Gene and gene therapy
Posted: Sat Aug 08, 2020 12:11 pm
2020 Jul 15
Department of Pharmacology, School of Pharmaceutical Education and Research, India
Gene therapy, a novel therapeutic tool for neurological disorders: Current progress, challenges and future prospective
https://pubmed.ncbi.nlm.nih.gov/32674730/
Abstract
Neurological disorders are one of the major threat for health care system as it puts enormous socioeconomic burden. All aged population 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 are 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 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.
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2020 Jul 16
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Proposed minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life
https://pubmed.ncbi.nlm.nih.gov/32676761/
Abstract
Aim: The aim of this study was to identify the minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life.
Methods: We searched the Online Mendelian Inheritance in Man (OMIM) database to extract the validated human genes annotated (until March 2020) for five major disorders of pathophysiological overlap and sequential chronological occurrence in human, including multiple sclerosis, type 2 diabetes mellitus, Alzheimer's disease, vascular dementia, and Lewy body dementia. Gene co-expression and physical interaction networks were subsequently constructed for the overlapping genes across the selected disorders.
Results: Remarkably, each of the gene co-expression and physical interaction networks consisted of single clusters (P = 0.0005 and P = 1 × 10-16, respectively). APP was the major hub in the integrated and tissue-specific co-expression networks, whereas insulin was the major hub in the physical interaction network. Several other hubs were identified across the identified networks, including TNF, VEGFA, GAPDH, and NOTCH1.
Conclusion: We propose the minimal co-expression and physical interaction networks and their single clustering in the development of cognition impairment in human mid and late life. This is a pilot study, warranting identification of more risk genes, using additional validated databases in the future.
Department of Pharmacology, School of Pharmaceutical Education and Research, India
Gene therapy, a novel therapeutic tool for neurological disorders: Current progress, challenges and future prospective
https://pubmed.ncbi.nlm.nih.gov/32674730/
Abstract
Neurological disorders are one of the major threat for health care system as it puts enormous socioeconomic burden. All aged population 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 are 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 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.
---------------------------------------------------------------------------
2020 Jul 16
Department of Immunology, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
Proposed minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life
https://pubmed.ncbi.nlm.nih.gov/32676761/
Abstract
Aim: The aim of this study was to identify the minimal essential co-expression and physical interaction networks involved in the development of cognition impairment in human mid and late life.
Methods: We searched the Online Mendelian Inheritance in Man (OMIM) database to extract the validated human genes annotated (until March 2020) for five major disorders of pathophysiological overlap and sequential chronological occurrence in human, including multiple sclerosis, type 2 diabetes mellitus, Alzheimer's disease, vascular dementia, and Lewy body dementia. Gene co-expression and physical interaction networks were subsequently constructed for the overlapping genes across the selected disorders.
Results: Remarkably, each of the gene co-expression and physical interaction networks consisted of single clusters (P = 0.0005 and P = 1 × 10-16, respectively). APP was the major hub in the integrated and tissue-specific co-expression networks, whereas insulin was the major hub in the physical interaction network. Several other hubs were identified across the identified networks, including TNF, VEGFA, GAPDH, and NOTCH1.
Conclusion: We propose the minimal co-expression and physical interaction networks and their single clustering in the development of cognition impairment in human mid and late life. This is a pilot study, warranting identification of more risk genes, using additional validated databases in the future.
