• Visual function (acuity and colour) [ Time Frame: 12 and 52 weeks post treatment ] [ Designated as safety issue: No ]
• Visual evoked potential latency [ Time Frame: 12 and 52 weeks post treatment ] [ Designated as safety issue: No ]
• Optic nerve Magnetisation Transfer Ratio [ Time Frame: 12 and 52 weeks post treatment ] [ Designated as safety issue: No ]
• Retinal nerve fibre layer thickness (by optical coherence tomography) [ Time Frame: 12 and 52 weeks post treatment ] [ Designated as safety issue: No ]
• Brain lesion Magnetisation Transfer Ratio [ Time Frame: 12 and 52 weeks post treatment ] [ Designated as safety issue: No ]
• MRI brain T1 hypointensity load [ Time Frame: 12 and 52 weeks post treatment ] [ Designated as safety issue: No ]
• Multiple Sclerosis Functional Composite Score [ Time Frame: 12 and 52 weeks post treatment ] [ Designated as safety issue: No ]
• Expanded Kurtzke Disability Status Score [ Time Frame: 12 and 52 weeks post treatment ] [ Designated as safety issue: No ]

• Visual function (acuity and colour)
• Visual evoked potential latency
• Optic nerve Magnetisation Transfer Ratio
• Retinal nerve fibre layer thickness (by optical coherence tomography)
• Brain lesion Magnetisation Transfer Ratio
• MRI brain T1 hypointensity load
• T cell response suppression
• Multiple Sclerosis Functional Composite Score
• Expanded Kurtzke Disability Status Score

Hypothesis: Intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells is a safe novel therapeutic approach for patients with multiple sclerosis.

Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) is a phase I/IIA trial designed to establish the safety of intravenous administration of bone marrow-derived autologous adult human mesenchymal stem cells to patients with multiple sclerosis.

Disease under investigation: Multiple Sclerosis

Phase: I/IIA

Number of patients: 10

Design: 18 month cross over, single treatment at 6 months

Intervention: Administration of bone marrow-derived autologous mesenchymal stem cells

Route of administration: Intravenous

Dose: Up to 2,000,000 Mesenchymal Stem Cells per kilogram

Source of patients: Referrals accepted from Neurologists in East Anglia and North London, UK

Referral Criteria: (all 3 required)

1. Clinically definite multiple sclerosis
2. Expanded Kurtzke Disability Status Score 2.0 - 6.5 (inclusive)

3. Evidence of optic nerve damage by

   • history of optic neuritis, or
   • relative afferent pupillary defect, or
   • optic atrophy on fundoscopy, or
   • abnormal visual evoked potential from either or both eyes suggestive of demyelination

Primary Objective: Establish the safety of intravenously administered bone marrow-derived autologous mesenchymal stem cells at a dose of up to 2,000,000 cells/kg over 12 months by monitoring adverse reactions.

Secondary Objectives: Explore the efficacy of intravenously administered bone marrow-derived autologous mesenchymal stem cells at a dose of up to 2,000,000 cells/kg over 12 months on visual function by clinical, neurophysiological, and imaging assessments.

Outcome Measures:

1. Primary

   • Adverse events

2. Secondary

   • Visual function (acuity and colour)
   • Visual evoked potential latency
   • Optic nerve Magnetisation Transfer Ratio
   • Retinal nerve fibre layer thickness (by optical coherence tomography)
   • Brain lesion Magnetisation Transfer Ratio
   • MRI brain T1 hypointensity load
   • T cell response suppression

3. Tertiary

   • Multiple Sclerosis Functional Composite Score
   • Expanded Kurtzke Disability Status Score

Inclusion Criteria:

• Clinically definite multiple sclerosis
• Expanded Kurtzke Disability Status Score 2.0 - 6.5 (inclusive)
• Evidence of optic nerve damage by:
• history of optic neuritis, or
• relative afferent pupillary defect, or
• optic atrophy on fundoscopy, or
• abnormal visual evoked potential from either or both eyes suggestive of demyelination
• Prolonged visual evoked potential P100 latency with preserved waveform
• T2 lesion on MRI optic nerve
• Retinal nerve fibre layer thickness on optical coherence tomography > 40 microns

Exclusion Criteria:

• Age < 18 years
• Age > 65 years
• Patient lacks capacity to give informed consent
• Presence of a severe bleeding disorder
• Planning a pregnancy during the trial period
• Current MS disease modifying therapy

• Cambridge University Hospitals NHS Foundation Trust
• Medical Research Council