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.

Could vagus nerve stimulation influence bone remodeling?

OBJECTIVES: To investigate the effect of vagus nerve stimulation (VNS) on the bone mineral density (BMD) in epileptic patients. METHODS: A prospective cohort study was conducted on individuals with refractory seizures who underwent VNS surgery between January 2012 and December 2018. BMD was measured preoperatively and between 6 months and one year after surgery. RESULTS: Twenty-one patients (mean age (±SD)=23.6±12.3 years) were recruited for the implantation of a VNS device. The mean absolute increase in lumbar BMD in the 21 patients was 0.04±0.04 g/cm2 resulting in an overall percent increase from baseline of 4.7±6.1%. BMD increased by an amount ≥ the least significant change (LSC) for the lumbar spine in 13 patients (61.9%). The lumbar Z score also increased in these patients from -1.22±1.15 to -0.88±1.22, P=0.006). Pre and Post VNA femoral BMD was measured in only 11 patients and, of those 3 showed a significant increase in BMD, 1 a significant decrease and 7 no change. CONCLUSION: The implantation of a VNS was associated with an increase in lumbar BMD. This study could lead to a new application for VNS in the treatment of osteoporosis.

Mini-mental state examination (MMSE) scores in elderly Jordanian population.

Background: The Mini-Mental State Examination (MMSE) is a simple informative and validated screening test of cognitive functions. No data of MMSE scores has been published about elderly Jordanian population. Objective: To study the MMSE scores in the elderly Jordanian population (defined as age of 50 years or more). Methods: This was a cross sectional study. A 250 healthy elderly Jordanians were interviewed and tested for their MMSE score. Their scores were analyzed and the effect of age, gender, education, marital status, diabetes mellitus (DM), hypertension (HTN), smoking, dyslipidemia, heart disease (HD), and family history of dementia (FHD) on the score was studied. Results: MMSE scores of 236 elderly subjects, aged 63±8.4 years (range 50-86 years) were analyzed. There were 111 (47%) males. There was a direct correlation between MMSE score and education level. People with a higher education (college) had the highest scores in comparison with people who are illiterates or have a high school level. The score correlated negatively with age (Pearson correlation r = -0.23, p = 0.00). Other studied variables did not correlate with score on multivariate analysis. Conclusion: Jordanians ≥50 years old with no previous brain disease scored 26.7 ± 3.2. Education was the most important determining factor of this score. the score showed also a negative correlation with age. We suggest that in this population a cut off score of 24 for those with high education beyond high school and 21 for those with up to high school education and it is not appropriate for illiterate.

Mesenchymal stem cells and conditioned media in the treatment of multiple sclerosis patients: Clinical, ophthalmological and radiological assessments of safety and efficacy.

AIMS: This open-label prospective phase I/IIa clinical study used autologous bone marrow-derived mesenchymal stromal cells (BM-MSCs) followed by mesenchymal stromal cells conditioned media (MSC-CM) for the first time to treat multiple sclerosis (MS) patients. The primary goal was to assess the safety and feasibility and the secondary was efficacy. The correlation between the MSC-CM content and treatment outcome was investigated. METHODS: Ten MS patients who failed conventional therapy were enrolled. Adverse events were recorded to assess safety. The Expanded Disability Status Scale (EDSS) was the primary efficacy measurement, the secondary included clinical (25WFT, 9-PHT), cognitive (MMS), ophthalmology (OCT, VEP), and radiological (MRI lesion and volume) tests. The MSCs-CM concentration of 27 inflammatory biomarkers was investigated. RESULTS: The treatment protocol was well tolerated by patients. There was an overall trend of improvement in all the tests, except the lesion volume which increased significantly. A decrease of 4 and 3.5 points on the EDSS was achieved in two patients. We report a correlation between a decreased lesion number at baseline and higher IL-6, IL-8, and VEGF MSC-CM content. CONCLUSION: The used protocol was safe and feasible with possible efficacy. The addition of MSC-CM could be related to the magnitude of EDSS improvement observed.

Clinical characteristics and outcomes of patients with idiopathic inflammatory myopathies from Jordan 1996-2009.

To describe demographic characteristics, clinical features and outcome of Jordanian patients with idiopathic inflammatory myopathies (IIM), a retrospective chart review of all patients diagnosed with IIM at Jordan University Hospital between 1996 and 2009 was carried out. Thirty patients with IIM were identified. Female to male ratio was 1.7:1, with mean age at diagnosis 34.3 ± 9.2 (10-72) years with bimodal presentation at 21 and 49 years and a mean follow-up of 6.5 ± 5.7 years. Eleven patients had polymyositis (PM); 19 patients had dermatomyositis (DM); 1 patient had DM with malignancy; 2 patients had juvenile DM; and 2 patients had DM/PM with other rheumatologic diseases. Raynaud's phenomenon was present in 26% of patients, dysphagia in 40%, fever in 16%, arthralgia/arthritis in 26%, and dyspnea was present in 26% patients. Positive muscle biopsy and EMG were present in 81% and 92% of patients, respectively. Elevated serum creatinine kinase (CK), AST/ALT and LDH were found in 90%, 72%, and 88% of patients at presentation, respectively. Interstitial fibrosis identified on high-resolution computed tomography (HRCT) was found in 7/14 (50%) patients. Restrictive lung disease was present in 16/21 (76%), low diffusion capacity of lung of carbon monoxide (DLCO) in 10/17 (59%) and pulmonary hypertension in only 3/19 (16%) patients tested. Arab Jordanian patients with IIM showed very low prevalence of malignancy, lower mean age than previous reports, and similar other clinical, laboratory and serologic markers, and survival rate to previous reports. Of interest, we found that extra-muscular manifestations were mainly associated with dermatomyositis.

MRI documented acute myelitis in a patient with Vogt-Koyanagi-Harada syndrome: first report.

MRI findings in transverse myelitis complicating Vogt-Koyanagi-Harada (VKH) syndrome have not been documented before. Here, we present a case with acute myelitis complicating VKH syndrome and show the MRI findings.

Lipid profile in Jordanian patients with first ever ischemic stroke.

OBJECTIVE: To study the relationship between lipid profile, total cholesterol (TC), low density lipoprotein (LDL), high density lipoprotein (HDL), and triglycerides (TG) in Jordanian patients admitted with first ever ischemic stroke (IS) to a teaching hospital over a 3-year-period, and compared them to a control group. METHODS: A retrospective case control study of all patients with diagnosis of IS who were admitted to the Jordan University Hospital, Amman, Jordan from January 2004 to December 2006 and had a documented fasting lipid profile within 48 hours of their admission. They were compared to controls without IS. RESULTS: Ninety-eight patients with IS were studied and compared to 98 control subjects. Both patients and control groups were similar regarding age, gender distribution, prevalence of hypertension, diabetes mellitus, ischemic heart disease (IHD), and smoking. The lipid profile showed a significantly lower HDL level in IS patients compared to the control group. There were no significant differences between the patients and control regarding TC, LDL, or TG levels. Control group used statins more frequently than patients (28% versus 10%, p=0.002). Both groups had high prevalence of risk factors. CONCLUSION: Though this study is limited by its retrospective design, it suggests that IS patients have significantly lower levels of HDL.