更新于：2024-05-01

Supranuclear Palsy, Progressive

进行性核上性麻痹

更新于：2024-05-01

基本信息

别名

Classic PSP syndrome、Classic progressive supranuclear palsy syndrome、Heterogeneous system degeneration

+ [57]

简介

A degenerative disease of the central nervous system characterized by balance difficulties; OCULAR MOTILITY DISORDERS (supranuclear ophthalmoplegia); DYSARTHRIA; swallowing difficulties; and axial DYSTONIA. Onset is usually in the fifth decade and disease progression occurs over several years. Pathologic findings include neurofibrillary degeneration and neuronal loss in the dorsal MESENCEPHALON; SUBTHALAMIC NUCLEUS; RED NUCLEUS; pallidum; dentate nucleus; and vestibular nuclei. (From Adams et al., Principles of Neurology, 6th ed, pp1076-7)

关联

项与进行性核上性麻痹相关的药物

Flortaucipir F-18

靶点

TAU

作用机制

TAU调节剂

在研机构

Avid Radiopharmaceuticals, Inc.

原研机构

Siemens Healthineers AG

在研适应症

阿尔茨海默症

非在研适应症

失语 [+8]

最高研发阶段批准上市

首次获批国家/地区

美国

首次获批日期2020-05-28

Tertomotide hydrochloride

特托莫肽盐酸盐

靶点

TERT

作用机制

TERT抑制剂

在研机构

GemVax & KAEL Co., Ltd. [+1]

原研机构

Pharmexa A/S

在研适应症

胰腺癌 [+3]

非在研适应症

晚期胰腺腺癌 [+7]

最高研发阶段批准上市

首次获批国家/地区

韩国

首次获批日期2014-09-11

Tolfenamic Acid

托芬那酸

靶点

COX

作用机制

COX抑制剂

在研机构

NeuroTau, Inc.初创企业 [+1]

原研机构

杭州民生药业股份有限公司

在研适应症

关节炎 [+4]

非在研适应症

进行性核上性麻痹

最高研发阶段批准上市

首次获批国家/地区

中国

首次获批日期2005-07-13

234

项与进行性核上性麻痹相关的临床试验

NCT06355531 / Not yet recruiting临床2期

A Randomized, Double-blind, Placebo-controlled, Phase 2 Study to Assess the Efficacy, Safety, and Pharmacokinetics of FNP-223 (Oral Formulation) to Slow the Disease Progression of Progressive Supranuclear Palsy (PSP) (PROSPER)

PROSPER trial is a trial to assess the efficacy of FNP-223 in slowing disease progression in participants with PSP as measured by the PSP Rating Scale (PSPRS) over 52 weeks and to assess the safety and tolerability of FNP-223 for 52 weeks in participants with PSP.

开始日期2024-04-01

申办/合作机构

Ferrer Internacional SA

NCT06174948 / Not yet recruitingN/AIIT

The Use of the CUE1 Device in People With Idiopathic Parkinson's Disease and Related Disorders: A Feasibility Study

People with Parkinson's disease (PD) commonly experience a range of both motor (e.g., bradykinesia, rigidity, tremor, and postural instability) and non-motor (e.g., fatigue, psychiatric and behavioural disturbances, autonomic dysfunction, cognitive impairment, sleep dysfunction and olfactory loss) features. Currently, it is challenging to alleviate these symptoms with first-line treatment, the medications such as levodopa. The CUE1 is a non-invasive device, which is approved for sale in the UK market as a Class I low risk device. It is worn on the sternum or other part of the body such as the forearm and attaches to the skin via an adhesive patch which has been dermatologically tested and approved.
The CUE1 delivers pulsing cueing and vibrotactile stimulation to help improve symptoms in people with PD and it has shown to be effective in doing so in previous small case studies. This 9-week feasibility study aims to investigate the feasibility, safety, tolerability and effect of using the CUE1 as an intervention to improve motor and non-motor symptoms in people with PD and related movement disorders. People with clinical diagnosis of idiopathic PD and related disorders including those with progressive supranuclear palsy, multiple system atrophy, corticobasal degeneration, and vascular Parkinsonism as well as atypical dystonias and tremor disorders aged over 18 years old who have the capacity to provide a written consent form to take part in the study, will receive as intervention to wear the CUE1 device at home, on daily basis while carrying out their activities of daily living. Participants will also have to attend four face-to-face appointments of approximately half a day, at weeks -0, -3, -6 and -9 of the study to discuss how they are getting on with using the CUE1 and complete questionnaires on their symptoms, walking, balance, and movement tests as well as a participant's clinical diary.

开始日期2024-03-01

申办/合作机构

Queen Mary University of London

NCT06155942 / Not yet recruitingN/A

Early Biomarkers of Neurodegeneration in Parkinsonian Syndromes: Analysis in Very High Field (7T) Brain MRI.

Parkinson's disease (PD) is the most common degenerative Parkinson's syndrome and is linked, among other things, to the excessive accumulation of an abnormally aggregating protein, alpha-synuclein. Progressive Supranuclear Palsy (PSP) is another Parkinson's syndrome, linked, among other things, to the abnormal accumulation of the protein Tau, and expressed clinically by falls, early cognitive impairment and oculomotor disorders, not present in PD. The onset of these disorders is so gradual that differential diagnosis between the two diseases is only possible at a late stage, on average 3 to 5 years after the onset of symptoms.
To date, there is a lack of validated imaging biomarkers for diagnosing and monitoring PD and PSP. There is therefore an urgent need for the development of robust biomarkers capable of detecting neurodegeneration at an early stage, in order to aid differential diagnosis as soon as symptoms appear, and to potentially enable these patients to be included in specific therapeutic trials (as these diseases are pathophysiologically different) with potential neuroprotective effects.
The development of cutting-edge technologies such as 7T MRI, combined with optimized image processing methods, now enable non-invasive in vivo exploration and analysis of these small structures in terms of ion homeostasis (sodium), microstructure (volumetry, amount of iron and neuromelanin) and connectivity.

开始日期2024-01-15

申办/合作机构

Assistance Publique Hôpitaux de Marseille

100 项与进行性核上性麻痹相关的临床结果

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100 项与进行性核上性麻痹相关的转化医学

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0 项与进行性核上性麻痹相关的专利（医药）

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5,295

项与进行性核上性麻痹相关的文献（医药）

2024-02-23·Respiratory investigation

Current situation of management of spontaneous pneumothorax in Japan: A cross-sectional cohort study.

Article

作者: Hitoshi Igai ; Noriyoshi Sawabata ; Toshiro Obuchi ; Noriyuki Matsutani ; Kenji Tsuboshima ; Shouichi Okamoto ; Akihiro Hayashi

BACKGROUND:

Limited epidemiological information is available on spontaneous pneumothorax. To address this gap, the Japan Society for Pneumothorax and Cystic Lung Disease (JSPCLD) conducted a nationwide retrospective survey to investigate the current epidemiology of spontaneous pneumothorax in Japan.

METHODS:

In this study, we conducted a retrospective cross-sectional cohort study to demonstrate the clinical features of spontaneous pneumothorax in one year from April 2019 to March 2020, compare patient characteristics and treatment outcomes between primary (PSP) and secondary spontaneous pneumothorax (SSP), and investigate the risk factors associated with in-hospital mortality among patients with SSP.

RESULTS:

A total of 1784 patients from 28 institutions were enrolled in the study, with PSP observed in 956 cases (53.6%) and SSP in 817 cases (45.8%). The age distribution showed a biphasic peak caused by the different peaks between PSP and SSP. In-hospital mortality occurred in 42 cases (2.4%) among all patients, with 0 cases (0%) in PSP and 42 cases (5.1%) in SSP. Multivariable analyses revealed that interstitial pneumonia as an underlying disease (odds ratio: 2.4700, 95% confidence interval: 1.1100 to 5.4800, p = 0.0269), performance status≧3 (odds ratio: 7.3900, 95% confidence interval: 3.1900 to 17.2000, p < 0.0001), and lower value of serum albumin on admission (odds ratio: 0.4060, 95% confidence interval: 0.2140 to 0.7690, p = 0.0057) were significantly associated with in-hospital mortality among patients with SSP.

CONCLUSIONS:

SSP patients with poor baseline conditions are at a higher risk for in-hospital mortality. It is crucial to provide close and meticulous management for SSP patients with compromised conditions.

2024-02-18·Movement disorders clinical practice

Total Patient Delay: A Comparison of Patient and Clinician/Health System Delays in the Diagnosis of Progressive Supranuclear Palsy and Corticobasal Syndrome.

Article

作者: Diane M A Swallow ; Peter Murchie ; Carl E Counsell

BACKGROUND:

Early diagnosis in progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) is important for clinical care and key to developing successful disease-modifying agents. The patient-dependent phases of decision-making made before contact with a healthcare professional have been inadequately studied.

OBJECTIVES:

To evaluate the patient-dependent phases of decision-making from symptom onset, comparing this to clinician and/or health system delays within the overall diagnostic pathway.

METHODS:

Using the Anderson General Model of Total Patient Delay and a mixed-methods approach in participants with PSP/CBS and their caregivers recruited to the Scottish PSP and CBS cohort, we quantified and evaluated the determinants of "appraisal", "illness," and "behavioral" delay, comparing this to the clinician and/or health system delays ("treatment" delay) within the overall time from symptom onset to diagnosis.

RESULTS:

The time from index symptom onset to diagnosis was 3.26 (interquartile range [IQR] = 2.42, 4.75) years in PSP and 2.58 (IQR = 1.69, 4.08) years in CBS. Patient appraisal delay was 24 (IQR = 6, 60) weeks in PSP and 8 (IQR = 5, 24) weeks in CBS, illness delay 0 (IQR = -14, 0) weeks in PSP and 0 (IQR = -4, 0) weeks in CBS, with little perceived behavioral delay. Determinants of delay included the non-specificity of symptoms, normalization of symptoms within the context of age or normal physiological variability, and the extent of insight into new somatic symptoms.

CONCLUSIONS:

Although patient appraisal delay contributes to overall diagnostic delay in PSP/CBS, the greater proportion of overall diagnostic delay arises after contact with a healthcare professional (treatment delay).

2024-02-16·Brain sciences

Impulse Control Disorders in Parkinson's Disease and Atypical Parkinsonian Syndromes-Is There a Difference?

Article

作者: Mateusz Toś ; Anna Grażyńska ; Sofija Antoniuk ; Joanna Siuda

BACKGROUND AND OBJECTIVES:

Impulse control disorders (ICDs) are characterized by potentially harmful actions resulting from disturbances in the self-control of emotions and behavior. ICDs include disorders such as gambling, hypersexuality, binge eating, and compulsive buying. ICDs are known non-motor symptoms in Parkinson's disease (PD) and are associated primarily with the use of dopaminergic treatment (DRT) and especially dopamine agonists (DA). However, in atypical parkinsonism (APS), such as progressive supranuclear palsy (PSP) or multiple system atrophy (MSA), there are only single case reports of ICDs without attempts to determine the risk factors for their occurrence. Moreover, numerous reports in the literature indicate increased impulsivity in PSP. Our study aimed to determine the frequency of individual ICDs in APS compared to PD and identify potential factors for developing ICDs in APS.

MATERIALS AND METHODS:

Our prospective study included 185 patients with PD and 35 with APS (27 patients with PSP and 9 with MSA) hospitalized between 2020 and 2023 at the Neurological Department of University Central Hospital in Katowice. Each patient was examined using the Questionnaire for Impulsive-Compulsive Disorders in Parkinson's Disease (QUIP) to assess ICDs. Additionally, other scales were used to assess the advancement of the disease, the severity of depression, and cognitive impairment. Information on age, gender, age of onset, disease duration, and treatment used were collected from medical records and patient interviews.

RESULTS:

ICDs were detected in 23.39% of patients with PD (including binge eating in 11.54%, compulsive buying in 10.44%, hypersexuality in 8.79%, and pathological gambling in 4.40%), in one patient with MSA (hypersexuality and pathological gambling), and in 18.52% of patients with PSP (binge eating in 3.70%, compulsive buying in 7.41%, and hypersexuality in 11.11%). We found no differences in the frequency of ICDs between individual diseases (p = 0.4696). We confirmed that the use of higher doses of DA and L-dopa in patients with PD, as well as a longer disease duration and the presence of motor complications, were associated with a higher incidence of ICDs. However, we did not find any treatment effect on the incidence of ICDs in APS.

CONCLUSIONS:

ICDs are common and occur with a similar frequency in PD and APS. Well-described risk factors for ICDs in PD, such as the use of DRT or longer disease duration, are not fully reflected in the risk factors for ICDs in APS. This applies especially to PSP, which, unlike PD and MSA, is a tauopathy in which, in addition to the use of DRT, other mechanisms related to the disease, such as disorders in neuronal loops and neurotransmitter deficits, may influence the development of ICDs. Further prospective multicenter studies recruiting larger groups of patients are needed to fully determine the risk factors and mechanisms of ICD development in APS.

181

项与进行性核上性麻痹相关的新闻（医药）

2024-04-05

·药事纵横

3期临床失败，Amylyx渐冻症药主动撤市

声明：因水平有限，错误不可避免，或有些信息非最及时，欢迎留言指出。本文仅作医疗健康相关药物介绍，非治疗方案推荐（若涉及）;本文不构成任何投资建议。4月4日，Amylyx Pharmaceuticals宣布与美国食品和药物管理局（FDA）和加拿大卫生部达成协议，主动撤市治疗肌萎缩侧索硬化（ALS）成人患者的药物Relyvrio（AMX0035）。作出这一决定的主要原因是其三期临床PHOENIX的顶线数据，研究没有达到主要终点和次要终点。PHOENIX研究共招募了664例ALS患者，结果并未达到主要终点，第48周时，与安慰剂组比，AMX0035治疗组肌萎缩侧索硬化功能评定量表（ALSFRS-R）评分较基线变化不具有显著统计学差异（p=0.667）。此外，该研究也未达到患者报告的生活质量结果评估、总生存期以及慢肺活量（SVC）衡量的呼吸功能等次要终点。Relyvrio将不再适用于新患者。目前正在美国和加拿大接受治疗的患者，在咨询他们的医生后，希望继续治疗，可以过渡到免费的药物计划。在研管线作为公司发现和开发神经退行性疾病的创新治疗方案的一部分，Amylyx将继续推进两个关键项目，研究其用于Wolfram综合征和进行性核上性麻痹(PSP)的候选药物AMX0035，以及用于ALS的靶向calpain-2的反义寡核苷酸AMX0114。Amylyx 首席医疗官 Camille L. Bedrosian 医学博士说，我们将继续关注ALS，相信AMX0114在治疗ALS和其他疾病方面具有强大的潜力。钙离子依赖的中性蛋白酶-I2被认为是轴突变性过程中的关键蛋白，在已发表的研究中多次与神经丝生物学联系在一起。在我们对AMX0114的临床前研究和多个独立发表的研究中，抑制钙离子依赖的中性蛋白酶-I 2减少了细胞死亡和变性，降低了神经丝水平。我们期待在今年下半年启动AMX0114在ALS中的临床试验。此外，Amylyx还宣布将进行重组，将公司的财务资源集中在即将到来的临床里程碑上，该公司将裁员约70%。随着此次计划的开展，Amylyx预计现金跑道将延长至2026年，将专注于关键里程碑包括HELIOS (AMX0035治疗Wolfram综合征)、ORION (AMX0035治疗PSP)的临床数据，以及AMX0114治疗ALS的计划试验。Amylyx Pharmaceuticals成立于2013年，是一家总部位于马萨诸塞州剑桥市的制药公司，致力于开发神经退行性疾病的潜在疗法。大约十年前，两位联合创始人 Justin Klee 和 Joshua Cohen 在还是布朗大学的本科生时构思了 Relyvrio。他们的想法是，将牛磺二醇（一种有时用于调节肝酶的补充剂）和苯丁酸钠（一种治疗儿童尿素紊乱的药物）结合起来，可以通过防止细胞中两种结构（线粒体和内质网）的功能障碍，保护大脑中的神经元免受 ALS 等疾病的损害。联合创始人Justin Klee（右）和 Joshua Cohen（左）作为唯一在售产品，Relyvrio 在 2023 年为公司带来了 3.808 亿美元的产品净收入。截至 2023 年底，该公司拥有现金 3.714 亿美元。其 2020 年的运营费用为 3970 万美元，2023 年为 3.42 亿美元。参考资料：www.amylyx.comwww.endpts.com-END-药事纵横投稿须知：稿费已上调，欢迎投稿各位朋友好，觉得本文对您有帮助，请随手点一下下方的在看，以便让你的朋友也能看到哦。

临床3期引进/卖出临床失败临床2期寡核苷酸

2024-04-04

·Firstwordpharma

Amylyx to withdraw ALS therapy Relyvrio in US, Canada

Amylyx Pharmaceuticals will withdraw Relyvrio (sodium phenylbutyrate/taurursodiol) from the US market, following through on a commitment made when the amyotrophic lateral sclerosis (ALS) therapy controversially won accelerated approval in 2022. At that time, joint CEO Justin Klee said such a move would be likely if a confirmatory study failed – the company announced last month that the PHOENIX trial was a dud.Klee, along with joint CEO Joshua Cohen, said Thursday that the decision to withdraw Relyvrio was “reached…in partnership with the stakeholders who will be impacted.” Amylyx, which will also pull the drug in Canada, where it is sold as Albrioza, noted that it will provide the therapy free of charge for those currently on treatment who want to continue.Staff losses of 70%The drugmaker will also cut around 70% of its workforce as part of a restructuring plan as it looks to prioritise resources, extending its cash runway into 2026. Amylyx is also investigating the oral, fixed-dose combination of sodium phenylbutyrate and taurursodiol - known as AMX0035 - in Wolfram syndrome and progressive supranuclear palsy (PSP). Interim data from the Phase II HELIOS trial of AMX0035 for the treatment of Wolfram syndrome are expected later this month.Meanwhile, chief medical officer Camille Bedrosian, noted that the Phase III ORION study of AMX0035 for PSP is ongoing, with “an interim analysis…now expected in mid-2025.” Amylyx has also not given up on ALS, with AMX0114, an antisense oligonucleotide targeting calpain-2, set to enter clinical studies in the second half of the year.For related analysis, read KOL Views Q&A: Leading neurologist outlines where ALS field goes next after Amylyx’s Relyvrio failure.

临床2期临床3期寡核苷酸上市批准

2024-04-04

·BioSpace

Amylyx to Pull ALS Drug Relyvrio From US, Canada Markets After Phase III Fail

Pictured: Illustration showing a neuron being destroyed/iStock, Dr_Microbe Amylyx Pharmaceuticals on Thursday announced that it has started the process of pulling its amyotrophic lateral sclerosis drug Relyvrio (sodium phenylbutyrate and taurursodiol) from the U.S. and Canadian markets and will reduce the company’s workforce by approximately 70% under a restructuring plan. Effective Thursday, Relyvrio will no longer be available for new patients. Those who are currently being treated with Relyvrio can either stay on treatment or transition into a free program, depending on their physician’s advice, according to the company. Amylyx said it will work with the FDA and Health Canada to terminate the marketing authorizations for Relyvrio in these countries. Joshua Cohen and Justin Klee, co-CEOs of Amylyx, in a statement called the withdrawal of Relyvrio a “difficult moment” for the company and for patients with amyotrophic lateral sclerosis (ALS). “The decision to remove Relyvrio from the market and provide therapy free of charge for those who wish to continue was informed by the PHOENIX trial results, engagement with regulatory authorities, and discussions with the ALS community,” Cohen and Keel said. Last month, Relyvrio failed its highly anticipated Phase III PHOENIX trial, unable to significantly improve scores in the Revised Amyotrophic Lateral Sclerosis Functional Rating Scale at 48 weeks versus placebo. Amylyx’s drug also fell short of its secondary endpoints, including slow vital capacity and self-reported health status, as measured by the Amyotrophic Lateral Sclerosis Assessment Questionnaire. Amylyx will present data from PHOENIX at the upcoming American Academy of Neurology meeting, according to Thursday’s announcement. The study’s open-label extension phase is also ongoing, and Amylyx plans to collect survival data from the trial to help inform future studies in ALS. Losing its only commercial product, Amylyx on Thursday also launched a sweeping restructuring initiative to cut costs and optimize the use of its resources, with an eye toward upcoming clinical milestones. The biotech will lay off around 70% of its employees and lower financial commitments outside of its new priority areas. Amylyx will now focus on its lead asset AMX0035—which, like Relyvrio, also contains sodium phenylbutyrate and taurursodiol—being developed for Wolfram syndrome and progressive supranuclear palsy. The biotech is also advancing the antisense oligonucleotide candidate AMX0114 in ALS. CMO Camille Bedrosian revealed in a statement that Amylyx will present Phase II data for AMX0035 in Wolfram syndrome later this month while its Phase III ORION study in progressive supranuclear palsy is set for an interim analysis in mid-2025. The biotech is also preparing to initiate a clinical trial for AMX0114 in the second half of 2024. The company restructuring and priority changes should extend Amylyx’s cash runway into 2026, according to the announcement. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. Reach out to him on LinkedIn or email him at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

临床3期寡核苷酸临床2期