The Michael J. Fox Foundation (MJFF) announces 129 grants that total more than $40.2 million awarded in August and September 2024.  

Here we review some of the supported projects to develop therapies targeting the underlying biology of Parkinson’s disease (PD) and its symptoms, improve how PD is detected and measured, and increase awareness of PD resources and clinical research opportunities. See full list of MJFF funded studies. 

Testing novel therapies targeting PD biology 

As researchers learn more about the molecular changes that underlie PD, they are developing therapies to target these changes. Ultimately, therapies like these that target PD’s biology — and not just its symptoms — are the path to a cure. The disease-modifying therapies that MJFF backed in the latest round of funding included one targeting mutations in the LRRK2 gene and another targeting malfunctions in mitochondria: 

• Mutations in the LRRK2 gene were first linked to PD 20 years ago, and they are now understood to be the most common causes of inherited PD. The mutations typically hyperactivate LRRK2, triggering cellular dysfunction that leads to PD. There are several known ways to modulate LRRK2 activity for therapeutic benefit. Researchers at Schrödinger led by H. Rachel Lagiakos, PhD, are developing a drug to reduce LRRK2 activity using a less-studied approach with the hope that it retains beneficial effects while avoiding the potential lung effects seen with some LRRK2-inhibiting drugs in development.   

• Mitochondria are the powerhouses of the cells, generating the energy that cells need to survive. Mitochondria also help regulate cellular functions, including the flow of calcium ions into the brain. Studies have shown that mitochondria can stop functioning properly in PD, leading to a build-up of calcium ions. When this happens, mitochondria develop a large hole that leads to cell death and the loss of dopamine-producing brain cells. At NRG Therapeutics, researchers are developing a novel drug to prevent dopamine degeneration by stopping mitochondria from developing this hole. Led by Anthony Richard Rutter, PhD, they plan to test its safety in animal models of PD and identify ways to assess its effectiveness for preventing dopamine loss.  

Improving turning in people with freezing of gait 

Freezing of gait is a symptom of PD that causes a sudden inability to take steps or turn. It makes walking difficult and increases the risk of falls and injury. There are no approved, effective treatments for freezing of gait. A research team led by Martina Mancini, PhD, at Oregon Health and Science University, has developed a turn-specific physical therapy intervention for people with PD. Preliminary testing has indicated that the intervention may improve mobility, and specifically turning, during activities of daily life. Now, with backing from MJFF, the team will launch a six-week, multisite randomized clinical trial to assess the intervention’s effectiveness in reducing freezing of gait.  

Advancing biomarkers for measuring Parkinson’s 

A 2023 breakthrough biomarker made it possible to detect the misfolded alpha-synuclein protein that is a hallmark of Parkinson’s disease. Called the alpha-synuclein seeding amplification assay (aSyn-SAA), it detects whether PD pathology is, or is not, present in the body even years before symptoms become visible — something that was previously impossible in living people. Researchers now are working to optimize the aSyn-SAA — so that it is easier to use and capable of assessing the severity of the disease. They also are focused on developing additional biomarkers for other biological changes linked to PD. In the latest round of funding, MJFF awarded grants to advance biomarker efforts and potentially improve the usefulness of biomarkers for clinical trials testing PD therapies: 

• One limitation of the aSyn-SAA is that it requires spinal fluid, obtained from a relatively invasive lumbar puncture. A team of researchers led by Todd Levine, MD, at CND Life Sciences have developed a biomarker test that detects alpha-synuclein in easier-to-obtain skin samples. It also can be used to measure the amount of alpha-synuclein, so it holds potential for tracking the progression of PD over time. The researchers now plan to test the skin biomarker in a study involving 100 participants with different stages of Parkinson’s disease, from early to advanced disease, to learn more about its effectiveness for assessing changes in the progression of the disease. 

• DaTscan is an existing SPECT imaging tool that takes detailed pictures of the brain, focusing on the cells that produce dopamine. With DaTscan, researchers can detect if dopamine neurons are reduced. Loss of these neurons leads to the hallmark symptoms of PD. Under current practices, DaTscan can help confirm a doctor’s diagnosis, but it cannot diagnose Parkinson’s by itself or measure the severity of the disease. But researchers led by John Seibyl, MD, at Institute for Neurodegenerative Disorders have developed a strategy that builds on technological advances to overcome some of these limitations. They are planning a study to test whether their strategy improves the power of DaTscan, so that it can track changes in the rate of disease progression.  

• Gaining a fuller understanding of the different ways PD affects people is crucial for early and accurate diagnosis and for the development of effective treatments. Researchers led by Gilles Tamagnan, PhD, at XingImaging aim to use a PET imaging tool that visualizes changes in the dopamine pathway of the brain to collect data about PD. They are planning to perform PET imaging over the course of two years in people at different stages of the disease. By then analyzing these scans, they hope to learn more about the ways PD affects the brain, particularly early in the disease process.  

Raising awareness about PD resources and research opportunities 

There are many resources available to support people affected by PD and a variety of opportunities to participate in clinical research. But often people are not aware of them or only learn about them long after their initial diagnosis. Aaron Lord, MD, is leading an effort at the Clinical and Translational Science Institute at NYU Langone Health to raise awareness through a training program for community health workers, who serve as important links between health and social services and the community. The training program focuses on increasing community health workers’ knowledge of brain health and PD. It also focuses on equipping them with skills to advocate for research participation and engage with diverse communities. MJFF funding will help support the development, piloting, evaluation and scaling of the training program so that it can be integrated into community health worker training nationwide.  

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.