A Phase 2, Proof-of-concept, Multi-center, Randomized, Double-blind, Placebo-controlled Study to Evaluate the Efficacy and Safety of AT-5214 in Subjects with Moderate to Severe Facial Acne Vulgaris

开始日期2024-08-01

申办/合作机构-

NCT04263623 / Unknown status临床2期

A Double-Blind, Randomized, Placebo-Controlled Study to Assess the Efficacy and Safety of AT-5214 in the Treatment of Subjects With Moderate to Severe Palmar Hyperhidrosis

This is a multicenter, randomized, double-blind, placebo-controlled, parallel group comparison study of AT-5214 in subjects with moderate to severe primary palmar hyperhidrosis (sweaty palms). This study will compare two different oral (tablet) doses of AT-5214 (study drug) versus a matched placebo. Approximately 120 subjects will be enrolled at approximately 10 study sites.

开始日期2020-01-31

申办/合作机构

Atacama Therapeutics, Inc.初创企业

NCT03404570 / Completed临床2期

A Double-Blind, Randomized, Placebo-Controlled Exploratory Study to Assess the Efficacy and Safety of TC-5214 in the Treatment of Subjects With Moderate to Severe Palmar Hyperhidrosis

This is a pilot exploratory study to evaluate the safety and efficacy of TC-5214 in subjects with palmar hyperhidrosis.

开始日期2017-12-21

申办/合作机构

Atacama Therapeutics, Inc.初创企业

100 项与 nAChR α4/β2/α5 相关的临床结果

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100 项与 nAChR α4/β2/α5 相关的转化医学

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0 项与 nAChR α4/β2/α5 相关的专利（医药）

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项与 nAChR α4/β2/α5 相关的文献（医药）

2021-01-01·Chemico-Biological Interactions2区 · 医学

E-cigarette aerosols containing nicotine modulate nicotinic acetylcholine receptors and astroglial glutamate transporters in mesocorticolimbic brain regions of chronically exposed mice

2区 · 医学

Article

作者: Hammad, Alaa M ; Alhaddad, Hasan ; Alasmari, Fawaz ; Crotty Alexander, Laura E ; Schiefer, Isaac T ; Moshensky, Alexander ; Shin, John ; Sari, Youssef ; Horton, Austin

Nicotine exposure increases the release of glutamate in part through stimulatory effects on pre-synaptic nicotinic acetylcholine receptors (nAChRs). To assess the impact of chronic electronic (e)-cigarette use on these drug dependence pathways, we exposed C57BL/6 mice to three types of inhalant exposures for 3 months; 1) e-cigarette aerosol generated from liquids containing nicotine (ECN), 2) e-cigarette aerosol generated from liquids containing vehicle chemicals without nicotine (Veh), and 3) air only (AC). We investigated the effects of daily e-cigarette exposure on protein levels of α7 nAChR and α4/β2 nAChR, gene expression and protein levels of astroglial glutamate transporters, including glutamate transporter-1 (GLT-1) and cystine/glutamate antiporter (xCT), in the frontal cortex (FC), striatum (STR) and hippocampus (HIP). We found that chronic inhalation of ECN increased α4/β2 nAChR in all brain regions, and increased α7 nAChR expression in the FC and STR. The total GLT-1 relative mRNA and protein expression were decreased in the STR. Moreover, GLT-1 isoforms (GLT-1a and GLT-1b) were downregulated in the STR in ECN group. However, inhalation of e-cigarette aerosol downregulated xCT expression in STR and HIP compared to AC and Veh groups. ECN group had increased brain-derived neurotrophic factor in the STR compared to control groups. Finally, mass spectrometry detected high concentrations of the nicotine metabolite, cotinine, in the FC and STR in ECN group. This work demonstrates that chronic inhalation of nicotine within e-cigarette aerosols significantly alters the expression of nAChRs and astroglial glutamate transporters in specific mesocorticolimbic brain regions.

2018-10-04·JCI Insight1区 · 医学

Gut microbiota–dependent modulation of innate immunity and lymph node remodeling affects cardiac allograft outcomes

1区 · 医学

ArticleOA

作者: Bromberg, Jonathan S ; Zhang, Tianshu ; Wagner, Chelsea ; Fricke, W Florian ; Li, Lushen ; Simon, Thomas ; Xiong, Yanbao ; Mongodin, Emmanuel F ; Smyth, Eoghan M ; Brinkman, Colin C ; Hittle, Lauren ; Saxena, Vikas

We hypothesized that the gut microbiota influences survival of murine cardiac allografts through modulation of immunity. Antibiotic pretreated mice received vascularized cardiac allografts and fecal microbiota transfer (FMT), along with tacrolimus immunosuppression. FMT source samples were from normal, pregnant (immune suppressed), or spontaneously colitic (inflammation) mice. Bifidobacterium pseudolongum (B. pseudolongum) in pregnant FMT recipients was associated with prolonged allograft survival and lower inflammation and fibrosis, while normal or colitic FMT resulted in inferior survival and worse histology. Transfer of B. pseudolongum alone resulted in reduced inflammation and fibrosis. Stimulation of DC and macrophage lines with B. pseudolongum induced the antiinflammatory cytokine IL-10 and homeostatic chemokine CCL19 but induced lesser amounts of the proinflammatory cytokines TNFα and IL-6. In contrast, LPS and Desulfovibrio desulfuricans (D. desulfuricans), more abundant in colitic FMT, induced a more inflammatory cytokine response. Analysis of mesenteric and peripheral lymph node structure showed that B. pseudolongum gavage resulted in a higher laminin α4/α5 ratio in the lymph node cortical ridge, indicative of a suppressive environment, while D. desulfuricans resulted in a lower laminin α4/α5 ratio, supportive of inflammation. Discrete gut bacterial species alter immunity and may predict graft outcomes through stimulation of myeloid cells and shifts in lymph node structure and permissiveness.

2018-05-01·Cell Chemical Biology1区 · 生物学

A Split-Luciferase-Based Trimer Formation Assay as a High-throughput Screening Platform for Therapeutics in Alport Syndrome

1区 · 生物学

Article

作者: Yokota, Tsubasa ; Motomura, Keishi ; Suico, Mary Ann ; Matsuyama, Shingo ; Kuwazuru, Jun ; Kamura, Misato ; Koyama, Kosuke ; Teramoto, Keisuke ; Fukuda, Ryosuke ; Kai, Hirofumi ; Kaseda, Shota ; Shuto, Tsuyoshi ; Kojima, Haruka ; Omachi, Kohei

Alport syndrome is a hereditary glomerular disease caused by mutation in type IV collagen α3-α5 chains (α3-α5(IV)), which disrupts trimerization, leading to glomerular basement membrane degeneration. Correcting the trimerization of α3/α4/α5 chain is a feasible therapeutic approach, but is hindered by lack of information on the regulation of intracellular α(IV) chain and the absence of high-throughput screening (HTS) platforms to assess α345(IV) trimer formation. Here, we developed sets of split NanoLuc-fusion α345(IV) proteins to monitor α345(IV) trimerization of wild-type and clinically associated mutant α5(IV). The α345(IV) trimer assay, which satisfied the acceptance criteria for HTS, enabled the characterization of intracellular- and secretion-dependent defects of mutant α5(IV). Small interfering RNA-based and chemical screening targeting the ER identified several chemical chaperones that have potential to promote α345(IV) trimer formation. This split luciferase-based trimer formation assay is a functional HTS platform that realizes the feasibility of targeting α345(IV) trimers to treat Alport syndrome.