Immunomodulation as a treatment for parkinson's disease in current trials: a systematic review and meta-analysis.

Background: Immunomodulatory drugs and immunotherapies are being evaluated in clinical trials for the treatment of neuroinflammation, as the latter is an essential mechanism for the development and progression of Parkinson's disease. Objective: The objective of the study is to review recent evidence on the evaluation of immunomodulators in randomized controlled clinical trials measuring improvement of motor symptoms. Methods: A meta-analysis of Movement Disorder Society-Unified Parkinson's disease Rating Scale (MDS-UPDRS III) scores extracted from seven articles selected after an online search of PubMed, Cochrane Library, and Clarivate's Web of Science for randomized controlled clinical trials published between 2000 and July 2023 was performed. The selected articles reported clinical trials evaluating the effects of specific immunomodulators or treatments with known effects on the immune system and inflammation. MDS-UPDRS III scores were reported in these studies, and the results of the placebo groups were compared with those of the treatment groups. Results: A total of 590 patients treated with immunomodulators and 622 patients treated with placebo were included. A test for heterogeneity yielded an I2 value > 50%. The mean standard difference for change in MDS-UPDR III score was -0.46 (CI [95%] = -0.90 - -0.02, p < 0.01). No significant differences were found in the change in mean MDS-UPDR III score between the treatment and placebo groups; however, two studies showed a trend toward separation from the mean. Conclusion: The immunomodulatory treatments included in this study showed no efficacy in improving motor symptoms in Parkinson's disease patients. Further clinical trials with larger patient populations are needed.

Meta-analysis to Implement Alpha-Synuclein in Extracellular Vesicles as a Potential Biomarker for Parkinsons Disease.

Background: In Parkinson's disease (PD), exosomes carry α-synuclein (α-syn), a fibrillar protein aggregates with potential value as a biomarker. Objective: Evidence on blood levels of exosomal α-syn in PD patients and controls was reviewed for their consistency. Methods: Thirty-six studies on exosomal α-syn concentrations in PD were identified in a systematic literature search and meta-analysis. Results: Both raw and ratio-adjusted blood exosomal α-syn levels were consistently higher in PD patients than in controls. The standardized mean difference (SMD) was 1.54 (0.18-2.90, CI95%, p < 0.01) and 1.53 (0.23-2.83, CI95%, p < 0.01), respectively. Conclusion: Our results suggest that exosomal α-syn concentrations could be a useful biomarker for PD.

Meta-analysis to Implement Alpha-Synuclein in Extracellular Vesicles as a Potential Biomarker for Parkinson's Disease

ABSTRACT Background: In Parkinson's disease (PD), exosomes carry α-synuclein (α-syn), a fibrillar protein aggregates with potential value as a biomarker. Objective: Evidence on blood levels of exosomal α-syn in PD patients and controls was reviewed for their consistency. Methods: Thirty-six studies on exosomal α-syn concentrations in PD were identified in a systematic literature search and meta-analysis. Results: Both raw and ratio-adjusted blood exosomal α-syn levels were consistently higher in PD patients than in controls. The standardized mean difference (SMD) was 1.54 (0.18-2.90, CI95%, p < 0.01) and 1.53 (0.23-2.83, CI95%, p < 0.01), respectively. Conclusion: Our results suggest that exosomal α-syn concentrations could be a useful biomarker for PD.

Characterization of excretory/secretory products of the Taenia crassiceps cysticercus involved in the induction of regulatory T cells in vivo.

The ability to modulate the host immune response has allowed some parasites to establish themselves in the tissues of an immunocompetent organism. While some parasite excretion/secretion products (ESPs) were recently reported to induce differentiation of regulatory T cells (Tregs), their identity is not known. This work is aimed to identify and characterize ESPs of Taenia crassiceps cysticerci linked with Treg induction in vivo. ESPs were obtained from cultures of T. crassiceps cysticerci and inoculated in mice, measuring Treg levels by flow cytometry. Proteins in ESPs were analyzed by electrophoresis; then, ESPs were classified as either differential or conserved. Differentially included proteins were MS-sequenced and functionally characterized. Only 4 of 10 ESPs induced Tregs. Proteins with catalytic activity and those involved in immunological processes predominated, supporting the idea that these molecules could play an important role in the induction of Tregs.

Efficacy of intravenous immunoglobulin in autoimmune neurological diseases. Literature systematic review and meta-analysis.

BACKGROUND: Corticosteroids are the first-line treatment for several common autoimmune neurological diseases. Other therapeutic approaches, including intravenous immunoglobulin (IVIg) and plasmapheresis, have shown mixed results in patient improvement. OBJECTIVE: To compare the efficacy of IVIg administration with that of corticosteroids, plasmapheresis, and placebo in autoimmune neurological diseases like Guillain-Barré syndrome, myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, optic neuritis, and multiple sclerosis. METHODS: A systematic review was performed on the databases PubMed, MEDLINE, Embase, and Cochrane. Controlled, randomized studies comparing the efficacy of IVIg with placebo, plasmapheresis, and/or glucocorticoid administration were selected. Only studies reporting the number of patients who improved after treatment were included, irrespective of language or publication year. In total, 23 reports were included in the meta-analysis study. RESULTS: Our meta-analysis showed a beneficial effect of IVIg administration on patient improvement over placebo (OR = 2.79, CI [95%] = 1.40-5.55, P = 0.01). Meanwhile, IVIg administration showed virtually identical effects to plasmapheresis (OR = 0.83, CI [95%] = 0.45-1.55, P < 0.01). Finally, no significant differences were found in the efficacy of IVIg and glucocorticoid administration (OR = 0.98, Cl [95%] = 0.58-1.68, P = 0.13). CONCLUSION: IVIg can be regarded as a viable therapeutic approach, either as a first- or second-line therapy, and as an adjuvant therapy for autoimmune neurological diseases.

Regulatory T Cells as an Escape Mechanism to the Immune Response in Taenia crassiceps Infection.

Murine cysticercosis by Taenia crassiceps is a model for human neurocysticercosis. Genetic and/or immune differences may underlie the higher susceptibility to infection in BALB/cAnN with respect to C57BL/6 mice. T regulatory cells (Tregs) could mediate the escape of T. crassiceps from the host immunity. This study is aimed to investigate the role of Tregs in T. crassiceps establishment in susceptible and non-susceptible mouse strains. Treg and effector cells were quantified in lymphoid organs before infection and 5, 30, 90, and 130 days post-infection. The proliferative response post-infection was characterized in vitro. The expression of regulatory and inflammatory molecules was assessed on days 5 and 30 post-infection. Depletion assays were performed to assess Treg functionality. Significantly higher Treg percentages were observed in BALB/cAnN mice, while increased percentages of activated CD127+ cells were found in C57BL/6 mice. The proliferative response was suppressed in susceptible mice, and Treg proliferation occurred only in susceptible mice. Treg-mediated suppression mechanisms may include IL-10 and TGFß secretion, granzyme- and perforin-mediated cytolysis, metabolic disruption, and cell-to-cell contact. Tregs are functional in BALB/cAnN mice. Therefore Tregs could be allowing parasite establishment and survival in susceptible mice but could play a homeostatic role in non-susceptible strains.

A novel, sequencing-free strategy for the functional characterization of Taenia solium proteomic fingerprint.

The flatworm Taenia solium causes human and pig cysticercosis. When cysticerci are established in the human central nervous system, they cause neurocysticercosis, a potentially fatal disease. Neurocysticercosis is a persisting public health problem in rural regions of Mexico and other developing countries of Latin America, Asia, and Africa, where the infection is endemic. The great variability observed in the phenotypic and genotypic traits of cysticerci result in a great heterogeneity in the patterns of molecules secreted by them within their host. This work is aimed to identify and characterize cysticercal secretion proteins of T. solium cysticerci obtained from 5 naturally infected pigs from Guerrero, Mexico, using 2D-PAGE proteomic analysis. The isoelectric point (IP) and molecular weight (MW) of the spots were identified using the software ImageMaster 2D Platinum v.7.0. Since most secreted proteins are impossible to identify by mass spectrometry (MS) due to their low concentration in the sample, a novel strategy to predict their sequence was applied. In total, 108 conserved and 186 differential proteins were identified in five cysticercus cultures. Interestingly, we predicted the sequence of 14 proteins that were common in four out of five cysticercus cultures, which could be used to design vaccines or diagnostic methods for neurocysticercosis. A functional characterization of all sequences was performed using the algorithms SecretomeP, SignalP, and BlastKOALA. We found a possible link between signal transduction pathways in parasite cells and human cancer due to deregulation in signal transduction pathways. Bioinformatics analysis also demonstrated that the parasite release proteins by an exosome-like mechanism, which could be of biological interest.