Neuronal Alpha-Synuclein Disease Integrated Staging System (NSD-ISS) proposes a shift from symptom-based to biology-based definition of Parkinson’s disease.
A groundbreaking framework for defining and staging Parkinson’s disease based on its underlying biology, rather than by hallmark symptoms, has been proposed by an international group of patients, researchers, and industry leaders. Led by the Michael J. Fox Foundation for Parkinson’s Research (MJFF), the framework, called the neuronal alpha-synuclein disease integrated staging system (NSD-ISS), aims to redefine Parkinson’s disease and other disorders characterized by the abnormal accumulation of the alpha-synuclein protein. This new approach has the potential to accelerate therapy development and facilitate clinical trials for disease prevention.
Rethinking Parkinson’s Disease Classification
The proposed framework challenges the current classification of Parkinson’s disease, which is primarily based on clinical presentation and the presence of motor symptoms. Instead, the NSD-ISS focuses on the pathological accumulation of misfolded and aggregated alpha-synuclein protein in nerve cells, which occurs years before symptoms become apparent. By shifting the focus to the biological markers of the disease, researchers hope to develop a standardized tool that can be used by the scientific community to advance therapy development and improve clinical trial design.
The Role of Biomarker Advances
Advances in biomarker tests, such as the alpha-synuclein seed amplification assay (aSyn-SAA), have paved the way for a more objective definition of Parkinson’s disease stages. The aSyn-SAA test accurately detects the toxic protein in the cerebrospinal fluid of patients, even in those without overt motor symptoms. This breakthrough has prompted scientists to call for a reevaluation of Parkinson’s disease classification based on biological markers, including alpha-synuclein and dopamine loss.
Collaborative Efforts to Develop the Framework
The development of the NSD-ISS framework was a collaborative effort involving over 550 individuals and organizations across six continents. The international working group included neuroscientists, clinical experts, industry sponsors, nonprofit organizations, regulatory authorities, and patient representatives. By bringing together a diverse range of perspectives, the framework aims to provide a comprehensive and inclusive approach to Parkinson’s disease staging.
Understanding the NSD-ISS System
The NSD-ISS system proposes disease stages ranging from zero to six. In the earliest stages (0-1), aggregated alpha-synuclein is detected using the aSyn-SAA test, followed by the assessment of problems in dopaminergic neurons using an imaging test called DaTScan. As the disease progresses, patients develop motor and nonmotor symptoms that contribute to functional impairments. In the most severe stage (6), patients experience significant impairments and are no longer independent in daily activities.
Advancing Research and Treatment
The proposed framework offers a uniform definition of Parkinson’s disease stages, enabling more objective assessment and comparison of lab research and clinical trial designs. This will greatly facilitate the development of therapies for patients at every stage of the disease. By fostering innovation in clinical development, the NSD-ISS framework aims to make trials more efficient and streamline regulatory review. Researchers hope that this new approach will serve as a research accelerator, paving the way for next-generation treatments in Parkinson’s disease.
The proposed neuronal alpha-synuclein disease integrated staging system (NSD-ISS) offers a paradigm shift in the classification and staging of Parkinson’s disease. By focusing on the underlying biology of the disease, rather than relying solely on clinical symptoms, the framework has the potential to revolutionize therapy development and clinical trial design. With further research and collaboration, the NSD-ISS could provide a standardized tool to accelerate the development of treatments for patients at every stage of Parkinson’s disease. This groundbreaking approach brings new hope for improved outcomes and quality of life for individuals living with Parkinson’s.