The Frontotemporal Lobar Degeneration Clinical Research Consortium

描述(由申请人提供) 额颞叶变性(FTLD)是一组罕见的神经退行性疾病的神经病理学术语，对应于四个主要重叠的临床症状：额颞叶痴呆(FTD)、原发性进行性失语(PPA)、皮质基底膜变性综合征(CBS)和进行性核上性瘫痪综合征(PSPS)。目前还没有有效的FTLD疗法，尽管新药正在达到需要进行临床试验的阶段。这项提议的总体目标是建立一个FTLD临床研究联盟(FTLD CRC)，以支持FTLD疗法的开发。FTLD CRC的总部将设在加州大学旧金山分校，并将与六个患者倡导团体合作管理该财团。将在北美的13个临床地点对患者进行评估，遗传学核心将对所有人的FTLD相关基因进行基因分型。临床研究项目将集中在临床症状和潜在病理之间存在强烈相关性的特定FTLD综合征，这些症状将成为新试验的目标。研究项目1将使用新的FTLD评估小组收集散发性FTLD患者的横断面数据，并筛查所有个体以寻找已知的导致FTLD的突变和全身炎症的证据，为抗tau和抗炎药的试验做准备。研究项目2将收集携带MAPT、GRN和C90RF72突变的家族性FTLD(f-FTLD)个人及其无症状家庭成员的纵向临床和MRL数据，以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，为临床试验的设计和实施提供便利；2)确定针对新试验的零星FTLD的临床、遗传和全身炎症细胞因子谱：语义变异PPA、FTD合并肌萎缩侧索硬化症和PSPS；3)使用新的临床措施和一年多的磁共振成像确定无症状和有症状的f-FTLD患者的自然病史；4)获得FTLD中使用新型tau PET显像剂PBB3的试点数据，以及其他可能在未来试验中使用的新型FTLD生物标志物和临床工具；5)培训专注于FTLD治疗开发的临床研究人员。

DESCRIPTION (provided by applicant) Frontotemporal Lobar Degeneration (FTLD) is the neuropathological 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 MRl 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.