BACKGROUND: No treatments are currently available that slow, stop, or reverse 
disease progression in established multiple sclerosis (MS). The Mesenchymal Stem 
Cells in Multiple Sclerosis (MSCIMS) trial tests the safety and feasibility of 
treatment with a candidate cell-based therapy, and will inform the wider 
challenge of designing early phase clinical trials to evaluate putative 
neuroprotective therapies in progressive MS. Illustrated by the MSCIMS trial 
protocol, we describe a novel methodology based on detailed assessment of the 
anterior visual pathway as a model of wider disease processes--the "sentinel 
lesion approach".
METHODS/DESIGN: MSCIMS is a phase IIA study of autologous mesenchymal stem cells 
(MSCs) in secondary progressive MS. A pre-test : post-test design is used with 
healthy controls providing normative data for inter-session variability. 
Complementary eligibility criteria and outcomes are used to select participants 
with disease affecting the anterior visual pathway.
RESULTS: Ten participants with MS and eight healthy controls were recruited 
between October 2008 and March 2009. Mesenchymal stem cells were successfully 
isolated, expanded and characterised in vitro for all participants in the 
treatment arm.
CONCLUSIONS: In addition to determining the safety and feasibility of the 
intervention and informing design of future studies to address efficacy, MSCIMS 
adopts a novel strategy for testing neuroprotective agents in MS--the sentinel 
lesion approach--serving as proof of principle for its future wider 
applicability.
TRIAL REGISTRATION: ClinicalTrials.gov (NCT00395200).