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

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。在过去的十年里，我们已经看到了快速的进展，人们认识到PPS不仅本身是一种可治疗的疾病，而且还为评估治疗策略提供了理想的条件，这些治疗策略可能会对更常见的痴呆和运动障碍的治疗产生广泛的影响。在这里，我们计划利用英国的科学和组织机会，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PPS影响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）。我们将与国家研究平台合作进行发现科学和翻译，包括痴呆症研究所（DRI）、英国痴呆症平台（DPUK）和国家卫生研究所-临床研究网络和生物医学研究中心（NIHR - CRN/BRC）。此外，一些制药公司已表示愿意在这一倡议中进行合作。发展PPS研究的一个主要挑战是建立必要的基础设施，使国家网络活动和具有全国代表性的患者招募成为可能。英国慈善机构帮助建立了英国网站的骨架网络（PSPA和MSAT资助的PROSPECT-M研究），该研究已成功地证明了跨专科诊所招聘和协调的概念。制药业和大学研究人员对开发新的疾病修饰疗法的试验都很感兴趣。早期诊断将需要新的诊断标记（例如专业血液检查、脊髓液检查和病理特异性脑部扫描），这些可能是与工业界一起开发的。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、提高诊断和预后准确性以及为个性化方法开发新的轨迹模型的挑战。在我们提出的ExPRESS（早期评估、诊断和治疗帕金森综合征相关综合征）研究中，我们将把临床医生和治疗早期疾病患者的治疗师联系在一起，并与疾病慈善机构（PSP协会、MSA信托）建立合作联系。我们将与专业机构（英国神经学家协会运动障碍组，英国老年医学会运动障碍组），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）等相关的英国科研联盟联系在一起，以最大限度地发挥英国在该领域活动的科学潜力，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，并开发一种临床算法，以便早期发现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、先进的核磁共振扫描、专业的脊髓液和血液测试，以及通过智能手机应用程序提供的数字测试，将迅速提高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疾病的进展。

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.