• Adverse events
  

• 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
  

Disease under investigation: Multiple Sclerosis

Phase: I/IIA

Number of patients: 20

Design: 1 year cross over, single treatment at 6 months

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

Route of administration: Intravenous

Dose: 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 4 required)

1. Clinically definite multiple sclerosis
2. Disease duration 2 - 15 years
3. Expanded Kurtzke Disability Status Score 2.0 - 5.5 (inclusive)

4. Evidence of optic nerve damage by

   1. history of optic neuritis, or
   2. relative afferent pupillary defect, or
   3. optic atrophy on fundoscopy, or
   4. 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 2,000,000 cells/kg over 6 months by monitoring adverse reactions.

Secondary Objectives: Explore the efficacy of intravenously administered bone marrow-derived autologous mesenchymal stem cells at a dose of 2,000,000 cells/kg over 6 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
• Disease duration 2 - 15 years
• Expanded Kurtzke Disability Status Score 2.0 - 5.5
• 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
• <40% loss of retinal nerve fibre layer thickness on optical coherence tomography

Exclusion Criteria:

• Age < 18 years
• Age > 50 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