Phase Ib, Two-centre, Randomised, Observer-blind, Placebo- and Comparator Controlled Trial to Evaluate the Safety, Tolerability and Antipsoriatic Efficacy of Three Strengths of a Topical SPS4251 Formulation in a Psoriasis Plaque Test

The current most important topical treatments for psoriasis are vitamin D3 analogues and/or corticosteroids. The possibility of another effective treatment for psoriasis could be based on the immunosuppressive efficacy of selective blockers of a lymphocyte potassium channel.
The aim of the clinical trial is to evaluate the safety, tolerability and anti-psoriatic efficacy of topical SPS4251 formulations in comparison to placebo and to a marketed topical Vitamin-D analogue ointment in a psoriasis plaque test.

开始日期2013-03-01

申办/合作机构

Circassia Ltd.

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100 项与 SPS-4251 相关的临床结果

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100 项与 SPS-4251 相关的转化医学

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100 项与 SPS-4251 相关的专利（医药）

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项与 SPS-4251 相关的文献（医药）

2023-12-05·Journal of Integrative Neuroscience

Kv1.3 Blockade Alleviates White Matter Injury through Reshaping M1/M2 Phenotypes via the NF-κB Signaling Pathway after Intracerebral Hemorrhage

Article

作者: He, Yijia ; Chen, Jie ; Wang, Shuhong ; Wang, Bo ; Yin, Yi ; Chen, Lin ; Zhong, Jun ; Zuo, Yonglin ; Ge, Hongfei ; Zhang, Chao ; Feng, Hua ; Zhou, Tengyuan ; Zhang, Xuyang

BACKGROUNDWhite matter injury (WMI) in basal ganglia usually induces long-term disability post intracerebral hemorrhage (ICH). Kv1.3 is an ion channel expressed in microglia and induces neuroinflammation after ICH. Here, we investigated the functions and roles of Kv1.3 activation-induced inflammatory response in WMI and the Kv1.3 blockade effect on microglia polarization after ICH.METHODSMice ICH model was constructed by autologous blood injection. The expression of Kv1.3 was measured using immunoblot, real-time quantitative polymerase chain reaction (RT-qPCR), and immunostaining assays. Then, the effect of administration of 5-(4-Phenoxybutoxy) psoralen (PAP-1), a selectively pharmacological Kv1.3 blocker, was investigated using open field test (OFT) and basso mouse score (BMS). RT-qPCR, immunoblot, and enzyme-linked immunosorbent assay (ELISA) were taken to elucidate the expression of pro-inflammatory or anti-inflammatory factors around hematoma. PAP-1's function in regulating microglia polarization was investigated using immunoblot, RT-qPCR, and immunostaining assays. The downstream PAP-1 signaling pathway was determined by RT-qPCR and immunoblot.RESULTSKv1.3 expression was increased in microglia around the hematoma significantly after ICH. PAP-1 markedly improved neurological outcomes and the WMI by reducing pro-inflammatory cytokine accumulation and upregulating anti-inflammatory factors. Mechanistically, PAP-1 reduces NF-κB p65 and p50 activation, thus facilitating microglia polarization into M2-like microglia, which exerts this beneficial effect.CONCLUSIONSPAP-1 reduced pro-inflammatory cytokines accumulation and increased anti-inflammatory factors by facilitating M2-like microglia polarization via the NF-κB signaling pathway. Thus, the current study shows that the Kv1.3 blockade is capable of ameliorating WMI by facilitating M2-like phenotype microglia polarization after ICH.

2023-02-01·Cardiovascular Drugs and Therapy3区 · 医学

Kv1.3 Channel Blockade Improves Inflammatory Profile, Reduces Cardiac Electrical Remodeling, and Prevents Arrhythmia in Type 2 Diabetic Rats

3区 · 医学

Article

作者: Alquiza, Amaia ; Zayas-Arrabal, Julián ; Rodríguez-de-Yurre, Ainhoa ; Casis, Oscar ; Fernández-López, Víctor ; Echeazarra, Leyre ; Gallego, Mónica

AbstractPurposeKv1.3 channel regulates the activity of lymphocytes, macrophages, or adipose tissue and its blockade reduces inflammatory cytokine secretion and improves insulin sensitivity in animals with metabolic syndrome and in genetically obese mice. Thus, Kv1.3 blockade could be a strategy for the treatment of type 2 diabetes. Elevated circulating levels of TNFα and IL-1b mediate the higher susceptibility to cardiac arrhythmia in type 2 diabetic rats. We hypothesized that Kv1.3 channel blockade with the psoralen PAP1 could have immunomodulatory properties that prevent QTc prolongation and reduce the risk of arrhythmia in type 2 diabetic rats.MethodsType 2 diabetes was induced to Sprague-Dawley rats by high-fat diet and streptozotocin injection. Diabetic animals were untreated, treated with metformin, or treated with PAP1 for 4 weeks. Plasma glucose, insulin, cholesterol, triglycerides, and cytokine levels were measured using commercial kits. ECG were recorded weekly, and an arrhythmia-inducing protocol was performed at the end of the experimental period. Action potentials were recorded in isolated ventricular cardiomyocytes.ResultsIn diabetic animals, PAP1 normalized glycaemia, insulin resistance, adiposity, and lipid profile. In addition, PAP1 prevented the diabetes-induced repolarization defects through reducing the secretion of the inflammatory cytokines IL-10, IL-12p70, GM-CSF, IFNγ, and TNFα. Moreover, compared to diabetic untreated and metformin-treated animals, those treated with PAP1 had the lowest risk of developing the life-threatening arrhythmia Torsade de Pointes under cardiac challenge.ConclusionKv1.3 inhibition improves diabetes and diabetes-associated low-grade inflammation and cardiac electrical remodeling, resulting in more protection against cardiac arrhythmia compared to metformin.

2023-02-01·European Journal of Pain

Spinal voltage‐gated potassium channel Kv1.3 contributes to neuropathic pain via the promotion of microglial M1 polarization and activation of the NLRP3 inflammasome

Article

作者: Manyande, Anne ; Gao, Feng ; Yuan, Xiaoman ; Zhang, Wen ; Han, Siyi ; Wang, Jie ; Tian, Xuebi

AbstractBackgroudStudies have shown that the activation of microglia is the main mechanism of neuropathic pain. Kv1.3 channel is a novel therapeutic target for treating neuroinflammatory disorders due to its crucial role in subsets of microglial cells. As such, it may be involved in the processes of neuropathic pain, however, whether Kv1.3 plays a role in neuroinflammation following peripheral nerve injury is unclear.MethodThe spared nerve injury model (SNI) was used to establish neuropathic pain. Western blot and immunofluorescence were used to examine the effect of Kv1.3 in the SNI rats. PAP‐1, a Kv1.3 specific blocker was administered to alleviate neuropathic pain in the SNI rats.ResultsNeuropathic pain and allodynia occurred after SNI, the levels of M1 (CD68, iNos) and M2 (CD206, Arg‐1) phenotypes were up‐regulated in the spinal cord, and the protein levels of NLRP3, caspase‐1 and IL‐1β were also increased. Pharmacological blocking of Kv1.3 with PAP‐1 alleviated hyperpathia induced by SNI. Meanwhile, intrathecal injection of PAP‐1 reduced M1 polarization and decreased NLRP3, caspase‐1 and IL‐1β expressions of protein levels.ConclusionOur research indicates that the Kv1.3 channel in the spinal cord contributes to neuropathic pain by promoting microglial M1 polarization and activating the NLRP3 inflammasome.

项与 SPS-4251 相关的新闻（医药）

2023-12-19

·佰傲谷BioValley

核心管线挫折引发的两次大裁员

拥有全球首款的同种异体T细胞疗法的Atara Biotherapeutics公司如今同样面临现金流的困境。近日（2023年12月18日），Atara将于今年年底裁员近100人，这是上个月公司的一款领先同种异体T细胞疗法Ⅱ期临床失败后，公司进行战略重组的一部分（30%）。截止2023第三季度，Atara净亏损6980万美元，现金流约1.02亿美元，公司预计裁员后其现金流（加上未来其他收入）将支撑公司运营到2025年第三季度。首款上市产品的低期待值Atara成立于2012年，总部位于加州旧金山，由安进与风投机构凯鹏华盈(KPCB)共同出资创建，主要致力于开发肿瘤、自身免疫性疾病和病毒性疾病的同种异体T细胞疗法。Atara的“off-the-shelf”T细胞疗法旨在利用健康人群的PBMCs(人外周血单个核细胞)，经基因改造变为具有精确靶向、适用各类人群的通用型的“off-the-shelf”细胞毒性T细胞。相比较于传统的CAR-T细胞疗法，其具有无需个体化制备、扩增快速等优点。2022年12月19日，Atara的首款T细胞疗法Ebvallo（tabelecleucel）获得了欧盟委员会（EC）批准上市，作为既往接受过至少一种治疗的复发性/难治性EB病毒（EBV）相关的移植后淋巴细胞组织增生性疾病（EBV+PTLD）患者（≥2岁）的单药疗法。这也是全球首款获得监管机构批准的同种异体T细胞疗法。2023年5月，Ebvallo在英国也获得了批准。不过，作为公司的首款上市产品，Ebvallo似乎并没有支撑外界对Atara太多期待。Ebvallo针对的适应症PTLD非常罕见，其发病率约为1%-30%，在美国仅有几百名患者。在一些分析师看来，仅凭目前的适应症，Ebvallo的销售峰值最多可能也就1.4亿美元。Atara自己也坦言，Ebvallo并不会很快成为公司的收入来源，事实上，自获批半年多以来，Ebvallo的销售表现并未掀起太大波澜。由于商业化经验方面不足等问题，Ebvallo在欧洲市场其他选定市场的商业化被Atara移交给了其合作伙伴Pierre Fabre。ATA188引发的两次裁员公司希望寄于在其另一款ATA1在研管线ATA188身上，这也是公司临床进展最快的管线。ATA188是一种同种异体(EBV) T细胞疗法，靶向EBV感染的B细胞和浆细胞，包括中枢神经系统内的细胞和浆细胞。在先前公司报告的临床I期试验中，接受ATA188治疗的进行性多发性硬化症（PMS）患者病情改善了33%。然而推进到II期临床后ATA188就开始变脸。2022年7月13日，一项名为EMBOLD的Ⅱ期临床试验中期分析结果表明，其六个月的数据不足以得出关于ATA188是否会在12个月内带来益处的结论。独立数据和安全监测委员会认为六个月的中期终点可能是对这种干预措施在这种情况下的潜力的不准确衡量。之后不久Atara就做出了裁员20%的决定，裁员总数77人。2023年11月8日，Atara公布了EMBOLD临床最终分析结果，ATA188组患者的残疾改善率为6%，而安慰剂组的改善率为16%，未达到扩展残疾状况量表 (EDSS) 确认残疾改善 (CDI)的临床主要终点目标，试验宣告失败。市场对此反应更为剧烈，Atara股价暴跌80%。Atara总裁兼首席执行官Pascal Touchon表示公司对结果感到惊讶和深感失望。一天后（11月10日），Atara就宣布进行了重组，并表示大幅削减对ATA188的研发支出，将集中资源到其他同种异体CAR-T管线开发上。伴随重组的是30%的裁员计划。参考出处：Atara：明年二季度在美提交首款“现货”T细胞疗法BLAhttps://www.fiercebiotech.com/biotech/atara-stock-plummets-3x-afterhours-following-mystifying-phase-2-data-reviewhttps://www.biospace.com/article/promised-cuts-begin-at-atara-as-77-jobs-on-the-block-/sponse本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处﹀ ········

细胞疗法财报免疫疗法临床2期临床1期

100 项与 SPS-4251 相关的药物交易

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研发状态

10 条进展最快的记录,

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适应症	最高研发状态	国家/地区	公司	日期
银屑病	临床1期	-	Airmid Healthgroup	-
斑块状银屑病	药物发现	德国	Circassia Ltd.	2013-03-01
寻常性银屑病	药物发现	德国	Circassia Ltd.	2013-03-01
特应性皮炎	药物发现	英国	Circassia Ltd.	-