Safety, feasibility of intravenous and intrathecal injection of autologous bone marrow derived mesenchymal stromal cells in patients with amyotrophic lateral sclerosis: An open label phase I clinical trial

Objective: Amyotrophic lateral sclerosis [ALS] is the most severe disorder within the spectrum of motor neuron diseases [MND] that has no effective treatment and a progressively fatal outcome. We have conducted two clinical trials to assess the safety and feasibility of intravenous [IV] and intrathecal [IT] injections of bone marrow derived mesenchymal stromal cells [BM-MSCs] in patients with ALS

Materials and Methods: This is an interventional/experimental study. We enrolled 14 patients that met the following inclusion criteria: definitive diagnosis of sporadic ALS, ALS Functional Rating Scale [ALS-FRS] .24, and .40% predicted forced vital capacity [FVC]. All patients underwent bone marrow [BM] aspiration to obtain an adequate sample for cell isolation and culture. Patients in group 1 [n=6] received an IV and patients in group 2 [n=8] received an IT injection of the cell suspension. All patients in both groups were followed at 24 hours and 2, 4, 6, and 12 months after the injection with ALS-FRS, FVC, laboratory tests, check list of side effects and brain/spinal cord magnetic resonance imaging [MRI]. In each group, one patient was lost to follow up one month after cell injection and one patient from IV group died due to severe respiratory insufficiency and infection

Results: During the follow up there were no reports of adverse events in terms of clinical and laboratory assessments. In MRI, there was not any new abnormal finding. The ALS-FRS score and FVC percentage significantly reduced in all patients from both groups

Conclusion: This study has shown that IV and IT transplantation of BM-derived stromal cells is safe and feasible [Registration numbers: NCT01759797 and NCT01771640]

Heat shock protein 70 and the risk of multiple sclerosis in the iranian population

Multiple sclerosis [MS] is a chronic disease of the central nervous system and one of the most common causes of neurological disability among those aged 20-40 years, particularly in women. Major histocompatibility complex [MHC] Class II genes are known to be involved in the development of MS. One of the important groups of this complex is the HSP gene family, especially HSP70, which is induced under stress conditions. The aim of the present case-control study was to determine the association between the heat shock protein 70 [HSP70] and risk of MS in Iranian patients by genotyping the rs1061581 gene polymorphism. A total of 50 relapsing-remitting MS [RRMS] patients and 50 healthy control subjects were considered for this study. Genotyping was performed by the polymerase chain reaction-restriction fragment length polymorphism [PCRRFLP] method. PCR-RFLP results of twenty-five randomly selected samples were confirmed by DNA sequencing. Genotypic and allelic distributions were compared between the case and control groups. We observed no significant difference in the distribution of rs1061581 genotype and allele frequencies between RRMS patients and controls. In addition, there was no association between the HSP70 gene polymorphism and the clinical variables in the case group. Our data indicate that HSP70, in particular rs1061581, is unlikely to be involved in the susceptibility to or the severity of RRMS in Iranian patients. Further large prospective studies are required to confirm these findings

In silico perspectives on the prediction of the PLP's epitopes involved in multiple sclerosis

Background: Multiple sclerosis [MS] is the most common autoimmune disease of the central nervous system [CNS]. The main cause of the MS is yet to be revealed, but the most probable theory is based on the molecular mimicry that concludes some infections in the activation of T cells against brain auto-antigens that initiate the disease cascade

Objectives: The Purpose of this research is the prediction of the auto-antigen potency of the myelin proteolipid protein [PLP] in multiple sclerosis

Materials and Methods: As there wasn't any tertiary structure of PLP available in the Protein Data Bank [PDB] and in order to characterize the structural properties of the protein, we modeled this protein using prediction servers. Meta prediction method, as a new perspective in silico, was performed to find PLPs epitopes. For this purpose, several T cell epitope prediction web servers were used to predict PLPs epitopes against Human Leukocyte Antigens [HLA]. The overlap regions, as were predicted by most web servers were selected as immunogenic epitopes and were subjected to the BLASTP against microorganisms

Results: Three common regions, AA[58-74], AA[161-177], and AA[238-254] were detected as immunodominant regions through meta-prediction. Investigating peptides with more than 50% similarity to that of candidate epitope AA[58-74] in bacteria showed a similar peptide in bacteria [mainly consistent with that of clostridium and mycobacterium] and spike protein of Alphacoronavirus 1, Canine coronavirus, and Feline coronavirus. These results suggest that cross reaction of the immune system to PLP may have originated from a bacteria or viral infection, and therefore molecular mimicry might have an important role in the progression of MS

Conclusions: Through reliable and accurate prediction of the consensus epitopes, it is not necessary to synthesize all PLP fragments and examine their immunogenicity experimentally [in vitro]. In this study, the best encephalitogenic antigens were predicted based on bioinformatics tools that may provide reliable results for researches in a shorter time and at a lower cost

[Causes of absenteeism and lack of attention to the instructions among medical students of Islamic Azad University, Tehran Medical Branch]

Background: Learning is considered as the basis of the education system, and the other issues in this field depend on this important factor. The students' presence and their participation in the classroom are considered as the foundation for learning and education. This study was conducted to assess the causes of absenteeism and lack of attention to the instructions among medical students of Islamic Azad University, Tehran Medical Branch

Materials and methods: The participants of this causal- comparative study consisted of 375 students from basic medical science group. The instrument used for the present study was a 3- section form designed by the researcher himself

Results: Among the 4 factors affecting students' presence in the classroom, the instructors' performance was the major cause of their absenteeism and the next parameter was educational programming. Self and family problems and medical science situation in society were the other effective factors, respectively

Conclusion: According to our findings, the accurate and continuous assessment of the quality of instruction, holding methodology, expression skills, and successful interrelation skill workshops for the instructors especially the inexperienced, and modifying the educational programs will increase the students' interest to participate more in the classroom