Targeting phosphocreatine metabolism in relapsing–remitting multiple sclerosis: evaluation with brain MRI, 1H and 31P MRS, and clinical and cognitive testing
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Fluoxetine and prucalopride might change phosphocreatine (PCr) levels via the cAMP–PKA pathway, an interesting target in the neurodegenerative mechanisms of MS.
We conducted a two-center double-blind, placebo-controlled, randomized trial including 48 relapsing–remitting MS patients. Patients were randomized to receive placebo (n = 13), fluoxetine (n = 15), or prucalopride (n = 14) for 6 weeks. Proton (1H) and phosphorus (31P) magnetic resonance spectroscopy (MRS) as well as volumetric and perfusion MR imaging were performed at weeks 0, 2, and 6. Clinical and cognitive testing were evaluated at weeks 0 and 6.
No significant changes were observed for both 31P and 1H MRS indices. We found a significant effect on white matter volume and a trend towards an increase in grey matter and whole brain volume in the fluoxetine group at week 2; however, these effects were not sustained at week 6 for white matter and whole brain volume. Fluoxetine and prucalopride showed a positive effect on 9-HPT, depression, and fatigue scores.
Both fluoxetine and prucalopride had a symptomatic effect on upper limb function, fatigue, and depression, but this should be interpreted with caution. No effect of treatment was found on 31P and 1H MRS parameters, suggesting that these molecules do not influence the PCr metabolism.
KeywordsMultiple sclerosis Fluoxetine Prucalopride Magnetic resonance spectroscopy Phosphocreatine
We would like to thank our study nurses Karolien Flamée and Reinhilde Goorts for all the help with data input. We would like to thank everyone at icometrix, especially Diana Sima and Thibo Billiet for all their support with the analysis of the data.
We received funding of the MS Liga Belgium, MS steunfonds Vlaanderen. MC has a PhD fellowship funded by the FWO (Fonds Wetenschappelijk Onderzoek).
Compliance with ethical standards
Conflicts of interest
The authors declare that there is no conflict of interest.
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