Early assessment, diagnosis and treatment of Parkinson's Plus Related Syndromes (ExPRESS)

帕金森氏附加相关综合征的早期评估、诊断和治疗 (ExPRESS)

• 批准号: MR/Y008219/1
• 负责人: Huw Morris
• 金额: $ 170.25万
• 依托单位: University College London
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=MR%2FY008219%2F1
• 关键词: Early; assessment; diagnosis; treatment; Parkinson

Progressive supranuclear palsy (PSP), Multiple System Atrophy (MSA) and Corticobasal syndrome (CBS) are rare brain disorders, which cause rapidly progressive disability. The last decade has seen rapid progress and recognition that PPS are not only tractable disorders in their own right, but also provide ideal conditions in which to evaluate therapeutic strategies which will potentially have a wide impact in the treatment of more common dementias and movement disorders. Here, we plan to build on scientific and organisational opportunities in the UK, to improve early diagnosis and treatment for PPS. We will do so in partnership with the NHS and a network of collaborating clinicians, and charities supporting families affected by PPS including the Progressive Supranuclear Palsy Association (PSPA) and Multiple System Atrophy Trust (MSAT). We will engage with national research platforms for discovery science and translation, including the Dementia Research Institute (DRI), Dementia Platform UK (DPUK), and National Institute for Health Research - Clinical Research Network and Biomedical Research Centres (NIHR - CRN/BRC). In addition, a number of drug companies have indicated that they would like to collaborate in this initiative. A major challenge for the development of PPS research has been to build the infrastructure required to enable national network activities and nationally-representative patient recruitment. UK charities helped to establish a skeleton network of UK sites (the PSPA and MSAT funded PROSPECT-M study), which has been successful in proof-of-concept for recruitment and coordination across specialist clinics. There is significant interest from both pharmaceutical industry and university researchers in developing new trials of disease modifying therapies. Early diagnosis will require new diagnostic markers (for example specialist blood tests, spinal fluid tests, and pathology-specific brain scans), likely developed with industry. To maximise the impact of forthcoming trials, we need to meet the challenge of recruiting patients with early stage disease, improving diagnostic and prognostic accuracy and developing new trajectory models for individualised approaches. Within our proposed ExPRESS (Early assessment, diagnosis and treatment of Parkinson's Plus Related Syndromes) study we will link together clinicians and therapists who see patients with early stage disease and establish collaborative links with disease charities (PSP Association, MSA Trust). We will link together with professional bodies (Association of British Neurologists Movement Disorders Group, British Geriatric Society Movement Disorders Group), industry partners, and linked UK scientific research consortia such as the UK Dementia Research Institute (DRI), Dementia Platform UK (DPUK), UK Brain Bank Network (BBN) and Health Data Research UK (HDRUK) to maximise the scientific potential of the UK's activity in this area and to improve the potential to develop new treatments.We will recruit patients who have been referred from primary care with suspected Parkinson's disease and develop a clinical algorithm which will enable early detection and recruitment of patients likely to have Parkinson's Plus Syndromes (PPS). This will improve clinical diagnostic pathways and early disease diagnosis. However, we envisage that emerging technologies such as protein based brain scans, advanced MRI scans, specialist spinal fluid and blood tests, and digital tests, for example delivered through smartphone apps, will rapidly accelerate our ability to identify patients with these rare movement disorders. Ultimately, we hope that these early stage patients will be recruited to clinical trials which slow down or stop the progression of these disabling conditions.

进行性核上性麻痹（PSP）、多系统萎缩（MSA）和皮质基底综合征（CBS）是罕见的脑部疾病，可导致快速进行性残疾。在过去的十年中，PPS不仅是自身易于处理的疾病，而且还提供了评估治疗策略的理想条件，这些治疗策略可能对更常见的痴呆和运动障碍的治疗产生广泛影响。在这里，我们计划在英国建立科学和组织的机会，以改善PPS的早期诊断和治疗。我们将与NHS和合作临床医生网络以及支持受PPS影响的家庭的慈善机构合作，包括进行性核上性麻痹协会（PSPA）和多系统萎缩信托基金（MSAT）。我们将与发现科学和翻译的国家研究平台合作，包括痴呆症研究所（DRI），英国痴呆症平台（DPUK）和国家健康研究所-临床研究网络和生物医学研究中心（NIHR - CRN/BRC）。此外，一些制药公司表示愿意在这一倡议中进行合作。PPS研究发展的一个主要挑战是建立必要的基础设施，以实现国家网络活动和具有全国代表性的患者招募。英国慈善机构帮助建立了一个英国网站的骨架网络（PSPA和MSAT资助的PROSPECT-M研究），该研究在专家诊所的招聘和协调方面取得了成功。制药业和大学研究人员对开发疾病改善疗法的新试验都有很大的兴趣。早期诊断将需要新的诊断标志物（例如专家血液测试，脊髓液测试和病理学特定的脑部扫描），可能与工业发展。为了最大限度地发挥即将进行的试验的影响，我们需要应对招募早期疾病患者的挑战，提高诊断和预后的准确性，并为个性化方法开发新的轨迹模型。在我们提出的ExPRESS（帕金森氏综合征相关Syndrome的早期评估，诊断和治疗）研究中，我们将把临床医生和治疗师联系在一起，他们看到早期疾病患者，并与疾病慈善机构（PSP协会，MSA信托）建立合作关系。我们将与专业机构联系在一起（英国神经学家协会运动障碍组，英国老年学会运动障碍组），行业合作伙伴，以及英国痴呆症研究所（DRI），英国痴呆症平台（DPUK），英国脑库网络（BBN）和英国健康数据研究（HDRUK）为了最大限度地发挥英国在这一领域的科学潜力，并提高开发新疗法的潜力，我们将招募从初级保健转介的疑似帕金森病患者，研究人员正在研究帕金森综合征（PPS）的临床诊断方法，并开发一种临床算法，能够早期检测和招募可能患有帕金森综合征（PPS）的患者。这将改善临床诊断途径和早期疾病诊断。然而，我们设想新兴技术，如基于蛋白质的脑部扫描，先进的MRI扫描，专业脊髓液和血液测试以及数字测试，例如通过智能手机应用程序提供，将迅速加快我们识别这些罕见运动障碍患者的能力。最终，我们希望这些早期患者将被招募到临床试验中，以减缓或阻止这些致残性疾病的进展。

项目成果

Uncovering spatiotemporal patterns of atrophy in progressive supranuclear palsy using unsupervised machine learning.

• DOI: 10.1093/braincomms/fcad048
• 发表时间: 2023
• 期刊: Brain communications
• 影响因子: 4.8

Evaluation of cerebrospinal fluid alpha-synuclein seed amplification assay in PSP and CBS

PSP 和 CBS 中脑脊液 α-突触核蛋白种子扩增测定的评价

• DOI: 10.1101/2024.02.28.24303478
• 发表时间: 2024
• 作者: Vaughan D

The pathogenesis of Parkinson's disease

• DOI: 10.1016/s0140-6736(23)01478-2
• 发表时间: 2024-01
• 期刊: The Lancet
• 作者: Huw R Morris;M. Spillantini;Carolyn M Sue;C. Williams-Gray

Progression of atypical parkinsonian syndromes: PROSPECT-M-UK study implications for clinical trials.

• DOI: 10.1093/brain/awad105
• 发表时间: 2023-08-01
• 期刊: BRAIN
• 影响因子: 14.5
• 作者: Street, Duncan;Jabbari, Edwin;Costantini, Alyssa;Jones, P. Simon;Holland, Negin;Rittman, Timothy;Jensen, Marte T.;Chelban, Viorica;Goh, Yen Y.;Guo, Tong;Heslegrave, Amanda J.;Roncaroli, Federico;Klein, Johannes C.;Ansorge, Olaf;Allinson, Kieren S. J.;Jaunmuktane, Zane;Revesz, Tamas;Warner, Thomas T.;Lees, Andrew J.;Zetterberg, Henrik;Russell, Lucy L.;Bocchetta, Martina;Rohrer, Jonathan D.;Burn, David J.;Pavese, Nicola;Gerhard, Alexander;Kobylecki, Christopher;Leigh, P. Nigel;Church, Alistair;Hu, Michele T. M.;Houlden, Henry;Morris, Huw;Rowe, James B.
• 通讯作者: Rowe, James B.

Frequency and outcomes of gastrostomy insertion in a longitudinal cohort study of atypical parkinsonism

非典型帕金森病纵向队列研究中胃造口术插入的频率和结果

• DOI: 10.1111/ene.16258
• 发表时间: 2024
• 期刊: European Journal of Neurology
• 影响因子: 5.1
• 作者: Kobylecki C