The Michael J. Fox Foundation (MJFF) devotes our donor-raised dollars to the most promising scientific efforts to bring new treatments and cures closer to patient hands. In December and January, MJFF funded 35 new grants totaling more than $11 million.
It includes a grant to continue the California Parkinson’s Disease Registry, which captures data on Parkinson’s throughout the state. Last year, the registry was nearly discontinued due to COVID-related financial priorities, but MJFF stepped in to grant extension funding for one year. Read more on this project and its impact.
Here, we review other select projects that recently received MJFF funding and how they are positioning the field to drive closer to cures and new therapeutic options.
Testing New Ways to Stop Parkinson’s
Patients’ greatest unmet need is a therapy to slow or stop Parkinson’s. Recent Foundation grants reflect our strategy of numerous shots on that goal to raise the likelihood of success. Five new projects are exploring ways to stop the cellular breakdowns seen in Parkinson’s to slow or stop disease.
- Tracking Drug that Improves Cognition: Anavex Life Sciences is testing a drug with the potential to slow or stop Parkinson’s. ANAVEX2-73 activates the sigma-1 receptor protein, which protects brain cells from harmful stress and toxic protein buildup. After ANAVEX2-73 showed improvement on thinking and memory in people with Parkinson’s disease dementia, the company is studying how the drug works in the brain through imaging scans and blood tests. This can help guide future trials. We previously funded Anavex for laboratory studies toward development of ANAVEX2-73.
- Targeting Parkinson’s Protein Clumps: Researchers believe preventing the alpha-synuclein protein from clumping in Parkinson’s brain cells is key to stopping disease progression. Two recently funded laboratory projects are developing strategies to protect cells from alpha-synuclein clumps that could join the 13 approaches currently in human studies. Fazel Shabanpoor, PhD, at The Florey Institute of Neuroscience and Mental Health in Australia, is testing if a brain-penetrating molecule attached to an antisense oligonucleotide (ASO) can help it enter the brain. ASOs are a new type of drug that can decrease production of a harmful protein, such as alpha-synuclein, inside cells, but ASOs are unable to reach the brain from blood. M. Maral Mouradian, MD, at Rutgers Robert Wood Johnson Medical School in New Jersey, is designing small-molecule drugs to reduce the production of alpha-synuclein, minimize its clumping, and prevent or slow down brain cell damage.
- Fixing the Cell’s Energy Source: Other scientists are developing ways to keep cells healthy by disposing of malfunctioning mitochondria (the cell’s energy factories). Failure of mitochondria to work properly may lead to cellular energy crisis that ultimately contributes to the onset and/or progression of Parkinson’s disease. Emily Rocha, PhD, at the University of Pittsburgh is testing a drug to decrease the amount of USP30 protein, and AcureX is advancing a new class of drugs to lower levels of the protein Miro1. Both USP30 and Miro1 block the cell from disposing damaged mitochondria, and these therapies may help correct that process and protect cells.
Uncovering More Ways to Stop Disease
Scientists continue to build on an already rich base of knowledge and potential treatments to better understand how Parkinson’s begins and progresses. That information can identify new routes to stop disease and guide the development of more effective drugs. Some recent projects are investigating proteins and pathways that play a role in Parkinson’s:
- Exploring Types of Alpha-synuclein: Hilal Lashuel, PhD, from Ecole Polytechnique Fédérale de Lausanne in Switzerland is using a new set of research tools to explore the different types and location of the alpha-synuclein protein in Parkinson’s brain tissue. A next step may be to compare findings with type of disease (e.g., later onset or more severe symptoms) to uncover connections that could help predict type of Parkinson’s disease and match volunteers to studies.
- Understanding the LRRK2 and Skin Cancer Connection: Other projects are looking at LRRK2, another protein linked to genetic changes in Parkinson’s. In one, Deanna Benson, PhD, at Mount Sinai in New York studies the relationship between LRRK2 and melanoma. Some people with melanoma have an increased risk of Parkinson’s and vice versa, which may be linked to LRRK2 gene changes. Benson argues that treatments to lower melanoma risk may also lower Parkinson’s risk. (Read more on Parkinson’s and skin cancer.)
- Profiling GBA Pathway: Multiple projects are investigating the GBA pathway (dysfunction is linked to the most common Parkinson’s genetic mutation). For example, Ziv Gan-Or, MD, PhD, at McGill University in Montreal is profiling changes in two genes (TMEM175 and CTSB) that may interact with GBA changes toward higher risk of Parkinson’s and earlier age of onset. Monther Abu-Remaileh, PhD, at California’s Stanford University is studying the impact of GBA gene changes on lysosomes, the “recycling system” of the cell that degrades damaged cell parts. More information on TMEM175 and CTSB and on lysosome activity could show scientists ways to correct dysfunction and stop disease.
Developing Tools for Earlier Diagnosis and Better Tracking
MJFF also funds the discovery of more accurate ways to diagnose Parkinson’s earlier. This round of grants included projects to develop tests for Parkinson’s onset and progression as well as measure inflammation:
- Sniffing Out Parkinson’s: Anecdotal accounts have described a signature smell associated with Parkinson’s, which arises from protein changes in sebum (oily secretions that moisturize and protect skin) and may be an early indication of disease. Yesse Technologies, Inc. will test whether technology-enabled smell sensors respond differently to sebum from people with Parkinson’s than control volunteers. This could potentially lead to a diagnostic test that can detect Parkinson’s before symptoms or distinguish it from other neurological diseases.
- Assessing Inflammation Response: Malú G. Tansey, PhD, at the University of Florida is stimulating immune cells with a viral pathogen to test if the response promotes inflammation, which is linked to Parkinson’s disease. This study will determine if changes in immune cell responses are an early event in Parkinson’s and whether they could be used as a tool to diagnose the disease or monitor its progression. (Learn more about inflammation.)
- Measuring Mitochondrial Breakdown: Wolfdieter Springer, PhD, at the Mayo Clinic in Florida is measuring activation of the mitophagy pathway, which eliminates damaged mitochondria. The process is disrupted in Parkinson’s, and measuring that change may help predict or track Parkinson’s.
In addition to the grants funded above, MJFF separately provides grants to the Aligning Science Across Parkinson's (ASAP) initiative's Collaborative Research Network and Global Parkinson's Genetics Program (GP2).
Foundation support also went to our landmark study the Parkinson’s Progression Markers Initiative (PPMI), which aims to better understand Parkinson's onset and progression to speed the development of new treatments. Take a short survey to see if you may be eligible to participate.