更新于：2024-09-19

PINK1

更新于：2024-09-19

基本信息

别名

BRPK、PARK6、Parkinson disease (autosomal recessive) 6

+ [5]

简介

Serine/threonine-protein kinase which protects against mitochondrial dysfunction during cellular stress by phosphorylating mitochondrial proteins such as PRKN and DNM1L, to coordinate mitochondrial quality control mechanisms that remove and replace dysfunctional mitochondrial components (PubMed:14607334, PubMed:18957282, PubMed:18443288, PubMed:15087508, PubMed:19229105, PubMed:19966284, PubMed:20404107, PubMed:22396657, PubMed:20798600, PubMed:23620051, PubMed:23754282, PubMed:23933751, PubMed:24660806, PubMed:24898855, PubMed:24751536, PubMed:24784582, PubMed:24896179, PubMed:25527291, PubMed:32484300, PubMed:20547144). Depending on the severity of mitochondrial damage and/or dysfunction, activity ranges from preventing apoptosis and stimulating mitochondrial biogenesis to regulating mitochondrial dynamics and eliminating severely damaged mitochondria via mitophagy (PubMed:18443288, PubMed:23620051, PubMed:24898855, PubMed:20798600, PubMed:20404107, PubMed:19966284, PubMed:32484300, PubMed:22396657, PubMed:32047033, PubMed:15087508). Mediates the translocation and activation of PRKN at the outer membrane (OMM) of dysfunctional/depolarized mitochondria (PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291). At the OMM of damaged mitochondria, phosphorylates pre-existing polyubiquitin chains at 'Ser-65', the PINK1-phosphorylated polyubiquitin then recruits PRKN from the cytosol to the OMM where PRKN is fully activated by phosphorylation at 'Ser-65' by PINK1 (PubMed:19966284, PubMed:20404107, PubMed:20798600, PubMed:23754282, PubMed:24660806, PubMed:24751536, PubMed:24784582, PubMed:25474007, PubMed:25527291). In damaged mitochondria, mediates the decision between mitophagy or preventing apoptosis by promoting PRKN-dependent poly- or monoubiquitination of VDAC1; polyubiquitination of VDAC1 by PRKN promotes mitophagy, while monoubiquitination of VDAC1 by PRKN decreases mitochondrial calcium influx which ultimately inhibits apoptosis (PubMed:32047033). When cellular stress results in irreversible mitochondrial damage, functions with PRKN to promote clearance of damaged mitochondria via selective autophagy (mitophagy) (PubMed:14607334, PubMed:20798600, PubMed:20404107, PubMed:19966284, PubMed:23933751, PubMed:15087508). The PINK1-PRKN pathway also promotes fission of damaged mitochondria by phosphorylating and thus promoting the PRKN-dependent degradation of mitochondrial proteins involved in fission such as MFN2 (PubMed:18443288, PubMed:23620051, PubMed:24898855). This prevents the refusion of unhealthy mitochondria with the mitochondrial network or initiates mitochondrial fragmentation facilitating their later engulfment by autophagosomes (PubMed:18443288, PubMed:23620051). Also promotes mitochondrial fission independently of PRKN and ATG7-mediated mitophagy, via the phosphorylation and activation of DNM1L (PubMed:18443288, PubMed:32484300). Regulates motility of damaged mitochondria by promoting the ubiquitination and subsequent degradation of MIRO1 and MIRO2; in motor neurons, this likely inhibits mitochondrial intracellular anterograde transport along the axons which probably increases the chance of the mitochondria undergoing mitophagy in the soma (PubMed:22396657). Required for ubiquinone reduction by mitochondrial complex I by mediating phosphorylation of complex I subunit NDUFA10 (By similarity). Phosphorylates LETM1, positively regulating its mitochondrial calcium transport activity (PubMed:29123128).

关联

项与 PINK1 相关的药物

ABBV-1088

靶点

PINK1

作用机制

PINK1 inhibitors

在研机构

AbbVie, Inc.

原研机构

AbbVie, Inc.

在研适应症

帕金森病

非在研适应症-

最高研发阶段临床1期

首次获批国家/地区-

首次获批日期1800-01-20

MTK-458

靶点

PINK1

作用机制

PINK1激活剂 [+1]

在研机构

Mitokinin, Inc.初创企业

原研机构

Mitokinin, Inc.初创企业

在研适应症

神经系统变性病

非在研适应症

帕金森病

最高研发阶段临床前

首次获批国家/地区-

首次获批日期1800-01-20

项与 PINK1 相关的临床试验

NCT06579300 / Not yet recruiting临床1期

A Phase 1 Multiple Ascending Dose, Drug-Drug Interaction, and Asian Pharmacokinetic Study of ABBV-1088

This study will assess the safety, tolerability, and pharmacokinetics of ABBV-1088 in healthy adult Western, Han-Chinese and Japanese participants. This study will also assess drug-drug interaction between itraconazole and ABBV-1088 in healthy adult Western participants.

开始日期2024-09-04

申办/合作机构

AbbVie, Inc.

NCT06414798 / Recruiting临床1期

A First-in-Human Single Ascending Dose and Mass Balance Study to Evaluate the Safety, Tolerability, and Pharmacokinetics of ABBV-1088 in Healthy Adult Subjects

This study will assess the single dose safety, tolerability and pharmacokinetic properties of ABBV-1088 in healthy adult participants

开始日期2024-05-13

申办/合作机构

AbbVie, Inc.

100 项与 PINK1 相关的临床结果

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100 项与 PINK1 相关的转化医学

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0 项与 PINK1 相关的专利（医药）

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4,040

项与 PINK1 相关的文献（医药）

2025-04-01·Neural Regeneration Research

Differential distribution of PINK1 and Parkin in the primate brain implies distinct roles

Article

作者: Wang, Qi ; Wen, Jiayi ; Liu, Yanting ; Huang, Wei ; Xu, Ting ; Chen, Xiusheng ; Xiong, Xin ; Li, Xiaojiang ; Zhao, Xianxian ; Yang, Weili ; Li, Shihua

JOURNAL/nrgr/04.03/01300535-202504000-00028/figure1/v/2024-07-06T104127Z/r/image-tiff The vast majority of in vitro studies have demonstrated that PINK1 phosphorylates Parkin to work together in mitophagy to protect against neuronal degeneration. However, it remains largely unclear how PINK1 and Parkin are expressed in mammalian brains. This has been difficult to address because of the intrinsically low levels of PINK1 and undetectable levels of phosphorylated Parkin in small animals. Understanding this issue is critical for elucidating the in vivo roles of PINK1 and Parkin. Recently, we showed that the PINK1 kinase is selectively expressed as a truncated form (PINK1–55) in the primate brain. In the present study, we used multiple antibodies, including our recently developed monoclonal anti-PINK1, to validate the selective expression of PINK1 in the primate brain. We found that PINK1 was stably expressed in the monkey brain at postnatal and adulthood stages, which is consistent with the findings that depleting PINK1 can cause neuronal loss in developing and adult monkey brains. PINK1 was enriched in the membrane-bound fractionations, whereas Parkin was soluble with a distinguishable distribution. Immunofluorescent double staining experiments showed that PINK1 and Parkin did not colocalize under physiological conditions in cultured monkey astrocytes, though they did colocalize on mitochondria when the cells were exposed to mitochondrial stress. These findings suggest that PINK1 and Parkin may have distinct roles beyond their well-known function in mitophagy during mitochondrial damage.

2025-01-01·Journal of Ethnopharmacology

Naoxintong capsule accelerates mitophagy in cerebral ischemia-reperfusion injury via TP53/PINK1/PRKN pathway based on network pharmacology analysis and experimental validation

Article

ETHNOPHARMACOLOGICAL RELEVANCEThe incidence and mortality of cerebrovascular diseases are increasing year by year. Cerebral ischemia-reperfusion injury (CIRI) is common in patients with ischemic stroke. Naoxintong (NXT) is composed of a variety of Chinese medicines and has the ability to treat CIRI.AIM OF THE STUDYThe aim of this study is to investigate whether NXT regulates mitophagy in CIRI based on network pharmacology analysis and experimental validation.MATERIALS AND METHODSOxygen and glucose deprivation/re-oxygenation (OGD/R, 2/22 h) model of PC12 cells and transient middle cerebral artery occlusion (tMCAO, 2/22 h) model of rats were established. Pharmacodynamic indicators include neurological deficit score, 2,3,5-triphenyte-trazoliumchloride (TTC) staining, hematoxylin-eosin (HE) staining and cell viability. Network pharmacology was used to predict pharmacological mechanisms. Pharmacological mechanism indexes include transmission electron microscopy (TEM), drug affinity responsive target stability (DARTS), cellular thermal shift assay (CETSA), immunohistochemistry (IHC), western blot (WB) and immunofluorescence (IF). Kevetrin (an agonists of p53) and pifithrin-α (an inhibitor of p53) used to detect the key role of p53 in mitophagy of NXT.RESULTSNXT (1% serum containing NXT and 110 mg/kg) improved the damage of OGD/R PC12 cells and tMCAO rats, and this protective effect was related to the anti-oxidation and ability to promote mitophagy of NXT. NXT and pifithrin-α increased the expression of promoting-mitophagy targets (PINK1, PRKN and LC3B) and inhibited the expression of inhibiting-mitophagy targets (p52) via restraining p53, and finally accelerated mitophagy caused by CIRI.CONCLUSIONThis study demonstrates that NXT promotes mitophagy in CIRI through restraining p53 and promoting PINK1/PRKN in vivo and in vitro.

2025-01-01·Domestic Animal Endocrinology

Impact of quercetin on autophagy and apoptosis induced by a high concentration of CuSO4 in porcine ovarian granulosa cells

Article

作者: Liu, Jiying ; Li, Mengxuan ; Qi, Nannan ; Xing, Wenwen ; Wang, Binbin

Copper is a vital micronutrient necessary for the maintenance of physiological functions. However, excessive amounts can lead to organ damage. Porcine ovarian granulosa cells are damaged by a high concentration of CuSO₄, which can reduce the reproductive capacity of sows. Quercetin has shown remarkable efficacy in mitigating the harmful effects of heavy metals. Therefore, the aim of this study was to investigate the effects of a high concentration of CuSO₄ on autophagy and apoptosis in porcine ovarian granulosa cells and to explore whether quercetin can counteract these toxic effect. Cell morphology, and the mRNA expression levels of autophagy-related genes (LC3-Ⅰ, ATG5, ATG7, ATG12, Beclin1, mTOR, LC3-Ⅱ and P62) were significantly changed upon treatment with 200 and 400 µM CuSO₄. Treatment with 200 µM CuSO₄ increased expression of P62 protein (P<0.05), promoted LC3-Ⅰ to LC3-Ⅱ conversion (P<0.05), and reduced PINK1 protein expression and the ATP content (P<0.05). In addition, expression of Caspase3 protein was increased and TUNEL staining indicated that the number of apoptotic cells was increased. However, co-treatment with 10 µM quercetin significantly decreased expression of P62 and conversion of LC3-Ⅰ to LC3-Ⅱ. Furthermore, flow cytometric analysis revealed that addition of 10 µM quercetin significantly reduced apoptosis induced by a high concentration of CuSO₄. In summary, the results indicate that a high concentration of CuSO₄ can trigger mitochondrial and autophagy dysfunction, activate mitochondrial apoptosis pathway, and exert cytotoxic effects. Quercetin can mitigate autophagy dysfunction, enhance autophagic processes, and alleviate apoptosis.

项与 PINK1 相关的新闻（医药）

2024-08-01

·GlobeNewswire-Health Care

CENTOGENE Publication in Brain Journal Reveals 15% of Parkinson’s Disease Cases Are Linked to Genetic Factors

Initial data from largest international Parkinson’s disease patient cohort shows approximately 90% of these genetically confirmed patients had variants in the LRRK2 or GBA1 genes, making these individuals potential candidates to be included in gene-targeted trialsThe Rostock International Parkinson's Disease (ROPAD) Study aims to characterize the genetics of Parkinson’s disease (PD) to establish a better understanding of disease progression, diagnosis, and treatment for patients CAMBRIDGE, Mass. and ROSTOCK, Germany and BERLIN, Aug. 01, 2024 (GLOBE NEWSWIRE) -- Centogene N.V. (Nasdaq: CNTG), the essential life science partner for data-driven answers in rare and neurodegenerative diseases, today announced data from the Company’s Rostock International Parkinson's Disease (ROPAD) Study revealing the genetic factors and prevalence of Parkinson’s disease (PD). The findings from this landmark study indicate that approximately 15% of PD-related cases are tied to genetic variants, with the majority being linked to LRRK2 and GBA1. The data was published in Brain in a paper titled, “Relevance of genetic testing in the gene-targeted trial era: the Rostock Parkinson’s disease study.” “Over the past five years, CENTOGENE and our more than 100 study sites around the world have worked together to diagnose Parkinson’s patients and accelerate treatment options,” said Prof. Peter Bauer, Chief Medical and Genomic Officer at CENTOGENE. “Our collaborative work clearly shows how significant of a role genetics plays in Parkinson’s disease and underscores the need to integrate genetic testing in routine care of these patients. This will not only enable access to potentially available treatments, but will de-risk and accelerate the development of gene-specific therapies – driving the future of Parkinson’s disease patient care.” The research investigated variants in 50 genes with either an established relevance for PD or possible phenotypic overlap from over 12,500 patients from 16 countries who have been enrolled in CENTOGENE’s ROPAD Study. In more than 1,800 participants, a PD-relevant genetic test (PDGT) provided a positive result. This included variants linked to the LRRK2 and GBA1 genes, as well as PRKN, SNCA, and PINK1, or a combination of genetic findings in multiple genes. In the emerging era of gene-targeted PD clinical trials, the Company’s findings that approximately 15% of patients harbor potentially actionable genetic variants offers an important prospect to affected individuals and their families and underlines the need for genetic testing in PD patients. By capturing such genetic data, this also allows for differential genetic counselling across the spectrum of different ages at onset and family histories. The Company recently launched a ROPAD Consortium to continue driving PD research and treatment through collaborative efforts. The ROPAD Consortium will build on the vast network of neurologists, existing partnerships with non-profit organizations, and the largest genetic testing program for PD patients worldwide to streamline access to critical data, drive impactful research, and improve the potential for advancing treatment options. To find out more, email: contact.pharma@centogene.com About ROPAD The Rostock International Parkinson's Disease (ROPAD) Study is a global epidemiological study focusing on the role of genetics in Parkinson’s disease (PD). The major goal of the study is to characterize the genetics of PD to establish a better understanding of the disease etiology, diagnosis, and severity. CENTOGENE utilizes CentoCard®, the Company’s proprietary, CE-marked Dried Blood Spot (DBS) collection kit in combination with state-of-the-art sequencing technologies to screen for mutations in LRRK2 and other PD-associated genes. To date, over 18,000 participants from around the world have been tested over a five-year period. About CENTOGENE CENTOGENE’s mission is to provide data-driven, life-changing answers to patients, physicians, and pharma companies for rare and neurodegenerative diseases. We integrate multiomic technologies with the CENTOGENE Biodatabank – providing dimensional analysis to guide the next generation of precision medicine. Our unique approach enables rapid and reliable diagnosis for patients, supports a more precise physician understanding of disease states, and accelerates and de-risks targeted pharma drug discovery, development, and commercialization. Since our founding in 2006, CENTOGENE has been offering rapid and reliable diagnosis – building a network of approximately 30,000 active physicians. Our ISO, CAP, and CLIA certified multiomic reference laboratories in Germany utilize Phenomic, Genomic, Transcriptomic, Epigenomic, Proteomic, and Metabolomic datasets. This data is captured in our CENTOGENE Biodatabank, with over 850,000 patients represented from over 120 highly diverse countries, over 70% of whom are of non-European descent. To date, the CENTOGENE Biodatabank has contributed to generating novel insights for more than 300 peer-reviewed publications. By translating our data and expertise into tangible insights, we have supported over 50 collaborations with pharma partners. Together, we accelerate and de-risk drug discovery, development, and commercialization in target and drug screening, clinical development, market access and expansion, as well as offering CENTOGENE Biodata Licenses and Insight Reports to enable a world healed of all rare and neurodegenerative diseases. To discover more about our products, pipeline, and patient-driven purpose, visit www.centogene.com and follow us on LinkedIn. Contacts:Melissa HallCENTOGENECorporate Communications Press@centogene.com Lennart StreibelCENTOGENEInvestor Relations IR@centogene.com

临床研究

2024-06-27

·生物制药小编

艾伯维帕金森疗法再遭FDA CRL抨击

近日（6月25日），艾伯维宣布已经收到FDA关于该公司帕金森新药ABBV-951上市申请（NDA）的完整回复函（CRL）。事实上这已经不是ABBV-951第一次收到CRL了，在去年3月时，艾伯维收到了FDA针对ABBV-951的NDA的第一份CRL，当时的问题主要涉及ABBV-951用来给药的泵，而现在的问题则出在了第三方制造商。之前出问题的泵帕金森病是一种常见的中老年神经系统退行性疾病，病理改变主要以黑质多巴胺神经元丢失以及α-突触核蛋白聚集体为主，而常见药物左旋多巴虽然能够通过补充脑内的多巴胺水平来帮助患者缓解运动障碍等症状，但无法做到根治，可能随着药效波动伴有明显副作用（例如：开关现象），且并不能逆转疾病的进展。而ABBV-951的思路则是通过皮下注射的泵来维持24小时持续注射，虽然ABBV-951药物本身只是左旋多巴/卡比多巴的前体，但相比传统治疗，胜在药物副作用的减少。在一项关键的3期临床试验M15-736 Study中，使用泵进行持续皮下输注给药的ABBV-951组与口服左旋多巴/卡比多巴组相比，在“开启”（即症状缓解）时间和“关闭”（即出现运动障碍症状）时间方面均表现出显著的优势。这进一步证明了使用泵进行递送的有效性。之前因为泵出问题，让艾伯维推迟了9个月才在去年12月重新递交NDA。但现在艾伯维方面的问题似乎已经解决，问题又出现在了第三方制造商上，严重拖延了ABBV-951上市的进度，可以说较为可惜。艾伯维押注帕金森市场虽然此次面临失利，艾伯维似乎对于帕金森市场相当感兴趣，近年来动作频频。在去年10月以总额6.5亿美元（1.1亿美元预付+4.5亿美元里程碑）收购了Mitokinin公司并获得了PINK1激活剂以治疗帕金森，具体机制是利用PINK1维持线粒体功能的作用来改善帕金森。（有研究表明PINK1的功能丧失与家族性帕金森有关）有趣的是，在递交NDA的去年12月，艾伯维还以87亿美元收购了CNS疾病开发公司Cerevel，这家公司前身是辉瑞的CNS部门，后来被拆分出来通过贝恩资本的注资成为一家公司。该公司目前的核心管线是tavapadon，也是一款帕金森药物，是一款D1/D5部分激动剂。 D1和D5受体属于多巴胺受体家族，分别调控运动控制和认知功能，正常情况下常常会与多巴胺结合，但在帕金森患者中，多巴胺神经元丢失，缺乏多巴胺作用，因此tavapadon与D1/D5受体结合，就可以模拟多巴胺的作用，进而改善帕金森病患者的症状。今年4月发布的关键III期临床数据显示，tavapadon达到了主要终点，与安慰剂相比，在27周内，运动障碍的总“正常”时间有统计学意义上的显著增加。参考来源： https://news.abbvie.com/2024-06-25-AbbVie-Provides-U-S-Regulatory-Update-on-ABBV-951-Foscarbidopa-Foslevodopa

临床3期并购申请上市

2024-04-12

·GBIHealth

帕金森：新疗法已在路上

帕金森病（Parkinson's disease，简称PD）帕金森病是仅次于阿尔茨海默病（AD）的第二大神经退行性疾病，于1817年由James Parkinson医生最早描述其症状，并以他的名字命名。作为常见的中老年神经系统退行性疾病，临床表现为震颤、肌强直、姿势平衡障碍等运动症状和睡眠障碍、自主神经功能障碍、认知和精神障碍等非运动症状，中晚期阶段常伴有运动并发症，严重影响患者的生活质量。变，万物随阳气上升而萌芽生长。 “ 据统计，全球范围内约有1000多万名患者饱受帕金森病的困扰。而我国的帕金森病患者人数预计将从2005年的199万人上升到2030年的近500万人，几乎占到全球帕金森病患病人数的一半。”发病机制帕金森的主要病理变化发生在中脑黑质腹侧的致密部，该区含有大量多巴胺神经元，患者致密部神经元大量死亡，有的甚至丧失高达70%的神经元，导致多巴胺的缺乏以及动作、边缘系统等神经回路的故障。二十世纪60年代研究发现，多巴胺前体化合物左旋多巴对帕金森症有治疗效果，直到今天仍是治疗帕金森的主力药物。然而，多巴胺制剂只能缓解帕金森症状，治标不治本，且副作用较大。后续研究发现，大脑黑质的病变与α-突触核蛋白有关，这种蛋白异常积聚，形成纤维蛋白沉淀并最终导致神经细胞死亡。α-突触核蛋白是可溶性蛋白，导致其异常聚集通常伴随着免疫激活、神经炎症、线粒体功能障碍以及溶酶体和内体功能的改变。研究者发现，这些病理过程与基因密切相关。比如，具有PRKN基因突变和主要线粒体功能障碍的患者表现出一种受限的细胞丧失模式，主要局限在黑质纹状体系统中，没有典型散发性帕金森病中所见的广泛病理和非运动特征。相反，具有SNCA或GBA突变，且α-突触核蛋白病理明显的患者在早期表现出非运动特征，包括自主神经功能障碍和痴呆，可能反映了全身和大脑中的广泛病理。这些风险基因不一定与α-突触核蛋白的病理直接相关。目前已经确定七个基因作为单基因病因，其中四个导致晚发性、常染色体显性遗传疾病（即LRRK2、CHCHD2、VPS35和SNCA），三个导致早发性、常染色体隐性遗传疾病（即PARKIN、DJ1和PINK1）。第八个基因GBA的变异是帕金森病的最常见遗传风险因素。未来有望开发出针对专门靶点的治疗药物。主要治疗思路流程除多巴胺制剂之外，儿茶酚-氧位-甲基转移酶抑制剂以及单胺氧化酶B型抑制剂也是帕金森的常用药物。根据《2020年中国帕金森病治疗指南》，对早发型、晚发型帕金森病，根据主要症状的不同选择不同的治疗方案（图1）。图1.患者用药选择流程图参考来源：《2020年中国帕金森病治疗指南》；DAs：多巴胺受体激动剂；MAO-BI：单胺氧化酶B型抑制剂；COMTI：儿茶酚-O-甲级转移酶抑制剂2020年指南继续强调了多学科治疗： ①坚持综合治疗，应对帕金森病的运动症状和非运动症状采取全面综合治疗；②强调多学科治疗模式，药物治疗仍为首选，并结合手术、运动与康复、心理干预等多种治疗手段；同时，提倡在临床条件允许的情况下，组建神经内科、功能神经外科、神经心理、康复乃至社区全科医生等多学科的医生团队；③明确全程管理，目前的治疗仍以改善症状为主，不能阻止病情的发展，治疗不仅立足当前，而且需长期管理，以达到长期获益。常见药物与在研新药根据传统治疗分类和在中国获批的药品，帕金森治疗药物主要有以下几种。复方左旋多巴：恩他卡朋双多巴、多巴丝肼多巴胺受体激动剂（DAs）：溴隐亭、培高利特（已撤市）、吡贝地尔、甲磺酸-a-二氢麦角隐亭、普拉克索、罗匹尼罗和罗替高汀儿茶酚-O-甲级转移酶抑制剂（COMTI）：托卡朋和恩他卡朋单胺氧化酶B型抑制剂（MAO-BI）：雷沙吉兰和司来吉兰抗胆碱药：苯甲托品、苯海索以及苯海拉明去甲肾上腺素前体：屈昔多巴神经保护剂：单唾液酸四己糖神经节苷脂钠此外，还有左旋多巴和卡比多巴，其中卡比多巴需与左旋多巴联用。帕金森领域进展较慢，从2010年至今，美国FDA批准的能用于缓解帕金森症状的新分子实体仅4款：Acadia Pharma 的5-羟色胺2A受体反向激动剂酒石酸匹莫范色林、US WorldMeds的沙非酰胺、协和发酵麒麟的A2A受体拮抗剂伊曲茶碱以及第三代强效COMTI奥匹卡朋。奥匹卡朋已有复星医药引进中国，目前正在进行临床试验。在国内进行开发的帕金森药品见下表。来源：GBI SOURCE新兴技术干细胞衍生药物治疗帕金森成为一条新的探索帕金森治疗的路径。继拜耳BlueRock之后，睿健医药成为国际第二家、国内首家提交帕金森领域多能干细胞衍生药物临床申请的公司。2022年4月28日，国家药监局受理了睿健医药自主研发的帕金森管线人源多巴胺能前体细胞注射液NouvNeu001的IND申请。临床前数据显示，通过睿健医药自研的高效化学小分子诱导功能细胞再生技术，NouvNeu001 移植入体内后可高效转化为成熟多巴胺能神经元，分泌多巴胺递质，并与体内原有神经元形成神经连接，产生综合性的治疗功能，改善帕金森症状。这类前体细胞除了能够分泌多巴胺这类递质之外，还可进一步分泌多种蛋白及小核酸来改善帕金森病灶，为移植到脑部的细胞发挥作用提供良好的“土壤”环境。企业交易活动国内对帕金森病的研究对比国际略显落后，因此一些企业开始引进海外的产品和技术。2018年1月，万邦生化（母公司复星医药）与葡萄牙公司BIAL达成合作，在中国大陆独家销售代理其帕金森病治疗药物奥吡卡朋；2020年10月，日本药企Kissei Pharmaceutical宣布已与中国生物医药公司AffaMed Therapeutics就其帕金森在研新药KDT-3594达成许可协议，Affamed Therapeutics将获得在大中华区（包括中国大陆、香港、澳门和台湾地区）和东南亚六国（包括新加坡，马来西亚，泰国，印尼，越南和菲律宾）开发和商业化KDT-3594（DAs）的独家权利;2021年4月，赛神医药与礼来达合作，获得在大中华区开发和商业化针对帕金森病α-突触核蛋白靶向疗法的权利；2022年3月，上海中泽医药与美国公司 Digestome Therapeutics达成合作，获得后者DGX-001在大中华市场的独家权利。DGX-001是一种全球首创口服治疗药物，可用于治疗精神分裂症的阴性症状和认知障碍，以及帕金森病的非运动症状；2022年3月，翼思生物与德国史达德大药厂（STADA Arzneimittel AG）子公司Brtiannia Pharmaceuticals Ltd签署了一项许可协议，获得在中国大陆、香港和澳门开发和商业其皮下注射阿扑吗啡用于帕金森病的独家权利；2023年5月，畅溪制药与美国公司Acorda Therapeutics达成合作，引进后者INBRIJA（左旋多巴吸入粉雾剂）在大中华地区（中国大陆及港澳台地区）的权利。INBRIJA已在美国和欧盟获批上市，用于正在接受左旋多巴-多巴脱羧酶抑制剂治疗的成年帕金森病患者，其在关闭期（OFF episodes）的间歇性治疗；2024年1月，斯坦福大学与先声药业达成合作研究协议，将共同推动一项神经系统领域的探索性研究，为帕金森患者研发创新疗法。帕金森发现至今，目前虽有多种可以缓解症状的疗法，但还没有一种能够延缓疾病进展或治愈疾病。未来，开发这一疾病更理想的治疗方法依然是医学领域的重要目标之一。\ | /★联系我们投稿 | 发稿 | 媒体合作▶ sylvia.hua@generalbiologic.com数据库 | 咨询服务 | 资讯追踪▶ 点击左下“阅读原文”完成表单填写点击阅读原文立即订阅相关报告

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