scholarly journals Gene therapy using viral vectors for acute neurologic insults

2000 ◽  
Vol XXXII (1-2) ◽  
pp. 82-82
Author(s):  
R. Sapolsky ◽  
G. Steinberg
Keyword(s):  
Gene Therapy ◽  
Brain Tissue ◽  
Viral Vectors ◽  
Molecular Processes ◽  
Hypoxia Ischemia ◽  
The Brain

Currently, many studies are devoted to the cellular and molecular processes occurring during the death of neurons due to hypoxia - ischemia of the brain tissue.

scholarly journals Safety profile of the transcription factor EB (TFEB)-based gene therapy through intracranial injection in mice

2020 ◽  
Vol 11 (1) ◽  
pp. 241-250
Author(s):  
Zhenyu Li ◽  
Guangqian Ding ◽  
Yudi Wang ◽  
Zelong Zheng ◽  
Jianping Lv
Keyword(s):  
Gene Therapy ◽  
Transcription Factor ◽  
Neurodegenerative Diseases ◽  
Brain Tissue ◽  
Inflammatory Responses ◽  
Tissue Samples ◽  
Protein Levels ◽  
Virus Serotype ◽  
Transcription Factor Eb ◽  
The Brain

AbstractTranscription factor EB (TFEB)-based gene therapy is a promising therapeutic strategy in treating neurodegenerative diseases by promoting autophagy/lysosome-mediated degradation and clearance of misfolded proteins that contribute to the pathogenesis of these diseases. However, recent findings have shown that TFEB has proinflammatory properties, raising the safety concerns about its clinical application. To investigate whether TFEB induces significant inflammatory responses in the brain, male C57BL/6 mice were injected with phosphate-buffered saline (PBS), adeno-associated virus serotype 8 (AAV8) vectors overexpressing mouse TFEB (pAAV8-CMV-mTFEB), or AAV8 vectors expressing green fluorescent proteins (GFPs) in the barrel cortex. The brain tissue samples were collected at 2 months after injection. Western blotting and immunofluorescence staining showed that mTFEB protein levels were significantly increased in the brain tissue samples of mice injected with mTFEB-overexpressing vectors compared with those injected with PBS or GFP-overexpressing vectors. pAAV8-CMV-mTFEB injection resulted in significant elevations in the mRNA and protein levels of lysosomal biogenesis indicators in the brain tissue samples. No significant changes were observed in the expressions of GFAP, Iba1, and proinflammation mediators in the pAAV8-CMV-mTFEB-injected brain compared with those in the control groups. Collectively, our results suggest that AAV8 successfully mediates mTFEB overexpression in the mouse brain without inducing apparent local inflammation, supporting the safety of TFEB-based gene therapy in treating neurodegenerative diseases.

Gene Therapy, A Novel Therapeutic Tool for Neurological Disorders: Current Progress, Challenges and Future Prospective

2020 ◽  
Vol 20 (3) ◽  
pp. 184-194 ◽  
Author(s):  
Ashif Iqubal ◽  
Mohammad Kashif Iqubal ◽  
Aamir Khan ◽  
Javed Ali ◽  
Sanjula Baboota ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Targeted Delivery ◽  
Neurological Disorders ◽  
Viral Vectors ◽  
Gene Selection ◽  
Current Status ◽  
Lysosomal Storage ◽  
Molecular Etiology ◽  
The Brain ◽  
Lateral Sclerosis

: Neurological disorders are one of the major threat for health care system as they put enormous socioeconomic burden. All aged populations are susceptible to one or other neurological problems with symptoms of neuroinflammation, neurodegeneration and cognitive dysfunction. At present, available pharmacotherapeutics are insufficient to treat these diseased conditions and in most cases, they provide only palliative effect. It was also found that the molecular etiology of neurological disorders is directly linked with the alteration in genetic makeup, which can be inherited or triggered by the injury, environmental toxins and by some existing disease. Therefore, to take care of this situation, gene therapy has emerged as an advanced modality that claims to permanently cure the disease by deletion, silencing or edition of faulty genes and by insertion of healthier genes. In this modality, vectors (viral and non-viral) are used to deliver targeted gene into a specific region of the brain via various routes. At present, gene therapy has shown positive outcomes in complex neurological disorders, such as Parkinson's disease, Alzheimer's disease, Huntington disease, Multiple sclerosis, Amyotrophic lateral sclerosis and in lysosomal storage disease. However, there are some limitations such as immunogenic reactions non-specificity of viral vectors and a lack of effective biomarkers to understand the efficacy of therapy. Considerable progress has been made to improve vector design, gene selection and targeted delivery. This review article deals with the current status of gene therapy in neurological disorders along with its clinical relevance, challenges and future prospective.

Gene therapy based on lipid nanoparticles as non-viral vectors for Gliomas treatment

2020 ◽  
Vol 20 ◽  
Author(s):  
Marcela Tavares Luiz ◽  
Larissa Bueno Tofani ◽  
Victor Hugo Sousa Araújo ◽  
Leonardo Delello Di Filippo ◽  
Jonatas Lobato Duarte ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Multidrug Resistance ◽  
Viral Vectors ◽  
Lipid Nanoparticles ◽  
Resistance Mechanisms ◽  
Target Cells ◽  
Promising Strategy ◽  
Cellular Apoptosis ◽  
The Brain ◽  
Astrocytoma Grade Iv

Abstract:: Gliomas are primary brain tumors originating from glial cells, representing 30% of all Central Nervous System (CNS) neoplasia. Among them, the astrocytoma grade IV (glioblastoma multiforme) is the most common presenting an invasive and aggressive profile, with an estimated life expectancy about 15 months after diagnosis even after treatment with radiation, surgical resection, and chemotherapy. This poor prognostic is related to the presence of the blood-brain barrier (BBB) and multidrug resistance mechanisms that avoid the uptake and retention of chemotherapeutics inside the brain. Gene therapy has been a promising strategy to overcome these treatment limitations since it has the ability to modify the defective genetic information in tumor cells, being able to induce cellular apoptosis, and silencing genes responsible for multidrug resistance. Lipid-based nanoparticles, non-viral vectors, have been investigated to deliver genes across the BBB to reach the gliomas cells target. Besides that, its low immunogenicity, easy production, ability in the incorporation of ligands to specific target cells and capacity to carry higher size genes, has become the gene therapy based on non-viral vectors promising glioma treatment. In this context, this review will address the most common non-viral vectors based on lipid-based nanoparticles used for gliomas gene therapy such as liposomes, solid lipid nanoparticles, nanostructured lipid carriers and nanoemulsions.

scholarly journals INFECTIOUS EXACERBATION OF BRONCHIECTASIS SUCCESSFULLY TREATED WITH CEFTRIAXONE/SULBACTAM/DISODIUM EDETATE-1034 (ELORES™)

2017 ◽  
Vol 10 (2) ◽  
pp. 407
Author(s):  
Ninik Mudjihartini
Keyword(s):  
Brain Tissue ◽  
Hemorrhagic Stroke ◽  
Hypoxic Condition ◽  
Normal Subjects ◽  
The Elderly ◽  
Health Concern ◽  
Stroke Patients ◽  
Significant Difference ◽  
Hypoxia Ischemia ◽  
The Brain

Objective: Strokes remain a significant health concern and are the highest cause of mortality and physical or mental disability in productive and the elderly hospitalized patients in Indonesia. Neuroglobin (Ngb) mostly located in the central and peripheral nervous system, predicted enhanced neuronal survival under hypoxic condition, such as in a stroke. The aim of this study is to observe the response of the brain tissue of hemorrhagic stroke patients against hypoxic/ischemic conditions. The objectives are to recognize the pattern of Ngb expression in the brain tissue and plasma of hemorrhagic stroke patients, and furthermore, to compare the level of Ngb in the brain tissue and plasma of hemorrhagic stroke patients.Methods: This is an observational study with consecutive sampling methods using cerebral cortex and the blood of hemorrhagic stroke patients, who underwent craniotomies to evacuate hematomas at Cipto Mangunkusumo Hospital (RSCM) and other hospitals in Jakarta. Ngb expression was measured in brain tissue and blood using real time reverse transcription polymerase chain reaction, while the ELISA method was adopted to measure Ngb protein in plasma.Results: Hypoxia/ischemia in the brain tissue of hemorrhagic stroke patients increased the expression of Ngb in brain tissue compared to the blood. The level of Ngb protein in plasma of hemorrhagic stroke patients increased significantly compared to normal subjects; however, there is no significant difference between the plasma and brain tissue of hemorrhagic stroke patients.Conclusion: Hypoxia/ischemia in hemorrhagic stroke patients increases the expression of Ngb mRNA and protein level.Keywords: Neuroglobin, Hypoxia, Hemorrhagic stroke.

scholarly journals Gene Therapy to Modulate Alpha-Synuclein in Synucleinopathies

2021 ◽  
pp. 1-9
Author(s):  
Ivette M. Sandoval ◽  
David J. Marmion ◽  
Kimberly T. Meyers ◽  
Fredric P. Manfredsson
Keyword(s):  
Gene Expression ◽  
Gene Therapy ◽  
Neuronal Death ◽  
Viral Vectors ◽  
Alpha Synuclein ◽  
Molecular Processes ◽  
Therapeutic Modalities ◽  
Neurodegenerative Process ◽  
Lysosomal Dysfunction ◽  
Traditional Sense

The protein alpha-Synuclein (α-Syn) is a key contributor to the etiology of Parkinson’s disease (PD) with aggregation, trans-neuronal spread, and/or depletion of α-Syn being viewed as crucial events in the molecular processes that results in neurodegeneration. The exact succession of pathological occurrences that lead to neuronal death are still largely unknown and are likely to be multifactorial in nature. Despite this unknown, α-Syn dose and stability, autophagy-lysosomal dysfunction, and inflammation, amongst other cellular impairments, have all in been described as participatory events in the neurodegenerative process. To that end, in this review we discuss the logical points for gene therapy to intervene in α-Syn-mediated disease and review the preclinical body of work where gene therapy has been used, or could conceptually be used, to ameliorate α-Syn induced neurotoxicity. In this review, we discuss gene therapy in the traditional sense of modulating gene expression, as well as the use of viral vectors and nanoparticles as methods to deliver other therapeutic modalities.

Liquid Chromatography Analysis of Clozapine in Rat Brain Tissue, Using its Molecularly Imprinted Polymer after Administration of Toxic Dose of Drug and Lipid Emulsion Therapy

2019 ◽  
Vol 15 (3) ◽  
pp. 251-257
Author(s):  
Bahareh Sadat Yousefsani ◽  
Seyed Ahmad Mohajeri ◽  
Mohammad Moshiri ◽  
Hossein Hosseinzadeh
Keyword(s):  
Rat Brain ◽  
Brain Tissue ◽  
Molecularly Imprinted Polymer ◽  
Lipid Emulsion ◽  
Limit Of Detection ◽  
Imprinted Polymer ◽  
Toxic Dose ◽  
Molecularly Imprinted ◽  
The Brain ◽  
Rat Brain Tissue

Background:Molecularly imprinted polymers (MIPs) are synthetic polymers that have a selective site for a given analyte, or a group of structurally related compounds, that make them ideal polymers to be used in separation processes.Objective:An optimized molecularly imprinted polymer was selected and applied for selective extraction and analysis of clozapine in rat brain tissue.Methods:A molecularly imprinted solid-phase extraction (MISPE) method was developed for preconcentration and cleanup of clozapine in rat brain samples before HPLC-UV analysis. The extraction and analytical process was calibrated in the range of 0.025-100 ppm. Clozapine recovery in this MISPE process was calculated between 99.40 and 102.96%. The limit of detection (LOD) and the limit of quantification (LOQ) of the assay were 0.003 and 0.025 ppm, respectively. Intra-day precision values for clozapine concentrations of 0.125 and 0.025 ppm were 5.30 and 3.55%, whereas inter-day precision values of these concentrations were 9.23 and 6.15%, respectively. In this study, the effect of lipid emulsion infusion in reducing the brain concentration of drug was also evaluated.Results:The data indicated that calibrated method was successfully applied for the analysis of clozapine in the real rat brain samples after administration of a toxic dose to animal. Finally, the efficacy of lipid emulsion therapy in reducing the brain tissue concentration of clozapine after toxic administration of drug was determined.Conclusion:The proposed MISPE method could be applied in the extraction and preconcentration before HPLC-UV analysis of clozapine in rat brain tissue.

Sign in / Sign up

Export Citation Format

Share Document