The Frontotemporal Lobar Degeneration Clinical Research Consortium

额颞叶变性（FTLD）是一种神经病理学术语， 神经退行性疾病对应于四种主要的重叠临床综合征：额颞 痴呆（FTD）、原发性进行性失语（PPA）、皮质基底节变性综合征（CBS）和 进行性核上性麻痹综合征（PSPS）。目前没有有效的FTLD疗法， 虽然新药已经到了需要临床试验的阶段。这个项目的首要目标是 建议建立FTLD临床研究联盟（FTLD CRC），以支持FTLD的发展 治疗FTLD CRC将总部设在UCSF，并将与六个患者倡导团体合作 来管理财团患者将在北美的13个临床研究中心接受评估， 遗传学核心将对所有个体进行FTLD相关基因的基因分型。临床研究项目将集中在 临床综合征与基础疾病之间存在强相关性的特定FTLD综合征 病理学，谁是新的试验招募的目标。研究项目1将收集横截面数据 在散发性FTLD患者中使用新的FTLD评估组合，以及筛查所有个体， 已知的引起FTLD的突变和全身炎症的证据，以准备抗tau和 抗炎剂。研究项目2将收集家族性FTLD的纵向临床和MRI数据 携带MAPT、GRN和C90 RF 72突变的f-FTLD个体及其无症状家族 成员能够进行疾病预防临床试验。我们的具体目标是：1）建立FTLD临床试验 网络，以促进临床试验的设计和进行，2）确定临床，遗传和系统 针对新试验的散发性FTLD的炎症细胞因子谱：语义变体PPA、FTD和 肌萎缩侧索硬化症和PSPS; 3）确定无症状和有症状的自然史 f-FTLD患者使用新的临床措施和MR成像超过一年; 4）使用 新的tau PET显像剂PBB 3在FTLD中，以及其他新的FTLD生物标志物和临床工具， 在未来的试验中使用; 5）培训临床研究人员专注于FTLD治疗开发。

Frontotemporal Lobar Degeneration (FTLD) is the neuropathologicai term for a collection of rare neurodegenerative diseases that correspond to four main overlapping clinical syndromes: frontotemporal dementia (FTD), primary progressive aphasia (PPA), corticobasal degeneration syndrome (CBS) and progressive supranuclear palsy syndrome (PSPS). There are currently no effective FTLD therapies, although new drugs are reaching the stage where clinical trials are warranted. The overarching goal of this proposal is to build a FTLD clinical research consortium (FTLD CRC) to support the development of FTLD therapies. The FTLD CRC will be headquartered at UCSF and will partner with six patient advocacy groups to manage the consortium. Patients will be evaluated at 13 clinical sites throughout North America, and a genetics core will genotype all individuals for FTLD associated genes. Clinical research projects will focus on specific FTLD syndromes where there is a strong correlation between clinical syndrome and underlying pathology, who are targeted for enrollment in new trials. Research Project 1 will collect cross-sectional data in sporadic FTLD patients using a new FTLD assessment battery, as well as screening all individuals for known FTLD-causing mutations and evidence of systemic inflammation, to prepare for trials of anti-tau and anti-inflammatory agents. Research Project 2 will collect longitudinal clinical and MRI data on familial FTLD (f-FTLD) individuals who carry mutations in MAPT, GRN and C90RF72 and their asymptomatic family members to enable disease prevention clinical trials. Our specific aims are to: 1) build a FTLD clinical trials network to facilitate the design and conduct of clinical trials, 2) determine the clinical, genetic and systemic inflammatory cytokine profile of sporadic FTLD targeted for new trials: semantic variant PPA, FTD with amyotrophic lateral sclerosis and PSPS; 3) determine the natural history of asymptomatic and symptomatic f-FTLD patients using novel clinical measures and MR imaging over one year; 4) obtain pilot data using the new tau PET imaging agent PBB3 in FTLD, and other novel FTLD biomarkers and clinical tools that may be employed in future trials; 5) train clinical researchers focused on FTLD therapeutic development.