Mesenchymal Stem Cells in Multiple Sclerosis (MSCIMS) (MSCIMS)

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) 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 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: Primary Adverse events 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 Tertiary Multiple Sclerosis Functional Composite Score Expanded Kurtzke Disability Status Score

Multiple Sclerosis, Safety, Therapeutics, Mesenchymal Stem Cells, Multipotent Mesenchymal Stromal Cells, Optic Neuritis

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

Connick P, Kolappan M, Patani R, Scott MA, Crawley C, He XL, Richardson K, Barber K, Webber DJ, Wheeler-Kingshott CA, Tozer DJ, Samson RS, Thomas DL, Du MQ, Luan SL, Michell AW, Altmann DR, Thompson AJ, Miller DH, Compston A, Chandran S. The mesenchymal stem cells in multiple sclerosis (MSCIMS) trial protocol and baseline cohort characteristics: an open-label pre-test: post-test study with blinded outcome assessments. Trials. 2011 Mar 2;12:62. doi: 10.1186/1745-6215-12-62.

Connick P, Kolappan M, Crawley C, Webber DJ, Patani R, Michell AW, Du MQ, Luan SL, Altmann DR, Thompson AJ, Compston A, Scott MA, Miller DH, Chandran S. Autologous mesenchymal stem cells for the treatment of secondary progressive multiple sclerosis: an open-label phase 2a proof-of-concept study. Lancet Neurol. 2012 Feb;11(2):150-6. doi: 10.1016/S1474-4422(11)70305-2. Epub 2012 Jan 10.