Background
Adults over the age of 60 with symptoms of major depressive disorder are said to have late-life depression (LLD), a condition that usually decreases a person's quality of life and is associated with other risks like physical frailty and dementia. A common feature of more severe LLD is psychomotor slowing, where a person's ability to think and move are impaired. For example, they might not be able to walk or process information as quickly, and they might have problems with their working memory.
Psychomotor slowing in LLD might be the result of a problem with the way a person's body produces or responds to the neurotransmitter dopamine. The drug Levodopa (L-DOPA), which can replace missing dopamine in the brain, has been used to treat to treat Parkinson's disease for many decades, and it might also affect psychomotor slowing in LLD.
Methods
In this study, participants are adults aged 60 years or older with moderate to severe major depression. Participants undergo the "L-DOPA challenge"-a 2-week period where they receive a dose of L-DOPA once a day for the first week and a dose of L-DOPA twice a day for the second week. Before and after a participant completes the L-DOPA challenge, the study team assesses their depressive symptoms and psychomotor function. After the L-DOPA challenge, if a participant still shows signs of moderate or severe depression, they receive an antidepressant for 12 weeks.
Aims
The first aim of this study is to test the feasibility of the L-DOPA challenge-that is, whether most of the 50 participants recruited for this study will complete the L-DOPA challenge. For example, participants might have to withdraw if they can't make the daily visits to the research site to receive their L-DOPA medication, if they can't tolerate the medication's side effects, or if their depressive symptoms get significantly worse. Our hypothesis is that 80% of the participants will complete the L-DOPA challenge.
The second aim of the study is to see if L-DOPA affects participants' depressive symptoms, processing speed, and working memory. Our hypothesis is that L-DOPA response, measured as an improvement in gait speed, is associated with a decrease in depressive symptoms and an increase in processing speed and working memory.

开始日期2024-08-15

申办/合作机构

University of British Columbia

[+1]

NCT06365515

/ RecruitingN/AIIT

Dopamine and Reward Learning Across Hormonal Transition Phases

Hormonal transition periods during the menstrual cycle may predispose women to mental disorders. Hormonal fluctuations provide specific neuroendocrine conditions that modulate brain structure and function and these actions affect cognitive and emotional behaviors and affect energy and mood homeostasis. It is thought that these changes are driven by altered dopamine transmission. Here, the investigators aim to examine (1) how sex hormones and dopamine are linked and also (2) how hormonal changes affect motivation, mood, and energy homeostasis.
To this end, dopamine intervention will be tested on effort-based decision-making and motivational circuits in three hormonal stages (i.e., women in early-follicular phase (EF), women in mid-luteal phase (ML), and men). Additionally, the effects of hormonal status on metabolic indices will be tested, and its effects on mood fluctuations in a period of a month.
The investigator hypothesizes that women in EF cycle phase (1) have naturally less dopamine and show less effort, and (2) they show greater improvement in effort-based decision-making after Levodopa administration. The investigator has exploratory outcomes about (3) sex differences in reward-learning with and without Levodopa administration and explores if these differences correlate with elevated female sex hormone levels. Moreover, it is hypothesized that (4) hormonal fluctuations affect energy homeostasis, thus women in their EF cycle phase have higher energy expenditure and (5) they report more negative mood than in their mid-luteal (ML) cycle phase.

开始日期2024-05-01

申办/合作机构

Deutsche Forschungsgemeinschaft

[+1]

JPRN-UMIN000054201

/ RecruitingN/A

Low-dose L-DOPA treatment for drug-induced dystonia - Low-dose L-DOPA treatment for drug-induced dystonia

开始日期2024-04-18

申办/合作机构

Osaka Neurological Institute

100 项与左旋多巴相关的临床结果

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100 项与左旋多巴相关的转化医学

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100 项与左旋多巴相关的专利（医药）

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38,166

项与左旋多巴相关的文献（医药）

2025-11-01·Talanta

Dual enzyme-mimicking bimetallic MOF for selective SERS detection of L-DOPA in human serum based on cascade catalytic reaction

Article

作者: Chen, Ying ; Cheng, Xingliang ; Li, Gongke ; Hu, Yuling ; Liu, Shuojiang

Surface-enhanced Raman scattering (SERS) in conjunction with nanozymes has emerged as a powerful technique for bioanalysis due to their signal conversion and amplification effect. However, clinical applications continue to encounter challenges such as inadequate selectivity. Herein, we proposed a novel approach for the selective SERS detection of L-DOPA in human serum with dual enzyme-mimicking MOF-919(Fe-Cu). This material exhibits both catechol oxidase-like and peroxidase-like activities, enabling it to catalyze catecholic compounds to o-quinones and subsequently oxidize 3,3',5,5'-tetramethylbenzidine (TMB) molecules into SERS-active ox-TMB. Ultrasonic-assisted synthesis ensures uniform and dense loading of AgNPs within MOF-919(Fe-Cu), thereby enhancing SERS activity. A sensitive and selective method for SERS detection of L-DOPA was developed. The catechol oxidase-like activity of MOF-919(Fe-Cu) provides ideal selectivity and anti-interference to L-DOPA, while the cascade catalytic system transforms weak SERS signals of L-DOPA into amplified SERS signals of ox-TMB. The mechanism of dual enzyme-mimicking activity was further discussed. The detection process was optimized to achieve high sensitivity towards L-DOPA with a linear range 0.5-100 μmol/L and low limit of detection (LOD) of 0.16 μmol/L. Furthermore, it has been applied in serum sample of Parkinson's patients, demonstrating excellent recovery and low relative error compared to HPLC-UV. This approach offers an economical, efficient and accurate strategy for the detection of L-DOPA and provides valuable insights for the integration of selective multifunctional nanozyme and sensitive SERS detection method.

2025-09-01·Journal of Environmental Sciences

Long-term cadmium stress influenced the immune response of Pardosa pseudoannulata by modulating its gut microbiota and hemolymph metabolome

Article

作者: Peng, Yuan-de ; She, Qingling ; Zhou, Rong ; Peng, Jie ; Yang, Xinyi ; Wang, Juan ; Li, Jinjin ; Song, Qisheng ; Wang, Zhi

Cadmium (Cd) is a common environmental heavy metal pollutant known for its toxic effects on various plants and animals. Cd contamination also poses a threat to Pardosa pseudoannulata, a predator in rice paddies. Results indicate that Cd pollution significantly reduced the levels of Metallothionein, phenoloxidase, and Ca²⁺. Furthermore, through metabolomics and 16S rDNA sequencing, alterations in the gut microbiota and immune-related metabolites of P. pseudoannulata were identified. The abundance of harmful bacteria such as Staphylococcus increased significantly, while levels of l-Tyrosine, glutathione disulfide, l-Dopa, among others, decreased markedly. Pearson correlation analysis revealed significant associations between various gut microbes and immune-related metabolites, suggesting that Cd may alter the immune system of P. pseudoannulata by modulating its gut microbiota.

2025-07-01·Phytomedicine

Integrated network pharmacology, metabolomics, and microbiome studies to reveal the therapeutic effects of Anacyclus pyrethrum in PD–MCI mice

Article

作者: Shataer, Samire ; Wu, Qin Fen ; Ma, Liang Ying ; Shan Li, Pei ; Chen, Yan ; Tuersong, Tayier ; Shataer, Munire ; Yong, Yu Xuan ; Yang, Xin Ling

BACKGROUNDAnacyclus pyrethrum (l.) DC has potential value in treating Parkinson's disease (PD)-mild cognitive impairment (MCI), manifesting as impaired memory, attention, executive function, and language. However, the specific targets and modes of action of A. pyrethrum remain unclear.PURPOSEThe aim of this study was to identify the active components of A. pyrethrum and examine their effectiveness in treating a mouse model of PD-MCI.METHODSWe generated ethanol extracts of A. pyrethrum root (EEAP) and identified its active components and related targets using UHPLC-MS/MS and network pharmacology.The PD-MCI model was induced via intraperitoneal administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP). After following continuous administration of EEAP,Altered learning or memory, as well as anxiety, were tested using the morris water maze, eight-arm radial arm maze (RAM), and open-field test,elevated plus-maze. Brain histopathology and ultrastructural changes were examined using brightfield microscopy, and electron microscopy, respectively. Furthermore, protein expression was assessed using western blotting.Stool samples were used for metabolomics analysis by UHPLC-MS/MS and for 16S rDNA sequencing to determine the compositional changes of the gut microbiota.We conducted a short-chain fatty acid targeted metabolomics experiment to study their role in the gut-brain axis in PD-MCI.RESULTSUsing UPLC-MS-MS, 126 compounds were identified from A. pyrethrum samples.After searching the databases and literature reports, 31 active components and 544 drug-disease targets were screened. Biological processes and molecular functions, such as energy channels, cell signaling, and metabolism, were discovered through GO analysis. The water maze experiment showed that the average swimming distance and escape latency of mice in EEAP groups decreased. The eight-arm maze experiment showed that model had a much higher number of errors related to working memory than the control mice. In the open field experiment, compared with the control group, the mice in the EEAP group exhibited an increase in the average movement speed and total movement distance, along with a decrease in the residence time.In the elevated plus maze, the control had less anxiety than the Model. Donepezil/Levodopa(D/l) mitigated anxiety-like behavior, and EEAP (100-400 mg/kg) showed a dose-dependent increase in open-arm metrics, suggesting it may ease anxiety in mice.Hippocampal tissue of mice treated with different doses of EEAP showed intact cellular layers and the hematoxylin-eosin-stained cones were slightly better;cells were arranged neatly; their morphology was normal, and were distributed uniformly. Electron microscopy revealed that the nuclear membrane, chromatin, and nucleoli were clearly demarcated in the hippocampus of mice treated with different doses of EEAP, contrary to that in the model group. In brain extracts of the EEAP group, lighter thinner bands for amyloid precursor protein (APP) and Aβ were observed compared to those in the model group. In model mice, APP and Aβ protein expression was higher than in the blank group, as shown by stronger bands. In EEAP-treated mice, the bands were weaker, indicating reduced expression. In the model group had lower Bcl-2 and higher Bax levels. EEAP treatment increased Bcl-2 and decreased Bax expression.Compared to the control group, the model showed substantially low glutathione peroxidase (GSH-Px),superoxide dismutase(SOD),catalase (CAT)activity (p < 0.05),much higher (p < 0.05) in the EEAP-H group than that in the model. EEAP intervention significantly modulated the fecal metabolic profile of PD-MCI mice. The abundance of steroid and lipid metabolites, including linoleylethanolamine, was markedly altered in the model group compared to the control group, with EEAP treatment reversing several of these abnormalities. PLS-DA and OPLS-DA revealed significant separation between groups (Q2= 0.542, p < 0.01), confirming a dose-dependent effect. Random forest analysis identified 15 key metabolic markers, such as dose-dependent changes in d-glutamine and hydrocodone. Metabolic pathway analysis demonstrated significant enrichment in phenylalanine, tyrosine, tryptophan metabolism, and arginine biosynthesis pathways (p < 0.05). The Support Vector Machine (SVM) model achieved an AUC approaching 1, indicating substantial differences in metabolite profiles. EEAP intervention significantly influenced the composition and functional profile of the intestinal microbiota. The Venn diagram illustrates that each group shared 342 operational taxonomic units (OTUs), with the EEAP 400 group exhibiting a distinct Bacteroidetes proportion. LEfSe analysis identified g_Prevotella as the characteristic bacterium in the control group, c_Epsilonproteobacteria in the model group, and g_Adlercreutzia in the EEAP 100 group. The Faith's Phylogenetic Diversity (PD) index was highest in the EEAP 100 group, and Non-metric Multidimensional Scaling (NMDS)/Principal Coordinates Analysis (PCoA) revealed significant differences in microbial community structure. Short-chain fatty acids (SCFAs) analysis indicated that acetic acid was the predominant metabolite, while EEAP dose-dependently regulated propionic acid and isovaleric acid levels (VIP > 1, p < 0.001). These findings demonstrate that EEAP exerts its regulatory effects by reshaping the structure and metabolic functions of the gut microbiota.CONCLUSIONEEAP holds great promise as a potential therapeutic agent for PD-MCI, exerting its effects through multiple mechanisms, including regulating protein expression, modulating the fecal metabolic profile, and reshaping the gut microbiota and its metabolites.

667

项与左旋多巴相关的新闻（医药）

2025-05-04

·生物探索

Nature Biotechnology | 失败也是财富：TransEuro试验如何为下一代帕金森疗法“趟雷”？

引言想象一下，如果大脑里那些掌控你每一个动作的“芯片”突然坏掉，让你无法自如地行走、说话、甚至写字，生活被一点点剥夺……这就是帕金森病（Parkinson's disease, PD）患者面临的残酷现实。这种疾病的核心，在于大脑深处那些制造多巴胺（dopamine）的关键神经元死了，多巴胺就像大脑的“燃料”，没了它，运动系统就陷入了困境。多年来，研究人员一直怀揣着一个大胆的梦想：既然神经元坏死了，能不能直接“种”一些新的进去，像修复电路一样，让大脑重新运转起来？人类胎儿腹侧中脑组织（human fetal ventral mesencephalic tissue, hfVM）中含有多巴胺神经前体细胞，被认为是“修补大脑”的希望之源。早期的移植尝试，有过令人惊叹的成功案例，病人重获新生；但也留下了失败的阴影，甚至带来了无法预期的副作用，让这项技术充满了争议和不确定性。在这种希望与挑战并存的背景下，一项备受关注的欧洲临床试验——TransEuro（试验注册号：NCT01898390）——应运而生。它集合了欧洲顶尖的专家，旨在吸取过往经验，优化移植方案，看看hfVM移植能否真正成为治疗PD的有效手段。移植效果如何？面临了哪些困难？那些移植进去的细胞真的像预期那样工作了吗？试验结果已然揭晓，它没有带来简单的成功故事，却为我们描绘了一幅复杂而真实的画面，揭示了细胞治疗的艰辛与突破方向，尤其为当下正如火如荼进行的干细胞（stem cell）替代疗法试验提供了至关重要的经验。（5月2日《Nature Biotechnology》 “The TransEuro open-label trial of human fetal ventral mesencephalic transplantation in patients with moderate Parkinson’s disease”）理想很丰满，现实骨感：组织去哪儿了？TransEuro试验计划招募更多的病人进行移植，但现实却给了他们不小的挑战。由于人类胎儿腹侧中脑组织的可获得性非常差（poor availability），尽管试验涉及两个手术中心（英国剑桥和瑞典隆德），并采用了相同的组织准备方案，但最终只有11位病人接受了移植手术。这远少于他们最初的计划人数。在这11位病人中，有10位接受了双侧移植，使用了来自3个胎儿的hfVM组织，每侧脑区使用等量组织。还有1位病人只接受了单侧移植，因为手术规划的不确定性和心理压力，他不想继续第二次手术了。组织来源的困难直接影响了试验的规模，这意味着分析结果可能受到小样本量和个体差异的影响。36个月后：期待的“神奇”效果出现了吗？试验的主要评估指标（primary outcome）是最后一次移植手术后36个月时，病人在“关”状态（OFF state，即停用多巴胺类药物12小时或更长时间后）的运动功能评分（UPDRS Part III score）。结果如何呢？坦率地说，对于整个移植组的11位病人而言，与手术前的基线水平相比，或者与没有接受手术的16位对照组病人相比，UPDRS Part III（OFF状态）评分没有显示出明显的整体改善。换句话说，从这个最核心的运动功能指标来看，移植手术没有带来预期的显著疗效。这个结果可能让一些人失望，毕竟细胞移植的初衷就是为了显著改善运动症状。但这并不意味着试验完全失败，我们还需要看更细致的数据，以及从中能学到什么。剥开数据看真相：哪些指标变好了？虽然整体运动评分没有显著变化，但试验也评估了一些次要指标（secondary outcomes）。在这些次要指标中，移植组的病人在左旋多巴等效日剂量（L-DOPA equivalent daily dose, LEDD）和病人报告的“关”状态时间百分比（% reported OFF time）上，显示出比对照组更好的结果。具体来说，在36个月时，移植组病人报告的平均LEDD变化是15.6毫克，而对照组的变化是306毫克，显示移植组的药物剂量需求更低。同时，移植组病人报告的平均“关”状态时间变化是-7.75%，而对照组是4.23%，表明移植组病人处于“关”状态的时间减少了。这些结果提示，即使主要运动评分没有整体改善，移植的细胞可能还是产生了一定的临床影响，降低了病人对药物的需求，并减少了疾病对日常生活的负面影响。这种影响是温和且缓慢出现的，不像安慰剂效应那样普遍且迅速。大脑的“地图”：PET影像捕捉到的变化为了更深入地了解移植细胞的存活和功能，研究人员对部分病人进行了PET影像扫描，用来评估大脑中的多巴胺系统和5-羟色胺系统。使用[18F]FDOPA示踪剂（反映多巴胺合成和储存），在移植后18个月时，8名接受了双侧移植并完成了PET扫描的病人中，平均多巴胺摄取（Kᵢ值）有所改善。这说明移植的细胞确实在尝试重建多巴胺功能。然而，这种改善程度并不高，只有1位病人的多巴胺摄取水平恢复到了接近正常水平（在正常范围的2个标准差以内）。这与之前一些成功案例中多巴胺水平显著恢复甚至正常化的情况有很大差距。与历史数据相比（之前的隆德系列病人），TransEuro组术后[18F]FDOPA Kᵢ相对于正常水平的增加和相对于术前水平的增加百分比都显著较低。使用[11C]PE2I示踪剂（反映多巴胺转运蛋白），在移植后，移植组病人的纹状体（striatum）多巴胺转运蛋白结合潜能（BPND）显著增加，进一步支持了移植细胞存活和功能重建的证据。同时，研究还使用了[11C]DASB示踪剂（反映5-羟色胺转运蛋白）。结果显示，移植组病人的纹状体（主要是壳核 putamen）5-羟色胺神经支配在移植后增加了。这与之前一项研究的结果一致，该研究提示移植组织中的5-羟色胺能神经元可能与移植后异动症的发生有关。PET影像数据与临床结果之间也发现了一些关联：壳核多巴胺参数（[18F]FDOPA Kᵢ和[11C]PE2I BPND）在移植后的变化与异动症评分（AIMS总分和整体严重程度评分）呈正相关。这再次提示了异动症与多巴胺功能恢复之间的复杂关系，以及可能涉及5-羟色胺系统。手术地点和工具的影响：细节决定成败？一个有趣但需要谨慎解读的发现是，两个手术中心（隆德和剑桥）的病人移植结果似乎存在差异。隆德中心的3位病人使用的是一种叫做R-L的移植工具（之前一些成功试验中也用过），而剑桥中心的8位病人使用的是两种新制造的TRN3和TRN4工具。虽然样本量太小，无法进行严格的统计分析，但从趋势上看，隆德的病人似乎比剑桥的病人获得了更多益处。研究人员认为，这可能与使用的手术工具不同有关。尽管组织准备流程标准化了，但移植工具的设计差异（如针头细节）可能会影响细胞递送的方式和效果。此外，病人选择（隆德的病人移植时疾病进展可能稍缓）和手术医生的操作经验也可能带来差异。这个发现强调了，在细胞移植这样的复杂疗法中，不仅细胞本身很重要，如何将细胞精准、温和地递送到目标位置也至关重要。安全性考量：风险与回报除了疗效，安全性是临床试验的另一个关键方面。总的来说，TransEuro试验的移植过程耐受性良好，没有发生与手术或免疫抑制相关的严重长期并发症导致残疾。在11位移植组病人中，有3位（27%）出现了异动症（GIDs），但都被描述为轻度（mild）且不需要额外的神经外科干预来治疗。这个发生率与之前一些试验报告的15-54%相比，处于较低或相似水平，但关键在于，这一次异动症的严重程度较低。正如PET影像所示，这可能与移植组织中的5-羟色胺神经元活动增加有关。此外，有2位移植组病人发生了颅内出血（intracerebral hemorrhages），但都没有导致长期的神经功能障碍。其中1位出血靠近移植区域，被认为与手术操作有关，症状在2周内消退。另1位出血在移植区域上方，没有症状。考虑到每次穿刺都有大约1%的出血风险，这个发生率（105次穿刺中有2次出血）在预期范围之内。有2位病人由于免疫抑制药物引起了并发症（如结肠炎、卡波西肉瘤），需要调整或停用药物。尽管出现了一些不良事件（adverse events），但大多数是轻微或与常规监测相关的异常检查结果（比如免疫抑制期间的血检异常），总的来说，没有出现导致病人永久性残疾或长期严重问题的并发症。面向未来：从“失败”中学习，迎接干细胞新时代TransEuro试验虽然没有达到其主要疗效目标，未能证明hfVM移植作为一种“常规”临床策略的可行性，但它提供了极其宝贵的经验和见解，特别是对于正在开启的新一代细胞疗法——基于干细胞的多巴胺神经元替代疗法。这项试验的失败，主要原因在于：组织来源不可靠： hfVM组织来源稀缺且不可预测，导致无法按计划进行移植，样本量小，难以进行充分的分析。组织质量和组分变异性：尽管努力标准化流程，但胎儿捐献者的孕周差异、组织处理过程的微小差异，以及难以进行充分的质量控制，都可能导致移植组织中细胞的质量和组分（比如5-羟色胺神经元的比例）存在变异性，进而影响疗效和安全性。细胞存活和功能不足：大多数病人移植后多巴胺能神经元的存活数量和对壳核的神经支配程度不足以恢复到接近正常水平，这可能是临床疗效不显著的根本原因。手术技术差异：不同手术工具的使用可能影响了细胞的递送效果，提示递送方法的重要性。TransEuro试验最重要的贡献在于，它为未来基于干细胞的PD细胞治疗试验奠定了基础，并指明了关键方向：标准化、高质量的细胞来源：需要使用批次生产、质量控制严格的干细胞来源（如诱导多能干细胞 iPSC 或胚胎干细胞 ES 细胞），确保移植细胞的一致性和可靠性，并且可以纯化，去除有害细胞亚群（如5-羟色胺能神经元）。优化细胞数量和递送：需要确定最佳的移植细胞数量和精确的递送技术，确保足够数量的细胞能够长期存活并在目标区域建立广泛的神经支配。精细的病人选择：尽早识别适合接受细胞治疗的病人，或根据疾病亚型进行分层。全面的评估方法：结合详细的临床评估和客观的影像学方法（如PET），长期监测细胞存活、功能和临床效果。设置合适的对照和研究设计：确保试验设计能够准确评估疗法的真实效果，避免安慰剂效应或自然病程的影响。目前，基于干细胞来源的多巴胺能神经前体细胞的PD治疗试验（如STEM-PD试验，注册号：NCT04802733）已经在全球范围内启动或即将启动。TransEuro试验的经验教训将极大地指导这些新试验的设计和执行，帮助研究者们避开过去的陷阱。TransEuro试验就像一座桥梁，连接了hfVM移植的过去和干细胞治疗的未来。虽然它自己没有完全成功地跨越到临床应用的彼岸，但它用数据和经验，照亮了通往下一代细胞治疗的道路。帕金森病的治疗之路漫长而曲折，细胞治疗仍然充满希望。从TransEuro试验中学到的这些宝贵知识，正是我们走向最终胜利的坚实基础。参考文献Barker RA, Lao-Kaim NP, Guzman NV, Athauda D, Bjartmarz H, Björklund A, Church A, Cutting E, Daft D, Dayal V, Dunnett S, Evans A, Grealish S, Hannaway N, He X, Hewitt S, Kefalopoulou Z, Mahlknecht P, Martín-Bastida A, Farrell K, Moore S, Bulstrode H, Nakornchai T, Nelander-Wahlestedt J, Roupé L, Paul G, Peall K, Rosser A, Roca-Fernández A, Rowlands S, McGorrian AM, Scherf C, Vinh NN, Roberton V, Kelly C, Lelos M, Torres E, Shires K, Hills R, Williams D, Roussakis AA, Sibley K, Tyers P, Wijeyekoon R, Williams-Gray C, Foltynie T, Piccini P, Morris R, Lazic SE, Lindvall O, Parmar M, Widner H; TransEuro consortium. The TransEuro open-label trial of human fetal ventral mesencephalic transplantation in patients with moderate Parkinson's disease. Nat Biotechnol. 2025 May 2. doi: 10.1038/s41587-025-02567-2. Epub ahead of print. PMID: 40316701.声明：本文仅用于分享，不代表平台立场，如涉及版权等问题，请尽快联系我们，我们第一时间更正，谢谢！往期热文：Cell | 颠覆认知！不是被动扩散，CD36介导内吞才是许多“大块头”药物入胞的秘密通道Nature Methods | mScarlet3-H：红色荧光蛋白的新一代王者！Nature Methods | 告别“平面时代”！光学显微镜如何带你看清3D细胞世界的秘密？Nature | 帕金森病新曙光！iPS细胞人体试验结果揭晓，安全有效性初显！Cell | 实时见证“基因之吻”：Oligo-LiveFISH高精度追踪增强子-启动子动态互作Nature Biotechnology | 重磅综述：不止CAR-T！唤醒免疫“特种部队”，工程化先天细胞开启抗癌新纪元

细胞疗法临床研究

2025-04-29

·生物谷

两篇Nature论文指出干细胞疗法有望安全有效治疗帕金森病

这两项临床试验均证实了干细胞衍生细胞产品异基因（非自身）移植治疗帕金森病的安全性。两项独立的临床试验证明了干细胞疗法治疗帕金森病的安全性。它们分别研究了人类诱导性多能干细胞（induced pluripotent stem cell）和人类胚胎干细胞（embryonic stem cell）衍生细胞的使用。然而，需要进一步的研究来测试这些疗法的有效性和临床益处。相关研究结果发表在Nature杂志上。帕金森病是一种神经退行性疾病，其特征是产生神经递质多巴胺的神经元逐渐丧失。尽管目前的治疗方法，如左旋多巴（L-dopa），可以在早期缓解症状，但它们的疗效会下降，并且经常伴有运动障碍（不自主运动）等副作用。细胞疗法，特别是补充大脑中产生多巴胺的神经元（多巴胺能神经元），可以提供一种潜在的更有效的治疗方法，减少不良反应。为了研究帕金森病细胞疗法的安全性和潜在副作用，Ryosuke Takahashi、Jun Takahashi及其同事们进行了一项I/II期临床试验。7名患者（年龄在50至69岁之间）的大脑两侧接受了来自人类诱导性多能干细胞的多巴胺能祖细胞移植。在24个月的研究期间，没有报告严重的不良事件，移植的多巴胺能祖细胞产生多巴胺，没有过度生长或形成肿瘤，从而避免了这两种与干细胞治疗相关的风险。研究人员还观察到，在不服用标准药物的情况下继续进行这项临床试验以进行疗效评估的六名参与者中，有四名参与者的帕金森病相关运动症状（该研究的次要结果）有所减轻，五名参与者在服用标准药物时也有所减轻。然而，这些结果因所使用的措施而异，一些措施显示变化很小。在另一项I期临床试验中，Viviane Tabar及其同事们探索了源自人类胚胎干细胞的多巴胺能神经元祖细胞产品（bemdaneprocel）的安全性。12名中位年龄为67岁的患者接受了将bemdaneprocel 移植到大脑两侧壳核的手术。5名参与者接受了低剂量（每个壳核90万个细胞）移植，7名参与者接受高剂量（每个壳核270万个细胞）移植。该细胞产品通常耐受良好，在18个月的随访期间没有报告与治疗相关的严重不良事件。没有发生以前与用于帕金森病治疗的胎儿组织移植相关的运动障碍。此外，在低剂量和高剂量队列中的患者中观察到运动功能的一些改善（该研究的次要结果）。然而，不同测量参数的改善程度各不相同。这两项临床试验均证实了干细胞衍生细胞产品异基因（非自身）移植治疗帕金森病的安全性。不过，它们也存在一些局限性，包括两项临床试验的样本量小和开放标签性质（这意味着研究人员和患者都知道谁在接受哪种类型的治疗）。然而，这两项独立试验都显示了安全性，并提示了可能的疗效，这是在更广泛的社会中建立利用细胞疗法治疗帕金森病的重要一步。（生物谷 Bioon.com）参考资料： Nobukatsu Sawamoto et al, Phase I/II trial of iPS-cell-derived dopaminergic cells for Parkinson's disease, Nature (2025). DOI: 10.1038/s41586-025-08700-0. V. Tabar et al, Phase I trial of hES cell-derived dopaminergic neurons for Parkinson's disease, Nature (2025). DOI: 10.1038/s41586-025-08845-y.

临床结果临床1期细胞疗法

2025-04-22

·PRNewswire

XADAGO/EQUFINA Set to Revolutionize Parkinson's Disease Treatment Landscape | DelveInsight

As a selective monoamine oxidase B (MAO-B) inhibitor, XADAGO offers a unique mechanism of action that complements traditional therapies, potentially improving motor function and reducing "off" time in patients. The increasing prevalence of Parkinson's disease and the growing demand for effective therapies create a substantial market opportunity for XADAGO, particularly in regions with aging populations. LAS VEGAS, April 22, 2025 /PRNewswire/ -- DelveInsight's " XADAGO/EQUFINA Market Size, Forecast, and Market Insight Report" highlights the details around XADAGO/EQUFINA, an inhibitor of monoamine oxidase B (MAO-B) indicated as an adjunctive treatment to levodopa/carbidopa in patients with Parkinson's disease experiencing "off" episodes. The report provides product descriptions, patent details, and competitor products (marketed and emerging therapies) of XADAGO/EQUFINA. The report also highlights the historical and forecasted sales from 2020 to 2034 segmented into 7MM [the United States, the EU4 (Germany, France, Italy, and Spain), the United Kingdom, and Japan]. Newron Pharmaceuticals/Eisai/Meiji Seika Pharma's XADAGO/EQUFINA (safinamide) Overview XADAGO is a monoamine oxidase B (MAO-B) inhibitor used alongside levodopa/carbidopa to help manage "off" episodes in individuals with Parkinson's disease. While its exact mode of action in treating Parkinson's is not fully understood, it is thought to work by inhibiting MAO-B, thereby reducing dopamine breakdown. This leads to increased dopamine levels and enhanced dopaminergic activity in the brain. XADAGO contains the active ingredient safinamide in the form of a mesylate salt and is available in 50 mg and 100 mg film-coated oral tablets. Each tablet provides either 65.88 mg or 131.76 mg of safinamide mesylate, equivalent to 50 mg or 100 mg of the safinamide base. The medication is marketed as XADAGO in the United States and Europe and under the name EQUFINA in Japan. Learn more about XADAGO/EQUFINA projected market size for Parkinson's disease @ XADAGO/EQUFINA Market Potential Parkinson's disease is a progressive neurological disorder that mainly impairs movement control. It results from the slow degeneration of dopamine-producing neurons in the brain, especially in the substantia nigra, a region crucial for managing voluntary motor function. According to estimates by DelveInsight, there were 2.7 million diagnosed prevalent cases of Parkinson's disease in the 7MM in 2023, with the United States accounting for around 45% of these cases. While a cure for Parkinson's remains elusive, a combination of pharmacological and non-pharmacological therapies is used to manage symptoms. Physical, occupational, and speech therapies form key components of treatment, and surgical procedures may benefit select patients. Additionally, complementary therapies are sometimes employed to help address particular symptoms. Frequently prescribed medications for Parkinson's include levodopa, dopamine agonists, MAO-B inhibitors, COMT inhibitors, amantadine, anticholinergics, and adenosine A2A antagonists. These treatments primarily target motor symptoms, which are a major concern for those affected. DelveInsight reports that the Parkinson's disease market in the 7MM was valued at USD 3.2 billion in 2023. The market is expected to grow over the forecast period (2020–2034), fueled by the launch of new therapies, increasing prevalence, better access to healthcare, and rising demand for more advanced and effective treatment options. Discover more about the Parkinson's disease market in detail @ Parkinson's Disease Market Report Emerging Competitors of XADAGO/EQUFINA Some of the drugs in the pipeline include Solengepras (Cerevance), Minzasolmin (UCB Biopharma SRL/Novartis), Buntanetap (Annovis Bio), and others. Buntanetap has successfully completed Phase III trials for early-stage Parkinson's disease. Annovis Bio has scheduled a meeting with the FDA in Q1 2025 to determine the development path forward for Buntanetap in the treatment of Parkinson's disease. Buntanetap is also being developed for Alzheimer's disease, Lewy Body Dementia, and other neurodegenerative disorders. In November 2024, Cerevance announced the dosing of the first patient in its pivotal Phase III ARISE trial, evaluating solengepras as a potential adjunctive treatment for Parkinson's disease. Cerevance expects to report topline data in the first half of 2026. In December 2021, UCB partnered with Novartis to globally co-develop and co-commercialize UCB0599, a pioneering alpha-synuclein misfolding inhibitor currently in Phase II clinical trials for Parkinson's disease. To know more about the number of competing drugs in development, visit @ XADAGO/EQUFINA Market Positioning Compared to Other Drugs Key Milestones of XADAGO/EQUFINA In April 2020, Newron Pharmaceutical acknowledged that US WorldMeds, who held the US commercialization rights for the licensed drug, XADAGO, as a sub licensee of Zambon, had entered into a definitive agreement with Supernus Pharmaceuticals under which Supernus would acquire the CNS portfolio of US WorldMeds, including the US rights to XADAGO In November 2019, Eisai announced that it had launched the EQUFINA 50mg tablets for the indication of improvement of the wearing-off phenomenon in patients with Parkinson's disease under treatment with a drug containing levodopa in Japan. Manufacturing and marketing approval of EQUFINA was obtained in September 2019. In April 2017, Eisai Co., Ltd. and Meiji Seika Pharma announced entering into a license agreement for the commercialization of safinamide (development code: ME2125) to treat Parkinson's disease in Japan and Asia. In March 2017, Newron Pharmaceuticals announced the US FDA approval of XADAGO to treat Parkinson's disease as an add-on therapy to levodopa/carbidopa for patients experiencing "off" episodes. In March 2016, Zambon announced a strategic agreement with US WorldMeds to commercialize Newron's lead compound, XADAGO, to treat Parkinson's disease in the US. In February 2015, XADAGO was approved in the European Union as an add-on therapy to levodopa, alone or in combination with other Parkinson's medications, in mid-late stage PD patients with motor fluctuations. XADAGO/EQUFINA Patent Details XADAGO tablets are currently protected by three XADAGO patents with US patent numbers 8,076,515, 8,278,485, and 8,283,380, which expire between June 2027 and December 2028 and are listed in the FDA's publication, Approved Drug Products with Therapeutic Equivalence Evaluations, commonly referred to as the Orange Book. The company has a license agreement with Zambon S.p.A., Newron's partner, related to the XADAGO Patents, and as a new chemical entity, XADAGO is under the 5-year FDA exclusivity period that expires on March 21, 2022. In May 2017, Zambon filed a worldwide patent under the patent number WO2017207587A1. The invention relates to pharmaceutical compositions comprising safinamide and, more particularly, to taste-masked particles comprising said active ingredient or pharmaceutically acceptable salts thereof, oral dosage forms that include said particles, and a process for preparing them. Discover how XADAGO/EQUFINA is shaping the Parkinson's disease treatment landscape @ XADAGO 50mg XADAGO/EQUFINA Market Dynamics XADAGO, marketed as EQUFINA in some regions (notably in South Korea and Japan), is a once-daily oral selective MAO-B inhibitor used as an add-on treatment for Parkinson's disease patients experiencing "off" episodes while on a stable dose of levodopa. The drug's unique dual mechanism of action—MAO-B inhibition and modulation of glutamate release—offers both dopaminergic and non-dopaminergic effects, positioning it as a differentiated product in the PD adjunctive therapy landscape. This has helped it carve a niche in markets where patients are inadequately controlled by levodopa alone, particularly those in mid-to-late-stage PD. The global market dynamics for XADAGO/EQUFINA are shaped by a mix of competitive intensity, regional adoption trends, and payer dynamics. In the U.S. and Europe, the drug has faced stiff competition from generic MAO-B inhibitors (like selegiline and rasagiline) and newer Parkinson's disease therapies, including COMT inhibitors, dopamine agonists, and extended-release levodopa formulations. Despite this, its favorable safety profile and once-daily dosing have supported its uptake in certain patient segments, especially in Europe. Market penetration has been slower in the U.S. due to both reimbursement hurdles and physician preference for more established adjunctive treatments. In Asia, particularly Japan and South Korea, EQUFINA has demonstrated stronger market performance thanks to focused commercial strategies and a high unmet need for effective "off time" management. Meiji Seika Pharma and Eisai, the regional marketing partners, have successfully leveraged the drug's differentiated profile in clinician education, which has led to growing adoption among neurologists. In Japan, where the aging population is rapidly expanding and Parkinson's prevalence is rising, EQUFINA has benefited from both demographic tailwinds and formulary access. Looking ahead, the market outlook for XADAGO/EQUFINA depends on several strategic levers, including lifecycle management, regional partnerships, and real-world evidence generation. The manufacturer's ability to expand into new geographies, secure favorable reimbursement, and differentiate against both generics and newer entrants will be critical. Moreover, as Parkinson's disease treatment moves toward more personalized approaches, XADAGO/EQUFINA may find sustained relevance in specific subpopulations, particularly those requiring a balance of efficacy and tolerability. Dive deeper to get more insight into XADAGO/EQUFINA's strengths & weaknesses relative to competitors @ XADAGO/EQUFINA Market Drug Report Table of Contents Related Reports Parkinson's Disease Market Parkinson's Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Parkinson's disease companies, including UCB Biopharma SRL, Novartis, Annovis Bio, Supernus Pharmaceuticals, Inc., Britannia Pharmaceutical, Pharma Two B, Mitsubishi Tanabe Pharma (NeuroDerm), AbbVie, Cerevel Therapeutics, Cerevance, among others. Parkinson's Disease Pipeline Parkinson's Disease Pipeline Insight – 2025 report provides comprehensive insights about the pipeline landscape, pipeline drug profiles, including clinical and non-clinical stage products, and the key Parkinson's disease companies, including Cerevel Therapeutics, Inhibikase Therapeutics, Neuraly, Peptron, Biogen, Roche, Brain Neurotherapy Bio, Inc., Modag, Annovis Bio Inc., BioVie Inc., United Neuroscience Ltd., Luye Pharma Group, AbbVie, UCB Biopharma SRL, InnoMedica Schweiz AG, Integrative Research Laboratories AB, H. Lundbeck A/S, Shanghai WD Pharmaceutical Co., Ltd., Cerevance Beta, Inc., Nobilis Therapeutics Inc., BlueRock Therapeutics, Taiwan Mitochondrion Applied Technology Co., Ltd., among others. Cell and Gene Therapy in Parkinson's Disease Market Cell and Gene Therapy in Parkinson's Disease Market Insights, Epidemiology, and Market Forecast – 2034 report deliver an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key cell and gene therapy in Parkinson's disease companies including MeiraGTx, Hope Biosciences, Sumitomo Pharma, Prevail Therapeutics, BlueRock Therapeutics, Voyager Therapeutics, among others. Parkinson's Disease Psychosis Market Parkinson's Disease Psychosis Market Insights, Epidemiology, and Market Forecast – 2034 report delivers an in-depth understanding of the disease, historical and forecasted epidemiology, as well as the market trends, market drivers, market barriers, and key Parkinson's disease psychosis companies, including Sumitomo Pharma America Inc., Vanda Pharmaceuticals, Acadia Pharmaceuticals Inc., Otsuka America Pharmaceutical, Lundbeck LLC, Jazz Pharmaceuticals, Alkahest Inc., Sandoz, Sio Gene Therapies, Axovant Sciences Ltd, among others. About DelveInsight DelveInsight is a leading Business Consultant and Market Research firm focused exclusively on life sciences. It supports pharma companies by providing comprehensive end-to-end solutions to improve their performance. Get hassle-free access to all the healthcare and pharma market research reports through our subscription-based platform PharmDelve . Contact Us Shruti Thakur [email protected] +14699457679 Logo: SOURCE DelveInsight Business Research, LLP WANT YOUR COMPANY'S NEWS FEATURED ON PRNEWSWIRE.COM? 440k+ Newsrooms & Influencers 9k+ Digital Media Outlets 270k+ Journalists Opted In GET STARTED

临床3期上市批准引进/卖出临床2期

100 项与左旋多巴相关的药物交易

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KEGG	Wiki	ATC	Drug Bank
D00059	左旋多巴	N04BA01	DB01235

研发状态

批准上市

10 条最早获批的记录,

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适应症	国家/地区	公司	日期
帕金森病	日本	Alfresa Pharma Corp.	1971-10-07

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适应症	最高研发状态	国家/地区	公司	日期
哮喘	临床1期	美国	Acorda Therapeutics, Inc.	2015-12-01
吸烟	临床1期	美国	Acorda Therapeutics, Inc.	2015-12-01
运动失调	临床1期	美国	AbbVie, Inc.	2009-06-01
运动失调	临床1期	新西兰	AbbVie, Inc.	2009-06-01
运动失调	临床1期	德国	AbbVie, Inc.	2009-06-01
帕金森病	临床1期	美国	Shire Development LLC	1970-06-04
帕金森病	临床1期	美国	Hoffmann-La Roche, Inc.	1970-06-04

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临床结果

适应症

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研究	分期	人群特征	评价人数	分组	结果	评价	发布日期


EAN2024	N/A	帕金森病	-	Inhaled levodopa	膚齋襯鹹獵網遞顧淵襯(獵鑰構餘膚觸蓋鏇選夢) = reported by 12 (66.7%) patients 衊壓鹹獵顧艱繭鏇願遞 (製夢齋築憲製壓憲餘獵 ) 更多	-	2024-06-28
INVEST study (MDS2023)	N/A	帕金森病	-	Continuous intrajejunal levodopa infusion (CILI)	繭餘齋齋襯範繭鑰鹹顧(膚蓋觸製觸鑰襯憲夢淵) = 鑰觸淵遞願顧積製齋鬱襯鑰選積構糧鬱糧積艱 (構簾淵糧簾網選網構簾, -2.9 ~ 11.0)	-	2023-08-27
Parkinson’s Progression Markers Initiative (PPMI) (MDS2023)	N/A	帕金森病	428	levodopa	鑰鏇積繭壓窪艱鏇鏇構(簾壓積積壓築築壓餘壓) = 膚鑰糧蓋繭廠蓋淵築積顧壓衊鹽製淵鹹餘淵鏇 (蓋遞範網簾膚範願襯糧 )	-	2023-08-27
				levodopa	鑰鏇積繭壓窪艱鏇鏇構(簾壓積積壓築築壓餘壓) = 艱範網夢築積選窪網憲顧壓衊鹽製淵鹹餘淵鏇 (蓋遞範網簾膚範願襯糧 )
PD MED early disease randomisation (MDS2023)	N/A	帕金森病	1,593	Levodopa-sparing therapy (dopamine agonist or monoamine oxidase B inhibitor)	蓋蓋憲鏇鏇鹽壓齋網積(鬱簾糧顧積構顧壓衊衊): P-Value = 0.84 更多	积极	2023-08-27
				Levodopa alone
MDS2023	N/A	肌张力障碍	-	Pre-levodopa administration	鏇夢醖築繭鏇窪淵構醖(糧廠願憲糧醖網膚願築) = 鏇繭蓋鬱築餘遞繭齋淵襯簾鹹繭膚壓蓋簾範膚 (衊構齋構遞簾觸積網願 )	-	2023-08-27
				Post-levodopa administration	鏇夢醖築繭鏇窪淵構醖(糧廠願憲糧醖網膚願築) = 鹽簾觸蓋築範獵窪艱繭襯簾鹹繭膚壓蓋簾範膚 (衊構齋構遞簾觸積網願 )
MDS2023	N/A	帕金森病	-	levodopa	衊築顧蓋淵窪餘遞鬱淵(構憲襯憲衊簾遞築餘築) = 襯夢簾淵艱齋窪壓製壓醖憲襯憲網簾選繭鏇糧 (積觸壓鹽鹹淵顧簾範膚 )	积极	2023-08-27
				levodopa	遞鑰獵糧廠蓋獵鹽餘鏇(夢鹹憲襯範選憲淵淵襯) = 繭壓製築顧鏇鏇獵獵積鹽鏇製鑰艱膚構夢獵壓 (選膚範積壓艱築遞鬱齋 ) 更多
EAN2023	N/A	-	-	levodopa (PD patients with RBD)	醖構鹹遞艱選衊艱鬱餘(繭淵齋簾糧遞範鏇窪範) = 鑰鑰願構築鹽艱鬱鬱簾遞窪願鏇鹹淵憲鑰顧廠 (壓製鑰夢選醖壓選餘製 )	-	2023-06-28
				levodopa (PD patients without RBD)	醖構鹹遞艱選衊艱鬱餘(繭淵齋簾糧遞範鏇窪範) = 壓鬱襯憲窪觸鹹淵廠醖遞窪願鏇鹹淵憲鑰顧廠 (壓製鑰夢選醖壓選餘製 )
WPC2023	N/A	帕金森病	-	levodopa (PwPD with ISA of LID (ISA+))	積築獵糧憲簾蓋鏇遞壓(鬱網襯鹹鹹窪鹽夢糧範) = 簾繭衊範襯網製積艱範蓋淵網製觸構壓淵鹹窪 (廠餘鏇積淵繭製鑰窪糧 )	-	2023-06-28
WPC2023	N/A	帕金森病	-	levodopaLCIGdopa (LCIG home-titration with telemedicine-assisted technology)	膚遞鹹願艱築衊膚憲餘(築構餘壓餘鹽窪繭襯製) = 觸壓蓋餘膚夢鏇簾選糧憲襯鏇選夢鹽簾蓋糧鏇 (壓製願獵淵鑰簾艱顧衊 ) 更多	-	2023-06-28