Parkinson's disease (PD) is the leading disease affecting brain cells which results in movement disorders. It is characterized by the deposition of misfolded aggregates of a protein called alpha- synuclein within brain cells. These aggregates form clusters referred to as Lewy bodies and Lewy neurites within the affected cells. Autopsy results from patients with PD suggest that these protein aggregates start forming from the back of the brain and then spread to the center and other parts of the central nervous system. This process may last several years (can be decades), before patients start experiencing any movement disorders. Therefore, any technology which can detect the presence of these protein aggregates in living persons can be useful as an early detection tool for PD. To date, there is no such technology but there are several research efforts focused on developing a technique known as positron emission tomography (PET). This technology has been shown to work in imaging a similar type of misfolded protein aggregates called amyloid-beta plaques found in the brains of patients with Alzheimer's disease. However, PET agents are often limited to specialized medical centers and research labs, are cost prohibitive, and expose patients to hazardous radiation. There is a need for low cost and readily accessible imaging technologies for both clinical use and research purposes. We propose to develop a highly innovative approach to detect the presence of aggregates of alpha-synuclein in the brain using magnetic resonance imaging (MRI), which is less expensive and more accessible to both researchers and clinicians. The technology is based on a nanoparticle (bearing MRI-sensitive molecules), with the ability to selectively bind to alpha-synuclein aggregates. We hypothesize that when administered intravenously, these particles will cross from circulation into cerebrospinal fluid and bind to alpha-synuclein aggregates in the brain of a mouse model of Parkinson's disease, forming a complex. The resulting complex will then be taken up by brain and resident immune cells, allowing for accumulation of detectable levels of the MRI agent in affected regions of the brain. We intend to build on experience on developing a similar particle for imaging amyloid-beta plaques in mouse models of Alzheimer's disease (set to debut in clinical trials in early 2020), to carry this project to a successful completion.
Parkinson's disease is the most common neurodegenerative movement disorder. Its pathology is characterized by intracellular Lewy bodies and Lewy neurites composed primarily of aggregates of a misfolded protein called alpha-synuclein, which research has shown to begin forming in the brain, decades before clinical manifestation of the disease. Imaging these protein aggregates is thought to be a good approach to early detection of the disease, so we propose to develop a novel technology that can help detect their presence in the brain of a patient using MRI.
