Download Endpoints for trials in Duchenne MD: Nuclear Magnetic Resonance

Endpoints for trials in Duchenne MD:
Nuclear Magnetic Resonance
Imaging and Spectroscopy
Thomas Voit
NIHR GOSH Biomedical Research Centre
Great Ormond Street Institute of Child Health
University College London
Muscle NMR can measure disease progression in DMD
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Muscle lipid quantification by MRS
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Senesac CR et al, 2015
Muscle NMR: correlation of lipids and function
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Senesac CR et al, 2015
One ‘stable’ DMD patient
Muscle NMR: cross-sectional study in DMD
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PLOS one, 2015
Muscle NMR: cross-sectional study in DMD
LOOKING AT INDIVIDUAL MUSCLES
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Vohra RS et al,
PLOS one 2015
Muscle NMR: longitudinal study in DMD
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Ann Neurol 2016
Muscle NMR: calculation of sample size
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Willcocks RJ, et al, 2016
Muscle NMR: effects of corticosteroids
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Neurology 2014
Muscle NMR: effects of corticosteroids
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Arpan I, et al, 2014
Muscle NMR: addressing the upper limbs
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Neurology 2016
PLOS one 2016
NMR in Biomedicine 2015
Muscle NMR: fatty transformation of upper arm muscles
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Ricotti V et al, 2016
Distal upper arm: correlation of NMR and muscle function
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Blue = ambulant, red = non-ambulant
Hogrel JY, et al, 2016
Upper limb
NMR spectroscopy
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Wary C, et al, 2015
Upper limb NMR spectroscopy:
Changes in ambulant and non-ambulant DMD
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Wary C et al, 2015
Spectroscopic abnormalities already
apparent at ambulant stage
Steep increase of fatty transformation
after loss of ambulation
Conclusions
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• NMR imaging and spectroscopy are increasingly used as
outcome measures for DMD
• Progressive fatty transformation but also other
parameters such as T2 or Phosphodiester over
Phosphocreatin can be quantified objectively
• MRI parameters show strong correlations with functional
measures
• Progressive changes can be detected when functional
measures are still improving
• Power calculations indicate that smaller trial cohorts are
necessary
Conclusions
• Different approaches, different mechanisms of
action
• Early-in-man studies, safety and proof-ofconcept
• Larger placebo-controlled data will have to be
obtained
• Individual windows of opportunity will have to
be defined
• In future: combinations may be synergistic (?)