TMCnet News
Patient, Research and Industry Leaders Propose Biological Definition and First Biological Staging for Parkinson's Disease
NEW YORK, Jan. 23, 2024 /PRNewswire/ -- Today, an international working group has proposed a new research framework — the neuronal alpha-synuclein disease integrated staging system (NSD-ISS) —that, for the first time, stages Parkinson's disease (PD) and defines it based on the disease's underlying biology. The paper, published in The Lancet Neurology, describes the framework, its applications, gaps in knowledge and future plans. The NSD-ISS framework is considered a milestone for the field, and a critical starting point — as more data is developed, its concepts and definitions are expected to evolve. The foundation of NSD-ISS defines Parkinson's by the presence of its hallmark pathology, neuronal alpha-synuclein (asyn), that can now be detected by reliable biomarkers, often before symptoms appear. By applying an objective approach to detecting PD and standardizing its tracking on a biological continuum, NSD-ISS represents a major leap into the new and emerging biological era of Parkinson's science. The new research framework stands to accelerate and increase the success of scientific discovery and therapeutic development at all stages of Parkinson's. And ultimately, a treatment that targets the biology of the disease — rather than just its symptoms — is the way to reach a cure. (A similar biological framework in Alzheimer's disease resulted in successful trials and new drug approvals, with the first drugs to slow Alzheimer's-related cognitive decline appearing in 2022 and 2023.) This landmark step forward was made possible by the breakthrough discovery of a test — validated in April 2023 by The Michael J. Fox Foundation's Parkinson's Progression Markers Initiative — capable of detecting the earliest believed pathology of PD even prior to the onset of any visible symptoms. The test, known as the alpha-synuclein seed amplification assay (aSyn-SAA), detects dysfunctional alpha-synuclein protein, one of the two biological hallmarks of PD alongside dopaminergic transport dysfunction, which can be visualized later in the disease process in the brain using DaTScan. Together, these two hallmarks serve as the basis for the NSD-ISS staging system. Key details include:
Because the framework encompasses clinical syndromes for which dysfunctional asyn is the defining biological hallmark, it applies to — and stands to improve treatment for — both PD and dementia with Lewy Bodies (DLB). The NSD-ISS unifies PD and DLB along the same continuum of progression based on a standardized biological diagnosis. Framework Developed through Open Multistakeholder Collaboration "Inviting scientific discourse from a multitude of perspectives is a key principle and a shared value of every organization and individual in the working group effort," said Sohini Chowdhury, The Michael J. Fox Foundation's chief program officer and a coauthor on the paper. "This new research framework is the product of a diverse community of contributors, whose inputs have helped to align and harmonize this first meaningful step toward a shared tool for researchers and the biopharma industry." NSD-ISS Will Become a Research Accelerator for the Field
"Our shared hope is that this new framework will foster innovation in clinical development, making trials more efficient and streamlining regulatory review. In short, the NSD-ISS is a research accelerator. And it is expected to evolve with accumulating scientific knowledge," said Tanya Simuni, MD, lead author on the paper, professor of neurology and director of the Parkinson's Disease Movement Disorders Center at Northwestern University. "The success that the Alzheimer's field has had with its biological framework provides the inspiration and motivation to achieve similar accelerated timelines in Parkinson's. Ten years from now, we hope we will look back and say this framework was the key that finally opened the door to next-generation treatments in Parkinson's." As Simuni and her coauthors note in The Lancet Neurology paper, the framework offers an actionable proposal to researchers and industry creating a new path for efficient clinical trials, but at present, it is not intended for use in routine clinical care. The paper includes acknowledgement that data supporting concepts of the NSD-ISS framework have emerged largely from the Foundation's landmark PPMI study. Major funding for PPMI comes from Aligning Science Across Parkinson's (ASAP) (www.parkinsonsroadmap.org), a coordinated research initiative focused on accelerating the pace of discovery and informing the path to a cure for PD. ASAP support is enabling a seismic expansion of PPMI to increase recruitment efforts and remote testing for those at-risk for PD as well as expanding assay development efforts to enable breakthroughs such as the alpha-synuclein seed amplification assay. PPMI is additionally funded by a consortium of more than 40 biotech and pharmaceutical firms providing financial and in-kind support, and by tens of thousands of individual donors to The Michael J. Fox Foundation. Heralded as "the study that's changing everything" about how Parkinson's is diagnosed, managed and treated, PPMI and its data are made possible by the more than 2,000 in-clinic and 40,000 online research volunteers with and without Parkinson's disease. "It's still early, but this framework will have an immediate impact in terms of how we're designing clinical protocols and optimizing research that can lead to better treatments that patients are waiting for," said Peter DiBiaso, MHSA, a coauthor on the paper, a drug development professional, and member of MJFF's Patient Council who was diagnosed with PD at 49. "We know there's a lot of work to be done, but this is the most important first step the field can take together to rapidly advance breakthroughs for patients and families." About The Michael J. Fox Foundation for Parkinson's Research (MJFF) View original content:https://www.prnewswire.co.uk/news-releases/patient-research-and-industry-leaders-propose-biological-definition-and-first-biological-staging-for-parkinsons-disease-302041449.html |