The Aligning Science Across Parkinson's (ASAP) initiative has awarded $11 million (approximately 9.5 million euros) to a project coordinated by Dr. Miquel Vila, head of the Neurodegenerative Diseases research group at the Vall d'Hebron Research Institute (VHIR) and ICREA Professor. The study will deepen the knowledge of the causes and mechanisms of Parkinson's disease and investigate possible new therapies that could be applied at early stages of the disease process.

Age is the main risk factor for developing Parkinson's disease. With age, the brain, especially the substantia nigra, accumulates a pigment known as neuromelanin. This pigment, which has similar characteristics to the melanin in the skin, can eventually occupy the entire neuron, giving the substantia nigra of the brain the dark brown appearance its name implies. In 2019, in a paper published in Nature Communications, Dr. Vila’s team showed that increased production of this pigment in animal models triggers degeneration in substantia nigra neurons and is linked to the development of parkinsonian features. "Now we want to analyze how this progressive accumulation of neuromelanin impairs neuronal function in different brain circuits affected in Parkinson’s disease," explains Dr. Vila, who is also a researcher at the Center for Networked Biomedical Research on Neurodegenerative Diseases (CIBERNED).

The project will focus not only on the substantia nigra, as the main region affected by the disease, but also on other melanized brain areas equally affected in Parkinson’s disease but rarely explored, such as the locus coeruleus. The role of neuromelanin in the dysfunction and degeneration of these brain circuits will be analyzed during the disease process, especially at preclinical or early stages of the disease. The project will also identify the mechanisms by which the disease progresses over time to other brain areas, and even outside of the brain, leading to non-motor symptoms that typically accompany the motor symptoms of the disease. These studies will be conducted in human brains as well as in experimental animal models in which the production of neuromelanin has been increased, as it occurs in Parkinson's patients, since most animal species do not naturally produce this brain pigment.

From a therapeutic point of view, the project will determine whether the reduction of neuromelanin levels or the modulation of brain circuit activity is able to restore the dysfunction that takes place in the affected brain. "Some of the potential therapeutic strategies that we propose to investigate in this project are non-invasive and safe for humans and could thus be directly transferred to patients if proven effective in experimental animals," says Dr. Vila.

This international multidisciplinary research project also involves researchers from CIBERNED, the University of Sydney, Tor Vergata University of Rome, and the Leibniz Institute for Neurobiology, as well as collaborators from the Karolinska Institute and the Achucarro Basque Center for Neuroscience.

Aligning Science Across Parkinson (ASAP)

Aligning Science Across Parkinson (ASAP) is a coordinated research initiative to advance targeted basic research for Parkinson’s disease. Its mission is to accelerate the pace of discovery and inform the path to a cure through collaboration, research-enabling resources, and data sharing. The Michael J. Fox Foundation for Parkinson’s Research is ASAP’s implementation partner and issued the grant.

“Each team selected for the ASAP Collaborative Research Network brings unique expertise and perspective to ASAP’s mission of tackling key knowledge gaps in disease understanding through open science. We are proud to partner with Vall d’Hebron on this innovative and impactful project that will position the field closer to new treatments for the millions living with and at risk of Parkinson’s disease,” says Dr. Ekemini Riley, ASAP Managing Director

More information can be found at: https://parkinsonsroadmap.org/