Human Umbilical Cord-Derived Mesenchymal Stem Cells in the Treatment of Multiple Sclerosis Patients: Phase I/II Dose-Finding Clinical Study.

Multiple sclerosis (MS) is a chronic neuro-inflammatory disease resulting in disabilities that negatively impact patients' life quality. While current treatment options do not reverse the course of the disease, treatment using mesenchymal stromal/stem cells (MSC) is promising. There has yet to be a consensus on the type and dose of MSC to be used in MS. This work aims to study the safety and efficacy of two treatment protocols of MSCs derived from the umbilical cord (UC-MSCs) and their secretome. The study included two groups of MS patients; Group A received two intrathecal doses of UC-MSCs, and Group B received a single dose. Both groups received UC-MSCs conditioned media 3 months post-treatment. Adverse events in the form of a clinical checklist and extensive laboratory tests were performed. Whole transcriptome analysis was performed on patients' cells at baseline and post-treatment. Results showed that all patients tolerated the cellular therapy without serious adverse events. The general disability scale improved significantly in both groups at 6 months post-treatment. Examining specific aspects of the disease revealed more parameters that improved in Group A compared to Group B patients, including a significant increase in the (CD3+CD4+) expressing lymphocytes at 12 months post-treatment. In addition, better outcomes were noted regarding lesion load, cortical thickness, manual dexterity, and information processing speed. Both protocols impacted the transcriptome of treated participants with genes, transcription factors, and microRNAs (miRNAs) differentially expressed compared to baseline. Inflammation-related and antigen-presenting (HLA-B) genes were downregulated in both groups. In contrast, TNF-alpha, TAP-1, and miR142 were downregulated only in Group A. The data presented indicate that both protocols are safe. Furthermore, it suggests that administering two doses of stem cells can be more beneficial to MS patients. Larger multisite studies should be initiated to further examine similar or higher doses of MSCs.

The long-term effect of neurodynamics vs exercise therapy on pain and function in people with carpal tunnel syndrome: A randomized parallel-group clinical trial.

INTRODUCTION: Carpal tunnel syndrome (CTS) is a common disorder that limits function and quality of life. Little evidence is available on the long-term effect of neurodynamics and exercise therapy. PURPOSE OF THE STUDY: This study aimed to examine the long-term effect of neurodynamic techniques vs exercise therapy in managing patients with CTS. STUDY DESIGN: Parallel group randomized clinical trial. METHODS: Of 57 patients screened, 51 were randomly assigned to either receiving four sessions of neurodynamics and exercise or home exercise therapy alone as a control. Blinded assessment was performed before treatment allocation, at treatment completion, and 6 months posttreatment. Outcome measures included Symptom Severity Scale (SSS), Functional Status Scale (FSS), Shortened version of the Disabilities of the Arm, Shoulder, and Hand (DASH), Numerical Pain Rating Scale, grip strength and range of motion. RESULTS: Data from 41 individuals (52 hands) were analyzed. The neurodynamics group demonstrated significant improvement in all outcome measures at 1 and 6 months (P < .05). Mean difference in SSS was 1.4 (95% CI= 0.9-1.4) at 1 month and 1.6 (95% CI = 0.9-2.2) at 6 months. Mean difference in FSS was 0.9 (95% CI = 0.4-1.4) at 1 month and 1.4 (95% CI = 0.7-2.0) at 6 months. Significant between-group differences were found in pain score at 1 month (-1.93) and in FSS (-0.5) and Shortened version of DASH (-12.6) at 6 months (P < .05). No patient needed surgery 1 year after treatment. CONCLUSIONS: Although both treatments led to positive outcomes, neurodynamics therapy was superior in improving function and strength and in decreasing pain.

The effect of stem cell therapy and comprehensive physical therapy in motor and non-motor symptoms in patients with multiple sclerosis: A comparative study.

INTRODUCTION: People with multiple sclerosis (PwMS) experience a wide range of disabilities which negatively impact their quality of life (QOL). Several interventions have been used in PwMS such as medication, physical therapy exercises and stem cell therapy to improve their QOL. However, there is a limited evidence on the benefits of combining interventions. The purpose of this study is to explore the effect of combining physical therapy exercises (PTE) and Wharton Jelly mesenchymal stem cell (WJ-MSCs) injections on motor and non-motor symptoms versus each intervention alone in PwMS. METHODS: Sixty PwMS will be allocated to either PTE, WJ-MSCs, or a combined group, followed up for 12 months and examined using a comprehensive battery of measures. Participants in the PTE group will receive 2 sessions per week of a supervised exercise program for 6 months followed by a home exercise program for another 6 months. The WJ-MSCs group will receive 3 WJ-MSCs injections in the first 6 months then they will be encouraged to follow an active life style. The third group will receive both interventions. DISCUSSION: This study will aid in a better understanding of the combined effect of physical therapy and mesenchymal stem cell therapy. The results from this proposed study may reduce disability, improve QOL in PwMS, and consequently, reduce the cost associated with the life-time care of these individuals worldwide. TRIAL REGISTRATION NUMBER: NCT03326505.