Feasibility Study of Tolerogenic Fibroblasts in Patients With Refractory Multiple Sclerosis
Condition: Multiple Sclerosis, Relapsing-Remitting; Multiple Sclerosis
MeSH terms: Multiple Sclerosis; Multiple Sclerosis, Relapsing-Remitting; Sclerosis
Study type: Interventional
Phase: Early Phase 1

Summary: 
      Fibroblasts have demonstrated potent immune modulatory and therapeutic activity in the
      experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, as well as in
      other models of autoimmune and inflammatory diseases.

      This study will assess primary safety and secondary efficacy endpoints of intravenous
      administration of 100 million tolerogenic fibroblasts to 5 patients with relapsing remitting
      MS resistant to interferon. While the safety of fibroblasts administered clinically is
      established, it is unknown whether these cells are effective in the treatment of multiple
      sclerosis (MS).

      Our hypothesis is that the tolerogenic fibroblasts will be well-tolerated and meet our
      primary objective. In addition, The investigators are optimistic that they will see signs of
      efficacy based on the following: Neurological assessment of the MS functional composite
      assessment which comprises of EDSS, the expanded EDSS (Rating Neurologic Impairment in
      Multiple Sclerosis, the Scripps neurological rating scale (NRS), paced auditory serial
      addition test (PASAT), the nine-hole peg test, and 25-foot walking time, short-form 36
      (SF-36) quality of life questionnaire and gadolinium-enhanced MRI scans of the brain and
      cervical spinal cord.
    

Detailed description: 
      Fibroblasts have demonstrated potent immune modulatory and therapeutic activity in the
      experimental autoimmune encephalomyelitis (EAE) model of multiple sclerosis, as well as in
      other models of autoimmune and inflammatory diseases. Mechanistically, tolerogenic
      fibroblasts produce anti-inflammatory and immune modulatory factors, which appear to be
      therapeutic in the context of autoimmunity, including IL-10 and TGF-beta. Additionally,
      tolerogenic fibroblasts produce neurotrophic mediators that enhance myelin production and/or
      prevent neuronal apoptosis.

      This study will assess primary safety and secondary efficacy endpoints of intravenous
      administration of 100 million tolerogenic fibroblasts to 5 patients with relapsing remitting
      MS resistant to interferon. While the safety of fibroblasts administered clinically is
      established, it is unknown whether these cells are effective in the treatment of multiple
      sclerosis (MS).

      Research Hypothesis: Intravenous administration of 100 million tolerogenic fibroblasts will
      be well tolerated and induce a therapeutic effect in relapse remitting MS patients.

      Rationale: The family of Mesenchymal Stem Cells (MSCs) is immune-modulatory, and bone marrow
      MSCs (BM-MSCs) have induced therapeutic responses in patients with MS [1]. Tolerogenic
      fibroblasts possess superior immune modulatory activity compared to BM-MSCs and adipose MSCs.
      The investigators, therefore, seek to perform a five-patient trial to assess the safety and
      signs of efficacy of this cell population in MS patients resistant to interferon.

      The trial's primary objective is freedom from treatment-associated adverse events at 1, 2, 4,
      8, and 16 weeks post-treatment. The study's secondary objective will be efficacy as assessed
      at baseline, weeks 2, 4, 8, and 16. The results will be quantified based on the following:
      Neurological assessment of the MS functional composite assessment, which comprises of EDSS,
      the expanded EDSS (Rating Neurologic Impairment in Multiple Sclerosis, the Scripps
      neurological rating scale (NRS), paced auditory serial addition test (PASAT), the nine-hole
      peg test, and 25-foot walking time, short-form 36 (SF-36) quality of life questionnaire and
      gadolinium-enhanced MRI scans of the brain and cervical spinal cord.
    

Intervention name(s): Tolerogenic Fibroblasts
Intervention type(s): Biological
Intervention description(s): administrating single dose of 100 million tolerogenic fibroblasts via intravenous infusion
Intervention model: Single Group Assignment
Intervention model description: The proposed study will assess primary safety and secondary efficacy endpoints of allogeneic tolerogenic fibroblasts administered through Intravenous infusion at a single dose of 100 million cells to 5 patients with relapsing remitting MS resistant to interferon.
Masking: None (Open Label)
Primary purpose: Treatment
Keywords: MS; Cell Therapy; Fibroblasts; Fibrobiologics; Stem cells; regenerative medicine; tissue regeneration; Immune modulation