Being able to correctly monitor the level of MS activity is always important in clinical care, but particularly so during a clinical drug trial where the ability of a new drug to stop MS activity is being assessed. Currently, monitoring progression of MS over time in clinical trials is challenging and there is no one test which can accurately make that assessment.
We currently know that as MS progresses, inflammatory cells within the brain called microglia are active, and likely to be contributing to disease progression over time. However, there are different types of microglia, pathogenic (indicating active disease) and reparative (indicating a repairing phase and less disease activity). At present, there is no way to distinguish between the two types of microglia to measure the microglial response and to know if MS progression is occurring.
Dr Vivash and her team aim to develop techniques to identify both the extent and the nature of this microglial response. They plan on doing this by developing a new compound to be used in a non-invasive PET (positron emission tomography) scan to determine the level of disease activity and MS progression. This could help fill an unmet need in clinical trials for new MS drugs by helping to identify effective drugs to treat progressive MS sooner and more accurately.
Using medicinal chemistry, the team have successfully identified three potent compounds for potential use in PET imaging. Two of these compounds have been selected for further analysis, which involved measuring their ability to cross the blood brain barrier (BBB). This analysis revealed that the two compounds can penetrate the central nervous system (CNS) and can freely move across the BBB, as well as maintain excellent blood and brain concentrations. Additionally, laboratory work has predicted that these two compounds have low non-specific binding to tissue. This work indicates that these compounds have met all the critical parameters needed for use in PET imaging.
The team will next conduct PET imaging in laboratory models to test out the new compounds.
This work has been published in a scientific journal and the team is in the process of submitting another manuscript for publication.
Wong SW, Vivash L, Mudududdla R, Nguyen N, Hermans SJ, Shackleford DM, Field J, Xue L, Aprico A, Hancock NC, Haskali M, Stashko MA, Frye SV, Wang X, Binder MD, Ackermann U, Parker MW, Kilpatrick TJ, Baell JB. Development of [18F]MIPS15692, a radiotracer with in vitro proof-of-concept for the imaging of MER tyrosine kinase (MERTK) in neuroinflammatory disease. Eur J Med Chem. 2021 Dec 15;226:113822. doi: 10.1016/j.ejmech.2021.113822. Epub 2021 Sep 4. PMID: 34563964.
Updated 31 March 2022
Updated: 19 January, 2021
Laboratory research that investigates scientific theories behind the possible causes, disease progression, ways to diagnose and better treat MS.
Research that builds on fundamental scientific research to develop new therapies, medical procedures or diagnostics and advances it closer to the clinic.
Clinical research is the culmination of fundamental and translational research turning those research discoveries into treatments and interventions for people with MS.