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https://www.readbyqxmd.com/read/27464072/pharmacogenetics-in-neurodegenerative-diseases-implications-for-clinical-trials
#1
Rosanna Tortelli, Davide Seripa, Francesco Panza, Vincenzo Solfrizzi, Giancarlo Logroscino
BACKGROUND: Pharmacogenetics has become extremely important over the last 20 years for identifying individuals more likely to be responsive to pharmacological interventions. The role of genetic background as a predictor of drug response is a young and mostly unexplored field in neurodegenerative diseases. SUMMARY: Mendelian mutations in neurodegenerative diseases have been used as models for early diagnosis and intervention. On the other hand, genetic polymorphisms or risk factors for late-onset Alzheimer's disease (AD) or other neurodegenerative diseases, probably influencing drug response, are hardly taken into account in randomized clinical trial (RCT) design...
2016: Frontiers of Neurology and Neuroscience
https://www.readbyqxmd.com/read/27397479/pharmacomodulation-of-microrna-expression-in-neurocognitive-diseases-obstacles-and-future-opportunities
#2
Viorel Simion, Wissem Deraredj Nadim, Hélène Benedetti, Chantal Pichon, Severine Morisset-Lopez, Patrick Baril
Given the importance of microRNAs (miRNAs) in modulating brain functions and their implications in neurocognitive disorders there are currently significant efforts devoted in the field of miRNA-based therapeutics to correct and/or to treat these brain diseases. The observation that miRNA 29a/b-1 cluster, miRNA 10b and miRNA 7, for instance, are frequently deregulated in the brains of patients with neurocognitive diseases and in animal models of Alzheimer, Huntington's and Parkinson's diseases, suggest that correction of miRNA expression using agonist or antagonist miRNA oligonucleotides might be a promising approach to correct or even to cure such diseases...
June 30, 2016: Current Neuropharmacology
https://www.readbyqxmd.com/read/27346026/derivation-of-huntington-disease-affected-genea090-human-embryonic-stem-cell-line
#3
Biljana Dumevska, Julia Schaft, Robert McKernan, Jesselyn Hu, Uli Schmidt
The Genea090 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a pluritest pluripotency score of 30.91, novelty of 1...
March 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27346022/derivation-of-huntington-disease-affected-genea017-human-embryonic-stem-cell-line
#4
Biljana Dumevska, Robert McKernan, Divya Goel, Uli Schmidt, Teija Peura
The Genea017 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, genetic analysis confirmed a 46, XY karyotype and male allele pattern through CGH and STR analysis. The hESC line had pluripotent cell morphology, 87% of cells expressed Nanog, 95% Oct4, 88% Tra1-60 and 99% SSEA4, gave a PluriTest pluripotency score of 34.74, novelty of 1...
March 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27346013/derivation-of-huntington-disease-affected-genea091-human-embryonic-stem-cell-line
#5
Biljana Dumevska, Julia Schaft, Robert McKernan, Jesselyn Hu, Uli Schmidt
The Genea091 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 40 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 92% of cells expressed Nanog, 97% Oct4, 79% Tra1-60 and 98% SSEA4 and gave a Pluritest pluripotency score of 38.36, Novelty of 1...
March 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27346012/derivation-of-huntington-disease-affected-genea046-human-embryonic-stem-cell-line
#6
Biljana Dumevska, Omar Chami, Robert McKernan, Divya Goel, Uli Schmidt
The Genea046 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying HTT gene CAG expansion of 45 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 85% of cells expressed Nanog, 92% Oct4, 75% Tra1-60 and 99% SSEA4 and demonstrated Alkaline Phosphatase activity. The cell line was negative for Mycoplasma and visible contamination...
March 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27346008/derivation-of-huntington-disease-affected-genea089-human-embryonic-stem-cell-line
#7
Biljana Dumevska, Robert McKernan, Jesselyn Hu, Uli Schmidt
The Genea089 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 41 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 91% of cells expressed Nanog, 95% Oct4, 90% Tra1-60 and 100% SSEA4 and gave a PluriTest Pluripotency score of 39.28, Novelty of 1...
March 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27346007/derivation-of-huntington-disease-affected-genea020-human-embryonic-stem-cell-line
#8
Biljana Dumevska, Teija Peura, Robert McKernan, Divya Goel, Uli Schmidt
The Genea020 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 48 repeats, indicative of Huntington disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female allele pattern. The hESC line had pluripotent cell morphology, 89% of cells expressed Nanog, 95% Oct4, 29% Tra1-60 and 99% SSEA4, gave a Pluritest pluripotency score of 27.51, novelty of 1...
March 2016: Stem Cell Research
https://www.readbyqxmd.com/read/27346005/derivation-of-huntington-disease-affected-genea018-human-embryonic-stem-cell-line
#9
Biljana Dumevska, Heather Main, Robert McKernan, Divya Goel, Uli Schmidt, Teija Peura
The Genea018 human embryonic stem cell line was derived from a donated, fully commercially consented ART blastocyst, carrying Htt gene CAG expansion of 46 repeats, indicative of Huntington Disease. Following ICM outgrowth on inactivated human feeders, karyotype was confirmed as 46, XX by CGH and STR analysis demonstrated a female Allele pattern. The hESC line had pluripotent cell morphology, 75% of cells expressed Nanog, 91% Oct4, 73% Tra1-60 and 96% SSEA4, gave a Pluritest pluripotency score of 31.12, Novelty of 1...
March 2016: Stem Cell Research
https://www.readbyqxmd.com/read/26544700/the-risk-of-viral-rebound-in-the-year-after-delivery-in-women-remaining-on-antiretroviral-therapy
#10
Susie Huntington, Claire Thorne, Marie-Louise Newell, Jane Anderson, Graham P Taylor, Deenan Pillay, Teresa Hill, Pat A Tookey, Caroline Sabin
OBJECTIVE: The objective of this study is to assess the risk of viral rebound in postpartum women on suppressive combination antiretroviral therapy (cART). METHODS: Using data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC), women with HIV-RNA 50 copies/ml or less at delivery in 2006-2011, who started life-long cART during pregnancy (n = 321) or conceived on cART (n = 618), were matched by age, duration on cART and time period, with at least one control (non-postpartum)...
November 2015: AIDS
https://www.readbyqxmd.com/read/25710412/pregnancy-is-associated-with-elevation-of-liver-enzymes-in-hiv-positive-women-on-antiretroviral-therapy
#11
Susie Huntington, Claire Thorne, Marie-Louise Newell, Jane Anderson, Graham P Taylor, Deenan Pillay, Teresa Hill, Pat A Tookey, Caroline Sabin
OBJECTIVE: The objective of this study is to assess whether pregnancy is associated with an increased risk of liver enzyme elevation (LEE) and severe LEE in HIV-positive women on antiretroviral therapy (ART). DESIGN: Two observational studies: the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC). METHODS: Combined data from UK CHIC and NSHPC were used to identify factors associated with LEE (grade 1-4) and severe LEE (grade 3-4)...
April 24, 2015: AIDS
https://www.readbyqxmd.com/read/25684727/toward-sophisticated-basal-ganglia-neuromodulation-review-on-basal-ganglia-deep-brain-stimulation
#12
REVIEW
Claudio Da Cunha, Suelen L Boschen, Alexander Gómez-A, Erika K Ross, William S J Gibson, Hoon-Ki Min, Kendall H Lee, Charles D Blaha
This review presents state-of-the-art knowledge about the roles of the basal ganglia (BG) in action-selection, cognition, and motivation, and how this knowledge has been used to improve deep brain stimulation (DBS) treatment of neurological and psychiatric disorders. Such pathological conditions include Parkinson's disease, Huntington's disease, Tourette syndrome, depression, and obsessive-compulsive disorder. The first section presents evidence supporting current hypotheses of how the cortico-BG circuitry works to select motor and emotional actions, and how defects in this circuitry can cause symptoms of the BG diseases...
November 2015: Neuroscience and Biobehavioral Reviews
https://www.readbyqxmd.com/read/25393995/does-pregnancy-increase-the-risk-of-art-induced-hepatotoxicity-among-hiv-positive-women
#13
Susie Huntington, Claire Thorne, Jane Anderson, Marie-Louise Newell, Graham Taylor, Deenan Pillay, Teresa Hill, Pat Tookey, Caroline Sabin
INTRODUCTION: High rates of hepatotoxicity have been observed among HIV-positive pregnant women using antiretroviral therapy (ART). However, the extent to which pregnancy affects the risk of ART-induced hepatotoxicity is unclear since studies in this area have generated conflicting results. MATERIAL AND METHODS: Combined data from the UK Collaborative HIV Cohort (UK CHIC) study and the UK and Ireland National Study of HIV in Pregnancy and Childhood (NSHPC) were used...
2014: Journal of the International AIDS Society
https://www.readbyqxmd.com/read/25319671/invited-review-decoding-the-pathophysiological-mechanisms-that-underlie-rna-dysregulation-in-neurodegenerative-disorders-a-review-of-the-current-state-of-the-art
#14
REVIEW
Matthew J Walsh, Johnathan Cooper-Knock, Jennifer E Dodd, Matthew J Stopford, Simeon R Mihaylov, Janine Kirby, Pamela J Shaw, Guillaume M Hautbergue
Altered RNA metabolism is a key pathophysiological component causing several neurodegenerative diseases. Genetic mutations causing neurodegeneration occur in coding and noncoding regions of seemingly unrelated genes whose products do not always contribute to the gene expression process. Several pathogenic mechanisms may coexist within a single neuronal cell, including RNA/protein toxic gain-of-function and/or protein loss-of-function. Genetic mutations that cause neurodegenerative disorders disrupt healthy gene expression at diverse levels, from chromatin remodelling, transcription, splicing, through to axonal transport and repeat-associated non-ATG (RAN) translation...
February 2015: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/25248568/molecular-neurodegeneration-basic-biology-and-disease-pathways
#15
EDITORIAL
Robert Vassar, Hui Zheng
The field of neurodegeneration research has been advancing rapidly over the past few years, and has provided intriguing new insights into the normal physiological functions and pathogenic roles of a wide range of molecules associated with several devastating neurodegenerative disorders, including Alzheimer's disease, Parkinson's disease, amyotrophic lateral sclerosis, frontotemporal dementia, Huntington's disease, and Down syndrome. Recent developments have also facilitated initial efforts to translate preclinical discoveries toward novel therapeutic approaches and clinical trials in humans...
2014: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/25164826/antioxidative-defense-mechanisms-controlled-by-nrf2-state-of-the-art-and-clinical-perspectives-in-neurodegenerative-diseases
#16
REVIEW
Jamie L Lim, Micha M M Wilhelmus, Helga E de Vries, Benjamin Drukarch, Jeroen J M Hoozemans, Jack van Horssen
Activation of microglial cells and impaired mitochondrial function are common pathological characteristics of many neurological diseases and contribute to increased generation of reactive oxygen species (ROS). It is nowadays accepted that oxidative damage and mitochondrial dysfunction are key hallmarks of classical neuroinflammatory and neurodegenerative diseases, such as multiple sclerosis, Alzheimer's disease, Parkinson's disease and Huntington's disease. To counteract the detrimental effects of ROS and restore the delicate redox balance in the central nervous system (CNS), cells are equipped with an endogenous antioxidant defense mechanism consisting of several antioxidant enzymes...
October 2014: Archives of Toxicology
https://www.readbyqxmd.com/read/24593018/response-to-antiretroviral-therapy-art-comparing-women-with-previous-use-of-zidovudine-monotherapy-zdvm-in-pregnancy-with-art-na%C3%A3-ve-women
#17
Susie Huntington, Claire Thorne, Jane Anderson, Marie-Louise Newell, Graham P Taylor, Deenan Pillay, Teresa Hill, Pat Tookey, Caroline Sabin
BACKGROUND: Short-term zidovudine monotherapy (ZDVm) remains an option for some pregnant HIV-positive women not requiring treatment for their own health but may affect treatment responses once antiretroviral therapy (ART) is subsequently started. METHODS: Data were obtained by linking two UK studies: the UK Collaborative HIV Cohort (UK CHIC) study and the National Study of HIV in Pregnancy and Childhood (NSHPC). Treatment responses were assessed for 2028 women initiating ART at least one year after HIV-diagnosis...
March 4, 2014: BMC Infectious Diseases
https://www.readbyqxmd.com/read/24285315/the-potential-of-carbon-11-and-fluorine-18-chemistry-illustration-through-the-development-of-positron-emission-tomography-radioligands-targeting-the-translocator-protein-18%C3%A2-kda
#18
REVIEW
Annelaure Damont, Dirk Roeda, Frédéric Dollé
The TSPO (translocator protein), also known as the peripheral benzodiazepine receptor, is upregulated in the brain of subjects suffering from neurodegenerative disorders such as Alzheimer's, Parkinson's and Huntington's disease. Moreover, this overexpression has been proved to be linked to microglia activation making thus the TSPO a marker of choice of neuroinflammatory processes and therefore a potential target for the development of radioligands for positron emission tomography imaging. The discovery of selective TSPO ligands and their labelling with the short-lived positron-emitter isotopes carbon-11 and fluorine-18 emerged in the mid-1980s with the preparation of the 3-isoquinolinecarboxamide [(11) C]PK11195...
March 2013: Journal of Labelled Compounds & Radiopharmaceuticals
https://www.readbyqxmd.com/read/23861482/alterations-in-the-frequency-of-trinucleotide-repeat-dynamic-mutations-in-offspring-conceived-through-assisted-reproductive-technology
#19
Ying-Ming Zheng, Li Li, Li-Ming Zhou, Fang Le, Li-Yi Cai, Ping Yu, Yu-Rong Zhu, Xiao-Zhen Liu, Li-Ya Wang, Le-Jun Li, Yi-Yun Lou, Xiang-Rong Xu, Hang-Ying Lou, Xiao-Ming Zhu, Jian-Zhong Sheng, He-Feng Huang, Fan Jin
STUDY QUESTION: How does the frequency of trinucleotide repeat dynamic mutations in offspring conceived through assisted reproductive technology (ART) compare with the frequency of these mutations in control offspring conceived from spontaneous pregnancies? SUMMARY ANSWER: There is a slight increase in dynamic mutation instability in offspring conceived through ART compared with the naturally conceived offspring. WHAT IS KNOWN ALREADY: There is evidence to suggest that ART can increase the risk of birth defects and karyotypic abnormalities...
September 2013: Human Reproduction
https://www.readbyqxmd.com/read/23700209/gene-therapy-for-misfolding-protein-diseases-of-the-central-nervous-system
#20
REVIEW
Waldy San Sebastian, Lluis Samaranch, Adrian P Kells, John Forsayeth, Krystof S Bankiewicz
Protein aggregation as a result of misfolding is a common theme underlying neurodegenerative diseases. Accordingly, most recent studies aim to prevent protein misfolding and/or aggregation as a strategy to treat these pathologies. For instance, state-of-the-art approaches, such as silencing protein overexpression by means of RNA interference, are being tested with positive outcomes in preclinical models of animals overexpressing the corresponding protein. Therapies designed to treat central nervous system diseases should provide accurate delivery of the therapeutic agent and long-term or chronic expression by means of a nontoxic delivery vehicle...
July 2013: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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