RNA dysregulation likely contributes to disease pathogenesis of amyotrophic lateral sclerosis (ALS) and other neurodegenerative diseases. A pathological form of the transactive response (TAR) DNA binding protein (TDP-43) binds to RNA in stress granules and forms membraneless, amyloid-like TDP-43 aggregates in the cytoplasm of ALS motor neurons. In this study, we hypothesized that by targeting the RNA recognition motif (RRM) domains of TDP-43 that confer a pathogenic interaction between TDP-43 and RNA, motor neuron toxicity could be reduced. In silico docking of 50000 compounds to the RRM domains of TDP-43 identified a small molecule (rTRD01) that (i) bound to TDP-43's RRM1 and RRM2 domains, (ii) partially disrupted TDP-43's interaction with the hexanucleotide RNA repeat of the disease-linked c9orf 72 gene, but not with (UG) 6 canonical binding sequence of TDP-43, and (iii) improved larval turning, an assay *

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease with a heterogeneous course that ultimately leads to death. Currently, there is no cure, and new treatments that can slow the progression of the disease are needed. Stem cell (SC) transplantation is an emerging therapy that has shown a lot of potential in recent clinical trials. This review is aimed to examine the results of various clinical trials on this topic, thus assessing the safety and efficacy of SC transplantation as a potential treatment for ALS. We identified 748 studies in our search, of which 134 full-text studies were assessed for eligibility. Six studies met the inclusion criteria and were included in this review. Although some of the included studies showed the positive effect of SC transplantation, other studies found that there was no significant difference compared to the control group. We observed more positive effects with bone marrow mesenchymal stem cells (BM-MSC) treatments than Granulocyte colony-stimulating factor (G-CSF) ones. However, other factors, such as route of administration, number of doses, and number of cells per dose, could also play a role in this discrepancy. Based on this information, we conclude that more properly conducted clinical trials are needed to appreciate the benefit of this treatment.

BackgroundObesity and its complications are associated with several adverse effects that may cause a serious impact on health. Antipsychotics-induced weight gain (AIWG) is one of the major, yet often neglected side effects of first and second generations antipsychotics. Importantly, several researches have shown metformin to be effective in managing weight gain especially, with AIWG. This study investigated the effect of antipsychotics use on weight gain and the theory of metformin concomitant use on the prevention of AIWG.MethodsA retrospective cohort review of the medical records of patients from the psychiatry outpatient clinics in the King Abdulaziz Medical city, a tertiary hospital in Jeddah from May 2016 to August 2021. The population of patients in Psychiatry section was 4,141. The sampling technique was a non-random consecutive sampling technique. Moreover, the included patients’ records were divided to group 1 (patients on antipsychotics) and group 2 (patients using antipsychotics with Metformin).ResultsAccording to the study criteria, 395 patients’ records were included. A total of 309 (78%) patients were using antipsychotics without metformin, which in this study were depicted as group 1. In addition, a total of 86 (22%) were using antipsychotics with metformin, which in this study were assigned as group 2. Out of Group 1 patients (n= 309), only 67 patients experienced weight loss (21.68%), 43 remained with no weight change (13.92%), and 199 experienced weight gain (64.4%). Out of Group 2 patients (n= 86), 35 patients experienced weight loss (40.7%), 18 patients remained with no weight change (20.93%), and 33 experienced weight gain (38.37%). In addition, group 1 had a mean weight change of 2.5 kg, whereas group 2 had a mean weight change of −0.04 kg.ConclusionStatistical analysis revealed that patients on antipsychotics alone experienced weight gain, whereas the concomitant use of metformin showed reduction in the weight gain tendency. Thus, study outcomes indicate that concomitant use of metformin with antipsychotics might significantly reduce the AIWG.