Multiple Sclerosis Journal - October 2017 - 1477

G Datta, IR Violante et al.
independent predictive value for future neurodegeneration and disability change.
This small study was powered to test for a relatively
strong, general relationship between [myo-inositol]
and PET [11C]PBR28 uptake in MS. While the results
distinguish between results from the two measures, a
limitation of the study design is that a broad range
of disease was investigated with a relatively small
sample size. The possibility of a relationship under
some specific conditions cannot be ruled out. If
increased TSPO expression and radioligand binding
depends on the specific activation phenotypes of
astrocytes, the conclusion that PET TSPO radioligand
uptake reflects microglial activation predominantly
could not be generalised safely. This deserves further
histopathological study. However, post-mortem studies in MS consistently show that TSPO expression
does not appear to be significant in astrocytes.8,12
A fundamental limitation lies in the use of the MRS
[myo-inositol] as an index of astrogliosis. While there
is a strong evidence in support of the approach from
correlative neuropathology,4 anabolic and catabolic
pathways for myo-inositol are expressed in other cell
types, as well.5 Additional corroborative observations
with other, potential more specific markers of astrocyte activation would support the argument.35
Acknowledgements
The authors thank Dr Maria Davy of GlaxoSmithKline
(GSK) for constructive comments on the study design
and its early progression and gratefully acknowledge
support from the Imperial College Healthcare Trust
Biomedical Research Centre.
Declaration of Conflicting Interests
The author(s) declared the following potential conflicts of interest with respect to the research, authorship and/or publication of this article: G.D. is an
Imperial Wellcome-GSK Trust Training Fellow in
Translational Medicine and Therapeutics and thanks
GlaxoSmithKline for personal support in this context.
P.M.M. is in receipt of generous personal and research
support from the Edmond J Safra Foundation and Lily
Safra, the Medical Research Council, the Progressive
MS Alliance and the UK Engineering and Physics
Science Research Council for aspects of this work.
P.M.M. acknowledges consultancy fees (paid to his
institution) from Roche, Transparency Life Sciences,
IXICO, Adelphi Communications and OrbiMed. He
has received honoraria or speakers' fees (also paid to
his institution) from Novartis and Biogen and has
received research or educational funds from Biogen,
Novartis and GlaxoSmithKline.
journals.sagepub.com/home/msj

Funding
The author(s) disclosed receipt of the following financial support for the research, authorship and/or publication of this article: This work was supported, in
part, by GSK as part of the Imperial Wellcome-GSK
Trust Training Fellowship in Translational Medicine
and Therapeutics.

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