An Open-label, Randomized, Multiple-dose, Crossover Study to Evaluate the Pharmacokinetics/ Pharmacodynamics and Safety of DA-4001 in Healthy Male Subjects with Androgenic Alopecia.

开始日期2016-07-01

申办/合作机构

Dong-A ST Co., Ltd.

100 项与 VGKCs x 5α-reductase x Potassium channel 相关的临床结果

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100 项与 VGKCs x 5α-reductase x Potassium channel 相关的转化医学

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0 项与 VGKCs x 5α-reductase x Potassium channel 相关的专利（医药）

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项与 VGKCs x 5α-reductase x Potassium channel 相关的文献（医药）

2022-04-14·European Heart Journal1区 · 医学

Evaluation of gene validity for CPVT and short QT syndrome in sudden arrhythmic death

1区 · 医学

Article

作者: Novelli, Valeria ; Walsh, Roddy ; Trevisan, Valentina ; Abiusi, Emanuela ; Amenta, Simona ; Nannenberg, Eline A ; Feilotter, Harriet ; Hershberger, Ray E ; Bikker, Hennie ; Amin, Ahmad S ; Mazzarotto, Francesco ; Garcia, John ; Gollob, Michael H ; Wilde, Arthur A M ; Adler, Arnon ; Perez, Marco V ; Care, Melanie ; Zareba, Wojciech ; Sturm, Amy C ; Ware, James S

AbstractAimsCatecholaminergic polymorphic ventricular tachycardia (CPVT) and short QT syndrome (SQTS) are inherited arrhythmogenic disorders that can cause sudden death. Numerous genes have been reported to cause these conditions, but evidence supporting these gene–disease relationships varies considerably. To ensure appropriate utilization of genetic information for CPVT and SQTS patients, we applied an evidence-based reappraisal of previously reported genes.Methods and resultsThree teams independently curated all published evidence for 11 CPVT and 9 SQTS implicated genes using the ClinGen gene curation framework. The results were reviewed by a Channelopathy Expert Panel who provided the final classifications. Seven genes had definitive to moderate evidence for disease causation in CPVT, with either autosomal dominant (RYR2, CALM1, CALM2, CALM3) or autosomal recessive (CASQ2, TRDN, TECRL) inheritance. Three of the four disputed genes for CPVT (KCNJ2, PKP2, SCN5A) were deemed by the Expert Panel to be reported for phenotypes that were not representative of CPVT, while reported variants in a fourth gene (ANK2) were too common in the population to be disease-causing. For SQTS, only one gene (KCNH2) was classified as definitive, with three others (KCNQ1, KCNJ2, SLC4A3) having strong to moderate evidence. The majority of genetic evidence for SQTS genes was derived from very few variants (five in KCNJ2, two in KCNH2, one in KCNQ1/SLC4A3).ConclusionsSeven CPVT and four SQTS genes have valid evidence for disease causation and should be included in genetic testing panels. Additional genes associated with conditions that may mimic clinical features of CPVT/SQTS have potential utility for differential diagnosis.

2018-11-01·Molecular Nutrition & Food Research2区 · 农林科学

Maternal Red Blood Cell Folate and Infant Vitamin B₁₂ Status Influence Methylation of Genes Associated with Childhood Acute Lymphoblastic Leukemia

2区 · 农林科学

Article

作者: Relton, Caroline Laura ; Mathers, John Cummings ; MKay, Jill Ann ; Strathdee, Gordon ; Moorman, Anthony Vincent ; Ford, Dianne ; Potter, Catherine

ScopeInadequate maternal folate intake is associated with increased childhood acute lymphoblastic leukemia (ALL) risk. Folate provides methyl groups for DNA methylation, which is dramatically disrupted in ALL. Whether or not maternal folate (and related B‐vitamin) intake during pregnancy may affect ALL risk via influencing DNA methylation is investigated.Methods and ResultsGenes in which methylation changes are reported both in response to folate status and in ALL are investigated. Folate‐responsive genes (n = 526) are identified from mouse models of maternal folate depletion during pregnancy. Using published data, 2621 genes with persistently altered methylation in ALL are identified. Overall 25 overlapping genes are found, with the same directional methylation change in response to folate depletion and in ALL. Hypermethylation of a subset of genes (ASCL2, KCNA1, SH3GL3, SRD5A2) in ALL is confirmed by measuring 20 patient samples using pyrosequencing. In a nested cohort of cord blood samples (n = 148), SH3GL3 methylation is inversely related to maternal RBC folate concentrations (p = 0.008). Furthermore, ASCL2 methylation is inversely related to infant vitamin B12 levels. (p = 0.016).ConclusionFindings demonstrate proof of concept for a plausible mechanism, i.e., variation in DNA methylation, by which low intake of folate, and related B‐vitamins during pregnancy may influence ALL risk.

2016-12-01·Psychoneuroendocrinology2区 · 医学

Exploring the neural mechanisms of finasteride: a proteomic analysis in the nucleus accumbens

2区 · 医学

Article

作者: Calzetta, Luigino ; Piras, Cristian ; Urbani, Andrea ; Soggiu, Alessio ; Roncada, Paola ; Devoto, Paola ; Greco, Viviana ; Bortolato, Marco

The enzyme 5α-reductase (5αR) catalyzes the conversion of progesterone and testosterone into neuroactive steroids implicated in a wide array of behavioral functions. The prototypical 5αR inhibitor, finasteride (FIN), is clinically approved for the treatment of androgenic alopecia and benign prostatic hyperplasia. Recent evidence has shown that FIN, albeit generally well tolerated, can induce untoward psychological effects in a subset of patients; furthermore, this drug may have therapeutic efficacy for a number of different neuropsychiatric conditions, ranging from Tourette syndrome to schizophrenia. In rat models of these conditions, FIN has been shown to block the effects of dopamine receptors in the nucleus accumbens (NAcc), a key terminal of the dopamine mesolimbic system. The biological underpinnings of these effects, however, remain mostly elusive. To elucidate the neurochemical networks that may be responsible for the behavioral effects of FIN, we evaluated the proteomic profile of the NAcc following acute (100mg/kg, IP) and subchronic (7 days; 100mg/kg/day, IP) treatment with this drug, in comparison with vehicle treatment (n=5/group). Two-dimensional electrophoresis (2-DE) analysis coupled to mass spectrometry revealed significant changes in the expression of nine proteins (CRMP2, PSMD1, STX18, KCNC3, CYP255, GABRP, GABT, PRPS1, CYP2B3), which were further analyzed by ontological classification (PANTHER). These results point to a number of novel potential chemical targets of FIN, and may help elucidate the underpinnings of FIN's behavioral effects and therapeutic potential for neuropsychiatric disorders.