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Interview with Dr. Susan Gauthier about her work on the MRI technique myelin-water fraction imaging for MS research - part 2

Gauthier & Vartanian MS AAN 2014 part 2

Interview by Dr. Timothy Vartanian, Director of the Judith Jaffe Multiple Sclerosis Center, with Dr. Susan Gauthier, Associate Professor in Neurology at the Weill Cornell Medical College (NY) and Director of Clinical Research at the Judith Jaffe Multiple Sclerosis Center.

Dr. Vartanian asks how Dr. Gauthier would design a clinical study with a seemingly potent myelin re-modelling drug. Such a study would not be done with patients with progressive MS, as one needs to have an intact axon to be able to remyelinate. It will include early patients, with new, active lesions, as they will be most likely to benefit from such a drug. The drug will most likely stimulated endogenous re-myelination, which is known to occur in early lesions, but it is unknown for how long this takes place. Current research is aimed at determining this window for remodeling, using serial imaging to determine when it starts and how long it lasts. These data allow a sample size calculation, to implement myelin-water fraction imaging into a phase II clinical study.

It is expected that patients will have different levels of re-myelination in lesions, as there is a vast phenotype difference in the disease. This is exactly that our technique will allow us to study in more detail.

The goals of the PET project looking at early rrMS patients are two-fold: i) how the dynamics of activated microglia relates to lesion recovery, and ii) are there activated microglia beyond the lesions and could this lead to more degeneration outside of the lesions. In progressive patients microglia are believed to have a strong role in neurotoxicity and a more widespread appearance of active microglia is expected. PET is suited for this, as it is very specific – it is molecular targeting. For our microglia studies we use the ligand PK1-1195 that binds TSPO, which is expressed on mitochondria in activated microglia and macrophages. The safe radioactive ligand (labeled with C11, which is short-lived) is injected and travels to the brain where it binds to the cells. The radioactivity is measured. The big challenge with PET is to quantify the uptake of radioactivity by the microglia, for which we have now developed non-invasive quantitative methods. We are currently in the process of looking at our data using these novel methods. Early data show that we see diffuse activation of microglia and this can be reduced with anti-inflammatory drugs. Especially differences between patient groups will be of interest in further studies.