Gene and gene therapy

[Petr75]

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.

[Petr75]

2020 Aug 11
Karolinska Schizophrenia Project (KaSP) consortium: NORMENT, Division of Mental Health and Addiction, Oslo University Hospital, Oslo, Norway
The genetic architecture of human brainstem structures and their involvement in common brain disorders
https://pubmed.ncbi.nlm.nih.gov/32782260/


Abstract

Brainstem regions support vital bodily functions, yet their genetic architectures and involvement in common brain disorders remain understudied. Here, using imaging-genetics data from a discovery sample of 27,034 individuals, we identify 45 brainstem-associated genetic loci, including the first linked to midbrain, pons, and medulla oblongata volumes, and map them to 305 genes. In a replication sample of 7432 participants most of the loci show the same effect direction and are significant at a nominal threshold. We detect genetic overlap between brainstem volumes and eight psychiatric and neurological disorders. In additional clinical data from 5062 individuals with common brain disorders and 11,257 healthy controls, we observe differential volume alterations in schizophrenia, bipolar disorder, multiple sclerosis, mild cognitive impairment, dementia, and Parkinson's disease, supporting the relevance of brainstem regions and their genetic architectures in common brain disorders.

[Petr75]

2020 Oct 15
Department of Neurology, Medical University of Plovdiv, Bulgaria
Association between TNFA, IL10 and IL18 promoter gene variants and cognitive functions in patients with relapsing-remitting multiple sclerosis
https://pubmed.ncbi.nlm.nih.gov/32795736/

Abstract

Objectives: To investigate the relationship between TNFA-308G > A, IL10-1082A > G, IL18-607C > A, and cognitive functioning in relapsing-remitting multiple sclerosis (RRMS).

Results: In the patients' group: AG genotype of TNFA-308G > A was associated with higher serum tumor necrosis factor-alpha (TNF-alpha) than GG genotype, and higher TNF-alpha levels correlated with poorer results on Symbol Digit Modalities Test; CC genotype of IL18-607C > A was related to lower score on Isaacs test, compared to AC variant; AA genotype of IL10-1082A > G was associated with abnormally low results on Paced Auditory Series Addition Test.

Conclusions: TNFA-308G > A, IL10-1082A > G and IL18-607C > A gene variants may be associated with impaired cognitive functions in RRMS patients.

[Petr75]

2020 Sep 17
Biological Science Department, Bharathiar University, Coimbatore, India
Exploring the role of gene therapy for neurological disorders
https://pubmed.ncbi.nlm.nih.gov/32940177/

Abstract

Gene therapy is one the frontier fields of medical breakthroughs that poses as an effective solution to previously incurable diseases. The delivery of the corrective genetic material or a therapeutic gene into the cell restores the missing gene function and cures a plethora of diseases, incurable by the conventional medical approaches. This discovery holds the potential to treat many neurodegenerative disorders such as muscular atrophy, multiple sclerosis, Parkinson's disease (PD) and Alzheimer's disease (AD) among others. Gene therapy proves as a humane, cost effective alternative to the exhaustive often arduous and timely impossible process of finding matched donors and extensive surgery. It also overcomes the shortcoming of conventional methods to cross the blood brain barrier. However, the use of gene therapy is only possible after procuring the in-depth knowledge of the immuno-pathogenesis and molecular mechanism of the disease. The process of gene therapy can be broadly categorized into three main steps: elucidating the target gene, culling the appropriate vector, and determining the best mode of transfer; each step mandating pervasive research. This review aims to dissertate and summarize the role, various vectors and methods of delivery employed in gene therapy with special emphasis on therapy directed at the central nervous system (CNS) associated with neurodegenerative diseases.