Evaluation of neurotrophic factor secreting mesenchymal stem cells in progressive multiple sclerosis
Jeffrey A. Cohen, Fred Lublin, Christopher Lock, Daniel Pelletier, Tanuja Chitnis, Munish Mehra, Yaël Gothelf, Revital Aricha, Stacy Lindborg, Chaim Lebovits, Yossef S. Levy, Afsaneh Motamed Khorasani, R. Kern
Abstract
BACKGROUND: ) have the potential to modify underlying disease mechanisms in progressive multiple sclerosis (PMS). OBJECTIVE: This open-label phase II study was conducted to evaluate safety/efficacy of three intrathecal cell treatments. METHODS: Eighteen participants with non-relapsing PMS were treated. The primary endpoint was safety. Secondary endpoints included: cerebrospinal fluid (CSF) biomarkers; timed 25-foot walk speed, nine-hole peg test (9-HPT), low-contrast letter acuity, symbol digit modalities test, and 12-item multiple sclerosis (MS) walking scale. Seventeen participants received all treatments. RESULTS: No deaths/adverse events related to worsening of MS, clinical/magnetic resonance imaging (MRI) evidence of disease activation, and clinically significant changes in safety lab results were reported. Two participants developed symptoms of low back and leg pain, consistent with a diagnosis of arachnoiditis, occurring in one of three intrathecal treatments in both participants. Nineteen percent of treated participants achieved pre-specified ⩾ 25% improvements in timed 25-foot walk speed/nine-HPT at 28 weeks compared to baseline, along with consistent efficacy signals for pre-specified response criteria across other secondary efficacy outcomes. CSF neuroprotective factors increased, and inflammatory biomarkers decreased after treatment, consistent with the proposed mechanism of action. CONCLUSION: Based on these encouraging preliminary findings, further confirmation in a randomized study is warranted.