A compound that successfully reversed movement symptoms in one group of Parkinson’s patients had zero effect when given to a different group of patients carrying distinct genetic mutations – even though both groups were diagnosed with the exact same disease. That finding, from a May 2026 study published in Nature Communications, has led researchers to ask a fundamental question: what if Parkinson’s isn’t really one disease at all?
The implications are significant for the more than 10 million people worldwide living with a condition scientists now believe may consist of several hidden subtypes rather than one single disorder, with different biological forms responding differently to treatments. For decades, neurologists have treated Parkinson’s as a unified diagnosis, grouping patients together based on shared symptoms like tremors, stiffness, and slowed movement. The new research suggests that approach may have been masking crucial biological differences that explain why so many treatment attempts fail.
Numerous clinical trials using a wide variety of approaches have failed to achieve disease modification, and researchers have long suspected that the heterogeneity of Parkinson’s is a major contributing factor – and that it is unlikely a single treatment will be effective in all patients. The 2026 findings from Belgium offer one of the clearest molecular explanations yet for why.
What Researchers Found About Parkinson’s Disease Subtypes
A new study led by researchers from VIB and KU Leuven shows that Parkinson’s disease can be divided into distinct subtypes, helping explain why a single treatment does not work for all patients. Using a machine-learning-driven analysis, the team identified two main groups and five subgroups of the disease, marking an important step toward more personalized therapies. The findings were recently published in Nature Communications.
The research was led by Prof. Patrik Verstreken of the VIB-KU Leuven Center for Neuroscience, who noted that Parkinson’s disease affects millions of people worldwide and is traditionally defined by its clinical symptoms, including movement difficulties and progressive neurological decline. Despite being grouped as a single disorder, Parkinson’s can be caused by mutations in many different genes, leading to diverse underlying biological mechanisms.
As Verstreken explained, when clinicians or patients look at the disease, they see the clinical symptoms, which unify people with Parkinson’s. But at the molecular level, patients fall into subcategories – and that matters because one drug to target the different molecular dysfunctions in all Parkinson’s disease essentially doesn’t exist.
The Fruit Fly Model: Why Scientists Used It
The study’s methodology is unconventional enough to raise eyebrows. Rather than analyzing human patients directly, the team turned to fruit flies. The team studied fruit fly models carrying mutations in 24 genes associated with Parkinson’s disease. Fruit flies are widely used in neuroscience because their nervous systems share many important similarities with humans.
What made the approach different from prior work was a deliberate decision to set aside assumptions. Dr. Natalie Kaempf of KU Leuven, the first author of the paper, described the team’s approach: “We came in without any preconceived notions of how a specific mutation would affect our animal model. We took animals with mutations in any of those 24 different genes that are causing the disease, and we just monitored their behaviour over periods of time.” That allowed the scientists to identify clusters of mutant genes that separated into two main camps: one group affecting mitochondrial function with two subtypes, and a second with three subtypes involving a mechanism by which molecular cargo is transported across cellular membranes, helping to maintain the integrity of the proteome.
Researchers monitored the flies’ behavior over long periods and collected large amounts of data. That information was then analyzed using machine learning algorithms. Machine learning is a form of artificial intelligence that allows computers to detect hidden patterns in complex data, and it is increasingly being used in medicine because it can uncover relationships too complicated for traditional analysis.
The Genetic Roots of the Disease
Understanding why these Parkinson’s disease subtypes exist requires some background on the genetics of the condition. According to the Parkinson’s Foundation, Parkinson’s is the second-most common neurodegenerative disease after Alzheimer’s, and an estimated 1.1 million people in the U.S. are currently living with it. That number is projected to reach 1.2 million by 2030, with nearly 90,000 new diagnoses made in the U.S. each year.
Understanding what causes Parkinson’s starts at the cellular level. The disease develops when nerve cells involved in movement and coordination become damaged over time, specifically those in a region of the brain called the substantia nigra (a small area deep in the brain that helps control movement). The loss of substantia nigra dopaminergic neurons – nerve cells that produce the chemical messenger dopamine – is a key feature of Parkinson’s.
While the neuropathology of the disorder is reasonably well understood, its precise causes remain complex, making it difficult to aim therapy. According to MedlinePlus, familial cases – where the condition runs in families – can be caused by variants in genes including LRRK2, PARK7, PINK1, PRKN, or SNCA. The research team contends that Parkinson’s should now be thought of as a collection of similar conditions with diverse underlying biological mechanisms – a framing that aligns with what genomic science has long suspected but struggled to act on clinically.
The vast majority of Parkinson’s patients exhibit alpha-synuclein aggregates (clumps of a specific protein) in several brain regions, but there is also great variability in the neuropathology between individuals. That variability, for years treated as background noise in clinical research, turns out to be a meaningful signal.
What Two Groups and Five Subgroups Actually Mean
The two main groups identified by the Belgian team map to two different cellular failure modes. One cluster involves disruption to the mitochondria (the energy-generating structures inside cells), and a second involves problems with retromer and vesicle trafficking – the process by which cells transport and manage proteins, critical to keeping cells functioning cleanly.
Together, this unbiased strategy revealed previously hidden structure within Parkinson’s disease, showing that different genetic forms naturally cluster into distinct subtypes. By moving away from assumptions and letting patterns emerge directly from the data, the study provided a framework for understanding the biological diversity of the disease and guiding future research toward more precise interventions.
The complexity of Parkinson’s genetics has made it difficult to develop effective treatments, because therapies that target one specific pathway may not work for patients whose disease is driven by a different mechanism. Compounds that target specific molecular pathways ameliorate dopaminergic neuron dysfunction in a cluster-specific manner – giving drug developers a structural map of where each treatment is likely to work and where it isn’t.
Treatment Responses Differ by Subgroup
Genes within each cluster share a similar genetic interaction profile, and compounds targeting specific molecular pathways correct dopaminergic neuron dysfunction in a cluster-specific manner – data indicating that familial Parkinson’s and related forms of parkinsonism may fall into two broad functional groups.
As Verstreken put it directly in the published study: “When we took a first compound that cured subgroup A and tested it in subgroup B, the latter wasn’t rescued. Our study shows that you can make subgroup-specific drugs that have positive effects and are really specific to that subgroup.”
A “one-size-fits-all” approach to treating Parkinson’s patients may be fundamentally flawed. A drug tested in a large, mixed trial population could appear to fail simply because it was effective only in one subgroup – and that subgroup was diluted across the full sample.
Verstreken has suggested the practical path forward: “By having these subcategories, we can now go and look within that group of patients with those particular mutations, search for specific biomarkers, and develop drugs tailored to each group.”
Read More: The Surprising Link Between Dreams and Dementia or Parkinson’s Disease
Beyond Parkinson’s: A Model for Other Diseases
The same classification approach may have applications well beyond Parkinson’s. As Verstreken concluded: “The same principle can be applied to other types of diseases – diseases that are caused by mutations in a variety of different genes or environmental factors could be classified according to this principle.”
Many chronic diseases – certain cancers, autoimmune conditions, and other neurodegenerative disorders – are diagnosed based on how they look clinically, while the molecular mechanisms driving them vary considerably between patients. The unbiased behavioral screening method used in this study is designed to detect exactly that kind of hidden structure, which conventional diagnostic tools simply aren’t built to find.
What This Means for You
The study does not change how Parkinson’s is diagnosed or treated today. The work was done in fruit fly models, and translating findings from animal research to human clinical practice takes years of further study. When a treatment stops working or never worked in the first place, the reason may not be that treatment was inadequate – it may be that the treatment was designed for a biologically different form of the same disease.
While dopamine replacement therapies can reduce motor symptoms, current therapies do not modify disease progression for any patient, regardless of subtype. That remains the central unmet need. The subtype framework offers a credible path toward changing that, by ensuring future drugs are tested in – and developed for – the specific group most likely to respond to them.
For people living with Parkinson’s or caring for someone who is, the most practical step right now is genetic testing. Knowing which gene variants are present could eventually determine which treatment pathway – or which clinical trial – is the right fit. Ask your neurologist whether genetic testing for known Parkinson’s-associated mutations has been discussed as part of your care plan.
Disclaimer: This information is not intended to be a substitute for professional medical advice, diagnosis, or treatment and is for information only. Always seek the advice of your physician or another qualified health provider with any questions about your medical condition and/or current medication. Do not disregard professional medical advice or delay seeking advice or treatment because of something you have read here.
AI Disclaimer: This article was created with the assistance of AI tools and reviewed by a human editor.
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