Platelets are blood cells that play a key role in clot formation. Platelets also play a role in inflammation and can be used as markers of inflammation. This project aim to generate ‘proof of concept’ data that platelets are involved in the early stages of MS and using a novel contrast agent that targets activated platelets, diagnose early stages of MS. The team has generated novel imaging agents, specifically targeted to activated platelets for use with imaging technologies such as magnetic resonance imaging (MRI) and positron emission tomography (PET). Pilot data also indicates that these platelet-targeted imaging agents might be useful to image MS.
Professor Peter will first confirm the presence of activated platelets in early stages of MS (before the occurrence of symptoms) in a laboratory model of MS. They will then image the mouse brains after disease has been induced, to track inflammatory reactions that contribute to MS lesion development. PET imaging will be used as a sensitive clinically available method to systematically evaluate whether the newly generated imaging agents allow an early diagnosis of MS.
An early diagnosis of MS may allow treatments to be started earlier in the disease process and hopefully limit the development of lesions and their consequences.
Professor Peter and his team have achieved success in creating a novel nanoparticle-based imaging agent, specific to activated platelets. This agent is able to successfully target platelet-rich blood clots. Importantly, pilot data suggests that these imaging agents might be useful for imaging people with MS.
This project has confirmed clear differences in platelet levels in brain sections of mice with MS-like disease, compared to healthy mice, indicating a potential role for platelets in early MS. More importantly, platelet presence was seen in the brains of these mice before the onset of observable clinical symptoms or brain lesions, supporting the idea of using them as diagnostic targets in early MS. Higher platelet levels were also associated with reduced levels of a structural filament that supports nerve cells, suggesting platelets may play an important role in the brain pathology associated with MS. In addition, preliminary experiments have demonstrated that mice with platelet depletion also show delayed onset of symptoms.
The next stage of the research has attempted to track the activated platelets within the animal models at the early stage of MS. Using novel imaging probe technologies applied to positron emission tomography / computerised tomography (PET/CT), this work demonstrated higher levels of platelets in MS-like mice, compared to healthy mice. This important work suggests that PET/CT imaging could be used for imaging the early stages of MS.
The final study undertaken in this project has aimed to test the relationship between platelets and the brain lesions observed in MS. In continuation of the microscopy study reported above, where platelets were found in the brains of mice with MS-like disease, further analyses revealed that the platelets were located in close proximity to brain lesions, and were correlated with the presence of microglial cells, the immune cells of the brain, whose presence is a hallmark of illness in MS-like mice. These findings were then confirmed using histological staining of the post-mortem mouse brains.
This important project has very promising implications for the future identification and early diagnosis of MS. Additional research is needed to understand the pathological role of platelets in humans with MS, to develop imaging technologies for early diagnosis of MS, and explore potential therapeutic targets by reducing or inhibiting platelets in humans.
This research is also being supported via an MS Research Australia PhD Scholarship awarded to Mr. Ashish Nair.
Updated: 30 June 2014
Updated: 03 January, 2013