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Gene therapy chronic pain

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https://www.readbyqxmd.com/read/29150266/interleukin-35-and-hepatocyte-growth-factor-as-a-novel-combined-immune-gene-therapy-for-multiple-sclerosis-disease
#1
Samira Moghadam, Maryam Erfanmanesh, Abdolreza Esmaeilzadeh
An autoimmune demyelination disease of the Central Nervous System, Multiple Sclerosis, is a chronic inflammation which mostly involves young adults. Suffering people face functional loss with a severe pain. Most current MS treatments are focused on the immune response suppression. Approved drugs suppress the inflammatory process, but factually, there is no definite cure for Multiple Sclerosis. Recently developed knowledge has demonstrated that gene and cell therapy as a hopeful approach in tissue regeneration...
November 2017: Medical Hypotheses
https://www.readbyqxmd.com/read/29130055/gene-therapy-with-hsv-encoding-p55tnfr-gene-for-hiv-neuropathic-pain-an-evidence-based-mini-review
#2
Hirotsugu Kanda, Shue Liu, Megumi Kanao, Hyun Yi, Takafumi Iida, Wan Huang, Takayuki Kunisawa, David A Lubarsky, Shuanglin Hao
While effective antiretroviral treatment makes human immunodeficiency virus (HIV)-related death decreased dramatically, neuropathic pain becomes one of the most common complications in patients with HIV/acquired immunodeficiency syndrome (AIDS). The exact mechanisms of HIV-related neuropathic pain are not well understood yet, and no effective therapy is for HIV-pain. Evidence has shown that proinflammatory factors (e.g., tumor necrosis factor alpha (TNFα)) released from glia, are critical to contributing to chronic pain...
2017: Translational Perioperative and Pain Medicine
https://www.readbyqxmd.com/read/29113923/effects-of-spinal-non-viral-interleukin-10-gene-therapy-formulated-with-d-mannose-in-neuropathic-interleukin-10-deficient-mice-behavioral-characterization-mrna-and-protein-analysis-in-pain-relevant-tissues
#3
Arden G Vanderwall, Shahani Noor, Melody S Sun, Jacob E Sanchez, Xuexian O Yang, Lauren L Jantzie, Nikolaos Mellios, Erin D Milligan
Studies show that spinal (intrathecal; i.t.) interleukin-10 (IL-10) gene therapy reverses neuropathic pain in animal models, and co-administration with the mannose receptor (MR; CD206) ligand d-mannose (DM) greatly improves therapeutic efficacy. However, the actions of endogenous IL-10 may be required for enduring pain control observed following i.t. IL-10 gene therapy, potentially narrowing the application of this non-viral transgene delivery approach. Here, we show that i.t. application of naked plasmid DNA expressing the IL-10 transgene co-injected with DM (DM/pDNA-IL-10) for the treatment of peripheral neuropathic pain in IL-10 deficient (IL-10 KO) mice results in a profound and prolonged bilateral pain suppression...
November 4, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29093260/-a-case-of-gitelman-syndrome-with-physical-retardation
#4
Juan Huang, Xiangrong Zheng, Dandan Guo, Guoyuan Zhang, Xia Wang, Chentao Liu
Gitelman syndrome is a rare disease. It is easy to be misdiagnosed and missed diagnosis due to the diverse clinical symptoms. A girl with long-term hypokalemia, who presented with intermittent pain of lower limb muscle and physical retardation, was treated in Xiangya Hospital, Central South University. Laboratory examination confirmed the severe hypokalemia and metabolic alkalosis. Gene sequencing indicated SLC12A3 gene mutation and the patient was finally diagnosed as Gitelman syndrome. Patients with chronic hypokalemia and metabolic alkalosis need to conduct gene sequencing to confirm the diagnosis...
October 28, 2017: Zhong Nan da Xue Xue Bao. Yi Xue Ban, Journal of Central South University. Medical Sciences
https://www.readbyqxmd.com/read/29084074/clinical-and-symptom-scores-are-significantly-correlated-with-fecal-microbiota-features-in-patients-with-symptomatic-uncomplicated-diverticular-disease-a-pilot-study
#5
Charlotte L Kvasnovsky, Lex E X Leong, Jocelyn M Choo, Guy C J Abell, Savvas Papagrigoriadis, Kenneth D Bruce, Geraint B Rogers
BACKGROUND: There is growing consensus that symptomatic uncomplicated diverticular disease is a chronic inflammatory condition, and that alterations in the fecal microbiota may contribute to its pathogenesis. OBJECTIVE: The aim of this study was to relate the fecal microbiota composition in symptomatic uncomplicated diverticular disease to measures of inflammation, symptoms, and history of previous acute diverticulitis. PARTICIPANTS AND METHODS: Fecal microbiota composition in 28 individuals with symptomatic uncomplicated diverticular disease was characterized by 16S RNA gene amplicon sequencing...
October 27, 2017: European Journal of Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/29075135/dnmt3a-methylation-in-neuropathic-pain
#6
Cuijie Shao, Yong Gao, Dan Jin, Xin Xu, Shuying Tan, Hui Yu, Qingxiang Zhao, Li Zhao, Wansheng Wang, Deqiang Wang
BACKGROUND: Mu opioid receptor (MOR) plays a crucial role in mediating analgesic effects of opioids and is closely associated with the pathologies of neuropathic pain. Previous studies have reported that peripheral nerve injury downregulates MOR expression, but the epigenetic mechanisms remain unknown. OBJECTIVE: Therefore, we investigated DNA methyltransferase3a (DNMT3a) expression or methylation changes within MOR promoter in the spinal cord in a neuropathic pain induced by a chronic constriction injury (CCI) mouse model and further determined whether these injury-associated changes are reversible by pharmacological interventions...
2017: Journal of Pain Research
https://www.readbyqxmd.com/read/29057994/effects-of-herpes-simplex-virus-vectors-encoding-poreless-trpv1-or-protein-phosphatase-1%C3%AE-in-a-rat-cystitis-model-induced-by-hydrogen-peroxide
#7
S Takai, T Majima, B Reinhart, W F Goins, Y Funahashi, M Gotoh, P Tyagi, J C Glorioso, N Yoshimura
Enhanced afferent excitability is considered to be an important pathophysiological basis of interstitial cystitis/bladder pain syndrome (IC/BPS). In addition, transient receptor potential vanilloid-1 (TRPV1) receptors are known to be involved in afferent sensitization. Animals with hydrogen peroxide (HP)-induced cystitis have been used as a model exhibiting pathologic characteristics of chronic inflammatory condition of the bladder. This study investigated the effect of gene therapy with replication-defective herpes simplex virus (HSV) vectors encoding poreless TRPV1 (PL) or protein phosphatase 1 α (PP1α), a negative regulator of TRPV1, using a HP-induced rat model of cystitis...
October 20, 2017: Gene Therapy
https://www.readbyqxmd.com/read/29046485/dimethyl-fumarate-increases-fetal-hemoglobin-provides-heme-detoxification-and-corrects-anemia-in-sickle-cell-disease
#8
Sriram Krishnamoorthy, Betty Pace, Dipti Gupta, Sarah Sturtevant, Biaoru Li, Levi Makala, Julia Brittain, Nancy Moore, Benjamin F Vieira, Timothy Thullen, Ivan Stone, Huo Li, William E Hobbs, David R Light
Sickle cell disease (SCD) results from a point mutation in the β-globin gene forming hemoglobin S (HbS), which polymerizes in deoxygenated erythrocytes, triggering recurrent painful vaso-occlusive crises and chronic hemolytic anemia. Reactivation of fetal Hb (HbF) expression ameliorates these symptoms of SCD. Nuclear factor (erythroid derived-2)-like 2 (Nrf2) is a transcription factor that triggers cytoprotective and antioxidant pathways to limit oxidative damage and inflammation and increases HbF synthesis in CD34+ stem cell-derived erythroid progenitors...
October 19, 2017: JCI Insight
https://www.readbyqxmd.com/read/29032938/the-jak-stat-signaling-pathway-and-photobiomodulation-in-chronic-wound-healing
#9
Sandy W Jere, Heidi Abrahamse, Nicolette N Houreld
Wound healing is a physiological process that occurs in overlapping phases namely hemostasis, inflammation, proliferation, and remodeling. Chronic wounds fail to proceed through these reparative processes to achieve the functional integrity within the expected time. Wound healing relies upon growth factors and cytokines for the precise and accurate regulation of cellular responses. These are achieved through the use of complex growth factor/cytokine induced signaling pathways. The Janus kinase/signal transducers and activators of transcription (JAK/STAT) pathway transmits extracellular signals to the nucleus for the transcription of genes involved in proliferation and differentiation, to name but a few...
October 6, 2017: Cytokine & Growth Factor Reviews
https://www.readbyqxmd.com/read/29022756/soluble-guanylyl-cyclase-is-a-critical-regulator-of-migraine-associated-pain
#10
Manel Ben Aissa, Alycia F Tipton, Zachariah Bertels, Ronak Gandhi, Laura S Moye, Madeline Novack, Brian M Bennett, Yueting Wang, Vladislav Litosh, Sue H Lee, Irina N Gaisina, Gregory Rj Thatcher, Amynah A Pradhan
Background Nitric oxide (NO) has been heavily implicated in migraine. Nitroglycerin is a prototypic NO-donor, and triggers migraine in humans. However, nitroglycerin also induces oxidative/nitrosative stress and is a source of peroxynitrite - factors previously linked with migraine etiology. Soluble guanylyl cyclase (sGC) is the high affinity NO receptor in the body, and the aim of this study was to identify the precise role of sGC in acute and chronic migraine. Methods We developed a novel brain-bioavailable sGC stimulator (VL-102), and tested its hyperalgesic properties in mice...
January 1, 2017: Cephalalgia: An International Journal of Headache
https://www.readbyqxmd.com/read/29021995/tumor-induced-osteomalacia
#11
Pablo Florenzano, Rachel I Gafni, Michael T Collins
Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome clinically characterized by bone pain, fractures and muscle weakness. It is caused by tumoral overproduction of fibroblast growth factor 23 (FGF23) that acts primarily at the proximal renal tubule, decreasing phosphate reabsorption and 1α-hydroxylation of 25 hydroxyvitamin D, thus producing hypophosphatemia and osteomalacia. Lesions are typically small, benign mesenchymal tumors that may be found in bone or soft tissue, anywhere in the body...
December 2017: Bone Reports
https://www.readbyqxmd.com/read/28967365/hypermobility-the-ehlers-danlos-syndromes-and-chronic-pain
#12
REVIEW
Delfien Syx, Inge De Wandele, Lies Rombaut, Fransiska Malfait
Chronic widespread pain is a common complaint among individuals affected by generalised joint hypermobility. In the absence of other conditions that cause chronic pain, these individuals are usually diagnosed with joint hypermobility syndrome (JHS). JHS is a multifactorial trait with a strong genetic basis, but no specific genetic markers. Clinical overlap of JHS is seen with heritable connective tissue disorders, particularly with the Ehlers-Danlos syndrome, hypermobile type (hEDS). The Ehlers-Danlos syndromes (EDS) comprise a heterogeneous group of rare monogenic conditions that are characterised by joint hypermobility, skin and vascular fragility and generalised connective tissue friability, and are caused by genetic defects in an array of extracellular matrix genes...
September 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28949091/new-approach-for-the-treatment-of-neuropathic-pain-fibroblast-growth-factor-1-gene-transfected-adipose-derived-mesenchymal-stem-cells
#13
F Forouzanfar, B Amin, A Ghorbani, H Ghazavi, F Ghasemi, K Sadri, S Mehri, H R Sadeghnia, H Hosseinzadeh
BACKGROUND: Neuropathic pain triggered by peripheral nerve lesion is extremely difficult to manage with current approaches, hence the importance of exploring therapeutic alternatives. METHODS: We have analysed adipose-derived mesenchymal stem cells (AD-MSCs) and fibroblast growth factor 1 gene-transfected adipose-derived mesenchymal stem cells (AD-MSCs (FGF)(1) ) on chronic constriction injury (CCI). The mechanical and thermal hypersensitivity were assessed using the von Frey filament, radiant heat and acetone drop tests...
September 26, 2017: European Journal of Pain: EJP
https://www.readbyqxmd.com/read/28902127/altered-gene-expression-of-rnf34-and-pacap-possibly-involved-in-mechanism-of-exercise-induced-analgesia-for-neuropathic-pain-in-rats
#14
Shintaro Yamaoka, Yusuke Oshima, Hideki Horiuchi, Tadao Morino, Masayuki Hino, Hiromasa Miura, Tadanori Ogata
Despite the availability of several modalities of treatment, including surgery, pharmacological agents, and nerve blocks, neuropathic pain is often unresponsive and sometimes progresses to intractable chronic pain. Although exercise therapy is a candidate for treatment of neuropathic pain, the mechanism underlying its efficacy has not been elucidated. To clarify the molecular mechanism for pain relief induced by exercise, we measured Rnf34 and Pacap mRNA levels in the spinal cord dorsal horn of SNL rats, a model of neuropathic pain...
September 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28868793/chronic-steroid-response-pancytopenia-and-increased-bone-density-due-to-thromboxane-synthase-deficiency
#15
Richa Sharma, Elizabeth Sierra Potchanant, Jennifer E Schwartz, Grzegorz Nalepa
Diagnosis of bone marrow failure (BMF) disorders is challenging but essential for optimal patient management. Here, we report a young adult from nonconsanguineous parents with progressive pancytopenia since childhood, bone pain, increased bone density, and haphazard ossification replacing hematopoiesis within the bone marrow. Sequencing revealed two novel biallelic variants of unknown significance within the thromboxane A synthase gene, TBXAS1 (c.266T > C; c.989T > C), bioinformatically predicted to disrupt the protein...
September 4, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28854965/adipose-stem-cells-from-chronic-pancreatitis-patients-improve-mouse-and-human-islet-survival-and-function
#16
Lili Song, Zhen Sun, Do-Sung Kim, Wenyu Gou, Charlie Strange, Huansheng Dong, Wanxing Cui, Gary Gilkeson, Katherine A Morgan, David B Adams, Hongjun Wang
BACKGROUND: Chronic pancreatitis has surgical options including total pancreatectomy to control pain. To avoid surgical diabetes, the explanted pancreas can have islets harvested and transplanted. Immediately following total pancreatectomy with islet autotransplantation (TP-IAT), many islet cells die due to isolation and transplantation stresses. The percentage of patients remaining insulin free after TP-IAT is therefore low. We determined whether cotransplantation of adipose-derived mesenchymal stem cells (ASCs) from chronic pancreatitis patients (CP-ASCs) would protect islets after transplantation...
August 30, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28822691/fatal-meningitis-in-swine-after-intrathecal-administration-of-adeno-associated-virus-expressing-syngeneic-interleukin-10
#17
Mark D Unger, Josef Pleticha, James E Collins, Anibal G Armien, Jennifer L Brazzell, Laura K Newman, Lukas F Heilmann, Jodi A Scholz, Timothy P Maus, Andreas S Beutler
Interleukin-10 (IL-10) delivered by intrathecal (i.t.) gene vectors is a candidate investigational new drug (IND) for several chronic neurological disorders such as neuropathic pain. We performed a preclinical safety study of IL-10. A syngeneic large animal model was used delivering porcine IL-10 (pIL-10) to the i.t. space in swine by adeno-associated virus serotype 8 (AAV8), a gene vector that was previously found to be nontoxic in the i.t. space. Unexpectedly, animals became ill, developing ataxia, seizures, and an inability to feed and drink, and required euthanasia...
November 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28726577/will-optogenetics-be-used-to-treat-chronic-pain-patients
#18
Hélène Beaudry, Ihab Daou, Alfredo Ribeiro-da-Silva, Philippe Séguéla
Chronic pain affects a third of the population and current treatments produce limited relief and severe side effects. An alternative strategy to decrease pain would be to directly modulate somatosensory pathways using optogenetics. Optogenetics involves the use of genetically encoded and optically active proteins, namely opsins, to control neuronal circuits. In preclinical animal models, optical silencing of peripheral nociceptors has been shown to alleviate both inflammatory and neuropathic pain. An opsin-based gene therapy to treat chronic pain patients is not ready yet, but encouraging advances have been made in optical and viral technology...
July 2017: Pain Management
https://www.readbyqxmd.com/read/28716266/sativex%C3%A2-effects-on-promoter-methylation-and-on-cnr1-cnr2-expression-in-peripheral-blood-mononuclear-cells-of-progressive-multiple-sclerosis-patients
#19
Massimo Santoro, Massimiliano Mirabella, Chiara De Fino, Assunta Bianco, Matteo Lucchini, Francesco Losavio, Andrea Sabino, Viviana Nociti
Multiple sclerosis (MS) is a chronic demyelinating central nervous system (CNS) disease that involve oligodendrocyte loss and failure to remyelinate damaged brain areas causing a progressive neurological disability. Studies in MS mouse model suggest that cannabinoids ameliorate symptoms as spasticity, tremor and pain reducing inflammation via cannabinoid-mediated system. The aim of our study is to investigate the changes in cannabinoid type 1 (CNR1) and 2 (CNR2) receptors mRNA expression levels and promoter methylation in peripheral blood mononuclear cells (PBMCs) of MS secondary progressive (MSS-SP) patients treated with Sativex®...
August 15, 2017: Journal of the Neurological Sciences
https://www.readbyqxmd.com/read/28682314/nasal-application-of-hsv-encoding-human-preproenkephalin-blocks-craniofacial-pain-in-a-rat-model-of-traumatic-brain-injury
#20
A C Meidahl, M Klukinov, A Z Tzabazis, J C Sorensen, D C Yeomans
According to Centers for Disease Control and Prevention, each year, an estimated 1.7 million Americans sustain a traumatic brain injury (TBI), which frequently leads to chronic craniofacial pain. In this study we examine a gene therapy approach to the treatment of post-TBI craniofacial neuropathic pain using nasal application of a herpes simplex virus (HSV)-based vector expressing human proenkephalin (SHPE) to target the trigeminal ganglia. Mild TBI was induced in rats by the use of a modified fluid percussion model...
August 2017: Gene Therapy
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