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What We Fund: $69.1M Toward Novel Efforts to Improve Mobility and Target Cellular Mechanisms Underlying PD

Two researchers in a lab

The Michael J. Fox Foundation (MJFF) announces 45 grants that total more than $69.1 million awarded in June and July 2024.  

Here we review some of the supported projects aiming to improve how Parkinson’s disease (PD) is detected and monitored, develop drugs that slow or stop its progression and treat the symptoms that reduce mobility and increase the risk of falls. See full list of MJFF funded studies. 

Finding ways to improve mobility in people with effects of freezing 

One profoundly disruptive symptom of PD is freezing of gait (FOG), which causes unintended stops while walking or turning and increases the risk for falls and serious injury. There currently are no treatments for FOG. A team of researchers led by Theresa Ellis, PhD, PT, at Boston University, are working to improve walking and prevent FOG in PD with a lightweight, wearable robotic device. Fitting around the waist and thighs, the device provides hip flexion support that helps eliminate FOG and improve walking. The team published proof-of-concept earlier this year, reporting on use of the device among one person with PD. With funding from the MJFF Freezing of Gait Program, they are expanding testing to 20 people with PD and FOG. If their study demonstrates the device is effective, they intend to collaborate with an industry partner on larger studies. 

Targeting the underlying biology that is disrupted in PD 

Various biological factors appear to play a role in the development of PD, including mitochondrial malfunctioning, inflammation and protein misfolding. Many of these biological factors are now being targeted for treatment development. In the latest round of funding, MJFF funded a range of these efforts: 

Inhibiting calcium accumulation to prevent PD: A build-up of calcium in dopamine neurons seems to make them vulnerable to environmental and genetic stresses, and studies have linked excess levels of calcium in neurons to the development of PD. Researchers led by Thomas Otis, PhD, at Lario Therapeutics are exploring whether blocking this calcium accumulation reduces PD-related symptoms or even prevents PD. They designed a drug that inhibits a pathway in the brain that leads to the calcium accumulation, and now with funding from MJFF, they will test its effects in lab studies. If the outcomes are positive, they plan to advance the drug into human trials.  

Removing dysfunctional mitochondria to protect dopamine neurons: As the powerhouses of the cells, mitochondria generate the energy cells need to function and survive. But in PD, mitochondria stop functioning properly and build up in dopamine neurons, leading to their degeneration. Based on studies that an enzyme called USP30 blocks the clearance of malfunctioning mitochondria, researchers at Misson Therapeutics led by Suhail Nurbhai, MB ChB, MRCP, are working to inhibit USP30 in people with PD. Supported by funding from MJFF, they are planning a month-long Phase I study comparing the effects the of the USP30-blocking drug MTX325 versus placebo in a small group of participants. If they find that MTX325 helps clear dysfunctional mitochondria and has beneficial effects, they will conduct larger and longer-duration studies to learn more about its potential to slow the progression of PD.  

Reducing inflammation to slow cognitive symptoms: To treat PD-related changes in the brain, a drug needs to be able to cross the blood-brain barrier. This protective membrane is crucial for keeping harmful substances out of the brain, but it also keeps out most therapeutic drugs. Researchers at University of Arizona, led by Torsten Falk, PhD, are working to improve the design of so-called “peptide-based” drugs to make them more stable and more effective at entering the brain from the bloodstream. Preclinical testing on their lead drug, called PNA5, suggests that it holds potential to protect against thinking and memory problems linked to PD by dampening inflammation in the brain. With backing from MJFF, the researchers plan to conduct additional testing to learn more about the effects of PNA5 in PD and identify biomarkers that can be used to monitor its efficacy. If these preclinical studies are successful, they then hope to advance PNA5 into human trials. 

These three projects were funded through the Parkinson’s Disease Therapeutics Pipeline Program. 

Harnessing inflammation insights to detect and treat PD: Inflammation in and around the brain increases the production of toxic compounds that damage the nervous system. Higher levels of these compounds have been linked to more severe PD symptoms. At the Van Andel Research Institute, researchers led by Lena Brundin, MD, PhD, have studied the kynurenine pathway that produces these neurotoxic compounds and found links between its activity and PD severity. With backing from MJFF, they aim to develop a kynurenine biomarker for monitoring PD and to test whether drugs that target the kynurenine pathway are effective for treating PD. 

Uncovering the early biological changes that lead PD 

An area of research called “multiomics” brings together data from areas like genomics, transcriptomics, epigenetics, proteomics and metabolomics. Integrating this information can offer researchers a fuller understanding of the molecular changes happening in the body over the course of a disease. With funding from MJFF, researchers led by Benoit Lehallier, PhD, at Alkahest plan to use multiomics to analyze plasma from individuals who donated while healthy but then went on to develop PD later in life. They are focusing on the earliest stages of PD, before symptoms, to learn more about the mechanisms driving its progression. Findings from this study, called the Chronos-PD Pilot, could lead to diagnostic tests for Parkinson’s and pave the way for innovative therapeutics for preventing the disease and slowing its progression. 


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.  

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