Awarded by Aligning Science Across Parkinson’s (ASAP), in partnership with The Michael J. Fox Foundation for Parkinson’s Research (MJFF), the two grants of $9 million each will support research aimed at addressing key gaps in understanding the development and progression of Parkinson’s disease.
Parkinson’s disease (PD) is one of the fastest growing neurological disorders in the world, yet there are no treatments that can slow or cure the condition. The CRN brings together leading researchers around the world with the aim of mapping the biological blueprint of Parkinson’s disease and building a standardised toolkit of global research resources to help turn discoveries into treatments.
This next phase of the CRN initiative focuses on understanding why Parkinson’s disease varies across individuals, and advancing discoveries toward more precise diagnostics and therapies for patients.
About the projects:
Andrew Sharott
Professor Andrew Sharott, who is Associate Director of the MRC CoRE in Restorative Neural Dynamics, will be the Lead-Investigator on a team examining whether different sleep problems in Parkinson’s are caused by specific disruptions to distinct brain oscillations. Working in collaboration with Dr Angelina Maric and Dr Daniela Noain ( University of Zurich) Professor Derk -Jan Dijk (University of Surrey) and Professor Aleksandar Videnovic (Massachusetts General Hospital/Harvard University), the team will test whether restoring these activities to their healthy state will improve these specific aspects of sleep and slow down the progression of nerve cell loss.
People affected by Parkinson’s experience a range of sleep problems such as excessive daytime sleeping and difficulty sleeping at night. In a healthy brain, the different stages of sleep and wakefulness are carefully coordinated by oscillatory activity that synchronises nerve cells across the brain (brain oscillations). Whilst we know that this precise coordination is disrupted in Parkinson’s, we don’t know exactly how this causes specific sleep problems.
Using non-invasive approaches the team will record electrical activity from the brains of people with Parkinson’s to establish how brain oscillations in sleep relate to clinical symptoms. They will use rodent models of Parkinson’s to identify changes in the activity of large populations of nerve cells that cause these changes in patients. The researchers then aim to restore brain activities associated with sleep disturbance to normal levels using closed-loop modulation- - stimulating the brain with sound or electricity at specific times in relation to ongoing brain oscillations to make them stronger or weaker. This will allow them to quantify the effects of this stimulation in terms of changes in symptoms in people with Parkinson’s, and on neurodegeneration in the rodent models.
Professor Sharott says “Sleep disturbances have a significant, yet often overlooked, effect on the quality of life of people with Parkinson’s disease. In addition, many investigators think that poor quality of sleep could accelerate the disease process. This project will provide a fantastic opportunity to define the neural mechanisms underlying different sleep disturbances and to utilise this knowledge to develop novel, scalable therapeutics that may help address sleep disturbances in people with Parkinson’s disease”
Laura Parkkinen
Professor Laura Parkkinen, Professor of Translational Neuropathology and Director of the Oxford Brain Bank, who is also a Group Leader at the new UK DRI Parkinson’s disease Centre, will serve as a Co-Investigator on a team examining the role of a-synuclein and protein misfolding in the development and progression of Parkinson’s disease. Working in collaboration with Professors Matthias Mann (Max Planck Institute of Biochemistry) and Günter Höglinger and Franziska Hopfner (LMU University Hospital), the team aims to understand why Parkinson's progresses so differently between patients despite shared clinical and pathological features.
This variability is further complicated by the fact that around one in three people with Parkinson’s also develops additional brain pathologies, such as Alzheimer’s disease or vascular dementia, which can accelerate decline and make diagnosis and treatment more challenging. The researchers will focus on identifying the molecular factors that influence how α-synuclein, a protein that aggregates in the brains of people with Parkinson's, spreads and causes damage. To do this, the team will analyse samples from brain tissue, cerebrospinal fluid, blood, and skin to determine what drives protein aggregation.
The Parkkinen lab in Oxford has pioneered work in human neuropathology, with particular expertise in the molecular mechanisms underlying α-synuclein seeding and its role in neurodegeneration in Parkinson’s disease.
Professor Parkkinen says “Every Parkinson’s patient is different—their symptoms, their rate of decline, their response to treatment. We want to understand why. By analysing the full spectrum of proteins in patient samples, and how these relate to α-synuclein seeding activity, we can begin to uncover the distinct molecular patterns behind each person’s disease. That is the foundation for earlier diagnosis, better monitoring, and treatments that target the underlying causes rather than just the symptoms.”
Read the full announcement from ASAP: https://parkinsonsroadmap.org/news/261m-investment-toward-personalized-treatments/