team led by Brit Mollenhauer, MD, at University Medical Center Göttingen, is working to develop αSyn-SAAs that work with more easily obtained samples, including skin, blood and saliva. With funding through the Accelerating Biological Understanding and Therapeutic Translation for PD Biomarkers program, they are using an αSyn-SAA that they have developed to analyze skin sample biopsies from the MJFF Systemic Synuclein Sampling Study. They then plan to compare their results to the spinal fluid αSyn-SAA results. 

Detecting Early Parkinson’s with Proteomics  

Early detection of PD opens the door to new understanding of the underlying disease mechanisms and eventually treatment to prevent disease-related neurodegeneration. With a research grant from MJFF, researchers at Alkahest are using cutting-edge proteomics technologies to learn about the earliest biologic changes occurring in PD and improve understanding of its underlying mechanisms. The project, led by Benoit Lehallier, PhD, and called Chronos-PD, will analyze plasma from individuals who donated while without PD but who developed PD later in life, and then compare these samples to those of healthy controls.  

Filling Knowledge Gaps for Biological Staging  

In January, an international team of patient, research and industry leaders published the first iteration of a research framework for staging and defining PD based on its underlying biology. The framework’s proposed staging system — the Neuronal Synuclein Disease Integrated Staging System (NDS-ISS) — encompasses clinical conditions for which dysfunctional alpha-synuclein is the defining biological hallmark, so it not only applies to PD but also to dementia with Lewy Bodies (DLB). To learn more about how the NDS-ISS applies to DLB, researchers led by Dag Aarsland, MD, PhD, at King's College London and Stavanger University Hospital in Norway, are conducting a large-scale effort to categorize individuals clinically diagnosed with DLB — and for whom spinal fluid and DATscans are available — into the NDS-ISS. The study is leveraging the resources of the E-DLB Consortium, a collaborative network comprising over 30 specialized centers across Europe focused on clinical translational research on DLB.  

Supporting Digital Technology Use in Research 

Digital technologies — including sensors, devices and smartphone apps — for detecting and monitoring Parkinson’s can provide objective, sensitive, real-world measures of Parkinson’s. Researchers can use these patient-centric measures to guide the development of new therapies. With the growing number of these digital technologies, MJFF has provided research grants to two separate projects focused on constructing and maintaining open, searchable resource repositories of what is available. Both projects — one led by Anat Mirelman, PhD, at Tel Aviv University, and the other by Jessie Bakker, PhD, at the Digital Medicine Society — will facilitate standardization and knowledge-based decision support for researchers and clinicians and aid selection of fit-for-purpose tools.  

The Michael J. Fox Foundation continues to fund advances in technology and medicine to drive toward effective therapies that can prevent, slow or stop disease progression.   

You can be a part of that mission.   

The Parkinson’s Progression Markers Initiative (PPMI) is our landmark study on a mission to stop the disease. It is open to anyone over age 18 in the United States. Whether you have Parkinson’s or not, join the study that could change everything.   
   
Recently diagnosed with PD or live outside the U.S.? Connect with the PPMI team.