In the relentless pursuit to unravel the mysteries of Parkinson’s disease (PD) and the intricate biology of ageing, the scientific community is turning to a pivotal, yet often underemphasized, ally: non-human primates (NHPs). These models embody a unique convergence of evolutionary proximity to humans, physiological complexity, and behavioral repertoire, positioning them as indispensable systems to explore multifactorial neurodegenerative processes that have thus far eluded complete understanding. Recent calls within the research domain advocate for a strategic and ethically grounded expansion of NHP research, aiming to catalyze breakthroughs in therapeutic development for age-related neurodegenerative disorders.
Parkinson’s disease, a progressive neurodegenerative disorder characterized primarily by motor dysfunction and dopaminergic neuron loss in the substantia nigra, remains a formidable challenge for translational neuroscience. While numerous rodent models have contributed foundational insights, the translational gap persists, underscoring the limitations of these models in fully recapitulating human pathophysiology. NHPs, sharing closer anatomical, genomic, and neurophysiological traits with humans, offer a superior model to simulate the complexity of PD, including its motor and non-motor symptomatology, disease progression, and response to pharmacological interventions.
Central to this advocacy is the recognition that advancing therapeutic strategies necessitates more than just model availability; it requires a comprehensive ecosystem integrating sophisticated tools, cutting-edge resources, and robust ethical frameworks. Investment in the development of novel NHP models that precisely mimic human neurodegenerative trajectories is critical. Such models must incorporate the heterogeneity of PD presentations, encompassing genetic variants, environmental factors, and age-related vulnerabilities, to provide a more holistic platform for investigating disease mechanisms and testing candidate therapies.
Furthermore, the ethical considerations surrounding NHP research command meticulous attention. The cognitive complexity and social behaviors of these primates impose a moral imperative to ensure their welfare and minimize suffering. This necessitates the establishment of stringent ethical standards that govern experimental design, housing conditions, and enrichment protocols. Equally important is transparency and active public engagement, fostering societal trust and understanding regarding the essential role of NHPs in addressing pressing neurological health challenges.
The implementation of an international research consortium dedicated to NHP-based neurodegenerative research emerges as a strategic solution to amplify collaborative efforts, optimize resource allocation, and standardize methodologies. Such a consortium would serve as a hub for consolidating expertise across neuroscience, primatology, genomics, and bioethics, facilitating the exchange of knowledge and accelerating discovery. Pooling data and biological resources internationally would mitigate duplication and foster rapid iteration of experimental paradigms aligned with clinical relevance.
Modern neuroimaging modalities and neurophysiological tools uniquely synergize with NHP research. Techniques such as positron emission tomography (PET), functional magnetic resonance imaging (fMRI), and in vivo electrophysiology in awake, behaving primates provide unprecedented resolution into disease mechanisms at cellular and circuit levels. Coupling these approaches with advanced molecular profiling and gene editing technologies further enhances the capacity of NHP models to interrogate pathogenesis and therapeutic impact with translational precision.
The ageing process itself is a complex, systemic phenomenon influenced by genetic, epigenetic, and environmental factors, culminating in increased susceptibility to neurodegenerative diseases like PD. NHPs naturally manifest ageing phenotypes that parallel those in humans, including cognitive decline, motor dysfunction, and neuropathological hallmarks, making them ideal subjects to dissect the interplay between ageing and neurodegeneration. This naturalistic aspect is challenging to emulate in short-lived rodent models, highlighting the irreplaceable value of primates in ageing research.
In addressing PD and ageing, the integration of multidisciplinary perspectives—from molecular biology and systems neuroscience to behavioral science and ethics—within the NHP research framework is paramount. This holistic approach ensures that findings extend beyond isolated observations to form cohesive mechanistic models, ultimately informing the development of targeted, patient-specific interventions.
Moreover, technological advances in gene editing, such as CRISPR/Cas9, have opened avenues to engineer precise genetic mutations associated with familial and sporadic forms of PD in NHPs. This capability allows for creating models that mirror the genetic underpinnings of human disease, enabling investigation into gene-environment interactions and the evaluation of gene therapy strategies within a physiologically relevant context.
Funding agencies and governmental bodies are called upon to prioritize resource allocation towards these endeavors, recognizing the pivotal role of NHP research in bridging experimental findings and clinical application. Long-term investments are imperative to sustain colony maintenance, develop infrastructure, and nurture training programs dedicated to NHP neuroscience, ensuring a robust pipeline of skilled investigators.
Public outreach and education are equally vital components of this proposed paradigm. Transparent communication about the scientific necessity, ethical safeguards, and prospective benefits of NHP research fosters informed societal discourse and supports continued engagement. By demystifying research practices and outcomes, the scientific community can galvanize public support and counteract potential misconceptions or opposition.
The envisioned international consortium would also facilitate the adoption and harmonization of standardized protocols, ensuring reproducibility and comparability of findings across laboratories and countries. This standardization is critical to build a cohesive body of evidence that can more effectively propel translational pipelines and regulatory approvals for novel therapeutics.
In the face of escalating global demographic shifts towards older populations, the urgency of confronting neurodegenerative disorders intensifies. NHP research, when strategically expanded and ethically conducted, offers an unparalleled platform to dissect disease complexity and accelerate therapeutic discovery, ultimately aiming to alleviate the immense societal and economic burdens imposed by PD and related ageing disorders.
The confluence of biological relevant modeling, cutting-edge technology, ethical stewardship, and international collaboration predicates a new era of neuroscience research. Harnessing the unique capabilities of non-human primates holds the promise to unlock the mechanistic enigmas of Parkinson’s disease and the ageing brain, translating into tangible clinical advances that preserve function and quality of life in aging populations worldwide.
Subject of Research: Neurodegenerative diseases, Parkinson’s disease, ageing, non-human primate models
Article Title: Position paper: leveraging non-human primate (NHP) specificities to accelerate Parkinson’s disease and ageing research.
Article References:
Bezard, E., Anderson, R.M., Badin, R.A. et al. Position paper: leveraging non-human primate (NHP) specificities to accelerate Parkinson’s disease and ageing research. npj Parkinsons Dis. 11, 227 (2025). https://doi.org/10.1038/s41531-025-01088-8
Image Credits: AI Generated
