STEM-PD Trial: A Multicentre, Single Arm, First in Human, Dose-escalation Trial, Investigating the Safety and Tolerability of Intraputamenal Transplantation of Human Embryonic Stem Cell Derived Dopaminergic Cells for Parkinson's Disease (STEM-PD Product)

Parkinson's disease (PD) occurs when an area of the brain begins to lose nerve cells that produce a chemical called dopamine. Dopamine is an important chemical, and one of its functions is that it helps to regulate body movement. The loss of these nerve cells leads to a reduction of dopamine in the brain. Medications used to treat PD temporarily replace this lost dopamine, but they do not repair the underlying disease. One of the most promising PD therapies to date has been the transplantation of dopamine producing cells into the brain. Unlike current treatments, these therapies may be able to repair the damage caused in PD.
In this trial, the investigators will transplant a new stem cell therapy, called the STEM-PD product, into the area of the brain affected in people with PD. These stem cells can develop into many different cell types, including dopamine-producing nerve cells. The investigators will transplant the stem cells using a device that has been previously used for similar transplants in Lund. This is the first time that the STEM-PD product will be given to humans.
The trial aims to assess whether the STEM-PD product is safe to use in people with PD. The investigators will also be looking for preliminary signs of efficacy.
The trial will recruit participants with PD from the UK and Sweden. Eight participants will undergo the STEM-PD product transplant. Participants will receive a single dose of the STEM-PD product. Participants will attend for 25 visits primarily at their local recruiting hospital. For participants from the UK, some of the imaging will be performed at Invicro (London), and the surgery (including some visits before and after) and some imaging will be performed in Lund. All participants will be followed up for 36 months following surgery

开始日期2022-11-30

申办/合作机构

Region Skåne Holding AB

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100 项与 STEM-PD 相关的临床结果

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100 项与 STEM-PD 相关的转化医学

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100 项与 STEM-PD 相关的专利（医药）

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项与 STEM-PD 相关的文献（医药）

2018-05-04·Journal of Animal Science2区 · 农林科学

Supplementation of Bacillus subtilis-based probiotic reduces heat stress-related behaviors and inflammatory response in broiler chickens1

2区 · 农林科学

Article

作者: Yan, F F ; Amen, O A ; Hu, J Y ; Cheng, H W ; Wang, W C

Probiotics reduce stress-related inflammation and abnormal behaviors in humans and rodents via regulation of the microbiota-gut-brain axis. The objective of this study was to determine if probiotic, Bacillus subtilis, has similar functions in broiler chickens under heat stress (HS). Two hundred forty 1-d-old broiler chicks were assigned to 48 pens with 4 treatments: Thermoneutral (TN)-RD (regular diet), TN-PD (the regular diet mixed with 1 × 106 CFU/g feed probiotic), HS-RD and HS-PD. Probiotic (Sporulin) was fed from day 1; and HS at 32°C for 10 h daily was initiated at day 15. The data showed that final BW, average daily gain , and feed conversion efficiency were improved in PD groups as compared to RD groups regardless of the ambient temperature (P < 0.01). Heterophil to lymphocyte ratio was affected by treatment and its value was in the order of HS-RD > HS-PD > TN-RD > TN-PD birds (P < 0.01). Compared to TN birds, HS birds spent more time in wing spreading, panting, squatting close to the ground, drinking, sleeping, dozing, and sitting but spent less time in eating, standing, and walking (P < 0.05 or 0.01). In addition, HS birds had greater levels of hepatic IL-6, IL-10, heat shock protein (HSP)70, and HSP70 mRNA expression (P < 0.01) and greater levels of cecal IgA and IgY (P < 0.01) compared to TN birds. Within TN groups, TN-PD birds had greater concentrations of hepatic IL-10 (P < 0.05) and cecal IgA (P < 0.01) than TN-RD birds. Within HS groups, HS-PD birds spent less time in wing spreading, panting, squatting close to the ground, drinking, sleeping, dozing, and sitting but spent more time in eating, foraging, standing, and walking than HS-RD birds (P < 0.05 or 0.01). The HS-PD birds also had lower concentrations of hepatic IL-6 and HSP70 (P < 0.01), whereas greater levels of IL-10 (P < 0.05) and lower concentrations of cecal IgA and IgY (P < 0.01). These results indicate that broilers fed the probiotic, B. subtilis, are able to cope with HS more effectively by ameliorating heat-induced behavioral and inflammatory reactions through regulation of microbiota-modulated immunity.

2017-11-01·Parkinsonism & Related Disorders3区 · 医学

Depression may negatively affect the change in freezing of gait following subthalamic nucleus stimulation in Parkinson's disease

3区 · 医学

Article

作者: Jeon, Beomseok ; Kim, Ryul ; Kim, Aryun ; Paek, Sun Ha ; Kim, Ah-Ro ; Kim, Yoon ; Kim, Han-Joon ; Shin, Chae-Won

OBJECTIVETo assess the influence of preoperative depression on the change in freezing of gait (FOG) following subthalamic nucleus stimulation (STN-DBS) in patients with Parkinson's disease (PD).METHODSOne hundred and twelve PD patients were included who received bilateral STN-DBS. Of these, 33 had no preoperative depression (PD-ND) and the other 79 had preoperative depression (PD-D). Each PD-ND patient was matched with one PD-D patient by the propensity score for which sex, age at PD onset, disease duration, UPDRS-III score during off-medication state, levodopa-equivalent daily dose, and mini mental state examination were the independent variables. We compared both a FOG-questionnaire (FOG-Q) and the axial score from UPDRS-III between the two groups over 12-month follow-up.RESULTSDuring the off-medication state, FOG-Q at 12-month was decreased with STN-DBS in both PD-ND (-52.9%, p < 0.001) and PD-D (-24.2%, p < 0.001) with a significant difference in the change of FOG in favor of PD-ND (p = 0.001). Similarly, there was an improvement in the axial score for both PD-ND (-66.1%, p < 0.001) and PD-D (-45.3%, p < 0.001) at 12-month with a significant difference between the groups. (p = 0.005). During the on-medication state, both the FOG-Q and axial score at 12-month were not improved with STN-DBS in the PD-ND and PD-D with no difference between the groups.CONCLUSIONSOur findings suggest that preoperative depression negatively affects the outcome of FOG following STN-DBS in the off-medication state but not in the on-medication state.

2007-02-01·Journal of Lipid Research2区 · 生物学

Inhibition of lipase activities by basic polysaccharide

2区 · 生物学

Article

作者: Hiroe Takaichi ; Toshiya Sawai ; Takahiro Tsujita ; Jun Hiraki ; Takeshi Takaku ; Naoyuki Yoshida

Basic polysaccharide strongly inhibited the hydrolysis of trioleoylglycerol (TO) emulsified with phosphatidylcholine and taurocholate by either pancreatic lipase or carboxylester lipase. DEAE-Sephadex dose-dependently inhibited the hydrolysis of TO by pancreatic lipase and carboxylester lipase; however, carboxymethyl-Sephadex and Sephadex G-50 did not inhibit the hydrolysis. Polydextrose (PD), a soluble polysaccharide, was a very weak inhibitor of pancreatic lipase. However, when a basic group, a DEAE group, was attached to PD, lipase inhibition by DEAE-PD was increased, and this was dependent on the substitution ratio of DEAE groups. The number of positive charges per PD molecule is important in lipase inhibition. Similar substitution effects were observed with other basic groups, such as piperidinoethyl and 3-triethylamino-2-hydroxypropyl. The natural basic polysaccharide, chitosan, also inhibited pancreatic lipase activity. Gel-filtration experiments suggested that DEAE-PD did not bind strongly to pancreatic lipase. The effect of DEAE-PD on TO hydrolysis by pancreatic lipase was studied using various emulsifiers: DEAE-PD (50 microg/ml) did not inhibit the hydrolysis of TO emulsified with arabic gum, phosphatidylserine, or phosphatidic acid. In vivo, oral administration of DEAE-PD to rats reduced the peak plasma triacylglycerol concentration and increased fecal lipid excretion. These results suggest that basic polysaccharide is able to suppress dietary fat absorption from the small intestine by inhibiting pancreatic lipase activity.

项与 STEM-PD 相关的新闻（医药）

2023-08-15

·生物制品圈

首款BCMA-ADC，美国退市1年后国内启动III期临床，Blenrep或将以联合疗法方式重返市场

近日，葛兰素史克（GSK）ADC药物Blenrep，在国内启动了一项III期临床。用于治疗在复发性/难治性多发性骨髓瘤。Blenrep由人源化抗 B 细胞成熟抗原（BCMA）单克隆抗体和细胞毒药物澳瑞他汀 F（auristatinF），通过不可切割的连接子偶联而成。该药物靶向BCMA，这是一种在浆细胞的存活中起重要作用的细胞表面蛋白，并在多发性骨髓瘤细胞中表达。作为全球首个靶向BCMA的ADC疗法，Blenrep于2020年获得FDA的加速批准。BCMA为靶点的MM免疫疗法（来源文献PMID：31277554）单药治疗先前接受过至少四种疗法（包括抗CD38单抗、蛋白酶体抑制剂和免疫调节剂）的成年复发或难治性多发性骨髓瘤（RRMM）患者。BlenrepBlenrep（Belantamab、玛贝妥单抗）是葛兰素史克研发的一款靶向B细胞成熟抗原（BCMA）的抗体药物偶联物（ADC）.作为世界首个个被批准的抗BCMA（B细胞成熟抗原）疗法，于2020年获得美国食品和药物管理局（FDA）批准上市。抗体：人源化抗B细胞成熟抗原（BCMA）单抗；细胞毒素：微管抑制剂单甲基auristatin-F（MMAF）；连接子：不可切割的半胱氨酸残基的抗蛋白酶马来酰亚胺己酰基（MC）靶点：BCMA 适应症：先前已接受过至少4种疗法（包括一种抗CD38抗体、一种蛋白酶体抑制剂、一种免疫调节剂）的复发或难治性多发性骨髓瘤（MM）成人患者。Blenrep（Belantamab）可通过MMAF诱导的细胞凋亡以及通过抗体依赖性细胞毒性（ADCC）和抗体依赖性细胞吞噬作用（ADCP）介导的肿瘤细胞裂解，介导肿瘤细胞的杀伤。BCMA靶点BCMA（TNFRSF17或CD269）是TNF受体超家族17的成员，是MM新药研发的热门靶点。在晚期B淋巴细胞和恶性浆细胞表面高表达，在造血干细胞上表达水平低，在非造血细胞中无表达。belantamab mafodotin作用机制（来源于文献PMID:31859245）美国退市2022年，Blenrep落地海南博鳌乐城，被引入中国。然而同年11月，葛兰素史克宣布，在关于RRMM的III期试验DREAMM-3中，没有达到无进展生存期（PFS）主要终点。这是一项开放标签、随机、头对头、优势3期试验，评估了Blenrep单药治疗、泊马度胺联合低剂量地塞米松（PomDex）的疗效和安全性。葛兰素史克宣布停止在美国销售其血癌药物Blenrep，但将继续该药物的试验计划，一些患者将可以选择报名继续使用该疗法。Blenrep在国内启动III期临床，联合泊马度胺与地塞米松方案（B-Pd）相比泊马度胺加硼替佐米与地塞米松方案（PVd）治疗在复发性/难治性多发性骨髓瘤受试者的有效性和安全性的III期、多中心、开放性、随机研究（DREAMM-8）。或许未来，Blenrep将以联合用药方式，重返市场。

临床3期抗体药物偶联物免疫疗法临床结果

2023-08-11

·生物制药小编

在美退市ADC积极转向国内市场

葛兰素史克（GSK）在美国退市ADC药物Blenrep近日在国内启动了一项III期临床，联合泊马度胺与地塞米松方案（B-Pd）相比泊马度胺加硼替佐米与地塞米松方案（PVd）治疗在复发性/难治性多发性骨髓瘤受试者的有效性和安全性的III期、多中心、开放性、随机研究（DREAMM-8）。验证性Ⅲ期临床失败，Blenrep火速退市Belantamab mafodotin为GSK和Seagen合作开发的一款BCMA-ADC药物，抗体部分为人源化抗B细胞成熟抗原（BCMA）单抗，细胞毒药物为微管抑制剂单甲基auristatin-F（MMAF），连接子为不可切割的半胱氨酸残基的抗蛋白酶马来酰亚胺己酰基（MC）。Blenrep是首款获得FDA批准上市的BCMA靶向药，2020年8月5日，基于一项DREAMM-2临床研究6个月的随访数据，Blenrep获得FDA加速批准上市，作为R/RMM患者的四线疗法。虽然Blenrep拥有进入市场的先发优势，但疗效相对一般，远不及后面获批的两款BCMA-CAR-T以及BCMA/CD3双抗。并且在对其申请上市数据进行审查时，还有一个令FDA担忧的副作用--眼毒性，在DREAM-2的Ⅱ期临床中，有40%接受Blenrep治疗的患者出现3级以上的眼毒性副作用。因此在一获得批准上市的同时，Blenrep也附带了一个关于眼部毒性的黑框警告，包括严重的视力丧失。由于Blenrep是通过加速批准的途径获得批准上市的，上市后需要继续进行验证性临床试验结果来决定是转为完全批准还是做撤回批准处理。2022年11月7日，Blenrep的验证性III期临床DREAMM-3试验宣告失败，无进展生存期 (PFS) 的主要终点未能达到。与对照组相比，虽然Blenrep组的mPFS更长（11.2个月 VS 7个月），但不显著。Blenrep组与对照组ORR分别为41%和36%；12个月DOR率分别为76.8%和48.4%，中位DOR未达到；安全性方面与此前所报告的一致，没有发现新的安全性信号。这个临床结果公布的15天后，葛兰素史克应FDA要求，迅速宣布将该药物撤出美国市场。Blenrep也是自“加速批准”政策成立以来，最快实现退市的药物。在美退市后，葛兰素史克并没有因此彻底放弃Blenrep，Blenrep在其他已获得批准的国家（欧盟）中仍在继续销售。另外公司也将继续推进其他DREAMM临床试验以及在其他国家的上市。而Blenrep的重新上市的希望也依托于DREAMM-7（NCT04246047）和DREAMM-8（NCT04484623）两项Ⅲ期临床结果。其中DREAMM-7旨在评估【Blenrep+硼替佐米+地塞米松】对比【daratumumab+硼替佐米+地塞米松】的安全性和有效性。DREAMM-8—评估【Blenrep+泊马度胺+地塞米松】对比【硼替佐米+泊马度胺+地塞米松】治疗R/RMM的安全性和有效性。公司在公告中曾披露，这两项Ⅲ临床试验初步结果计划是在今年上半年公布，如今看来并未如期披露。Blenrep是在2020年5月在国内获得了临床批准，联合硼替佐米和地塞米松用于二线治疗MM的二线治疗。2022年5月，Blenrep还作为特许药械落地中国海南博鳌超级医院，并被纳入乐城全球特药险。总结作为是目前唯一坚持到上市的BCMA-ADC，Blenrep在MM中地位已然不如上市之初，如果通过剂量调整在后续临床中取得疗效支撑，未来仍有重返市场的可能，但更大概率是作为一种联合用药手段。参考出处：https://xqimg.imedao.com/189cad2b06ae0d073fef722a.png!raw.jpg

临床3期临床2期加速审批上市批准抗体药物偶联物

100 项与 STEM-PD 相关的药物交易

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