Pre-Symptomatic Familial ALS (Pre-fALS) Study - Prelude to a Treatment Trial

症状前家族性 ALS (Pre-fALS) 研究 - 治疗试验的前奏

基本信息

  • 批准号:
    10001608
  • 负责人:
  • 金额:
    $ 55.27万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2018
  • 资助国家:
    美国
  • 起止时间:
    2018-09-15 至 2023-08-31
  • 项目状态:
    已结题

项目摘要

PROJECT SUMMARY A major challenge to therapy development efforts in the field of ALS is the relatively late stage in the course of the disease at which treatment is initiated. While the reasons for this are complex, one critically important factor is that the disease process almost certainly begins well before the earliest clinical manifestations of disease with significant loss of motor neurons by the time of symptom onset, and even more so by the time of diagnosis (which is typically made about a year after symptom onset). We have long championed the idea that an early therapeutic, or even a preventative, trial would offer much greater likelihood of success and could be undertaken in people at risk for ALS. In contemplating such a trial, however, we recognized that too little was known about the pre-symptomatic phase of ALS, including elements critical to trial design. This prompted us to initiate (in 2007) Pre-fALS (Pre-Symptomatic Familial ALS), a longitudinal natural history and biomarker study of pre-symptomatic individuals who are carriers of an ALS-associated gene mutation; they are currently the only known population at risk for ALS and in whom a study of pre-symptomatic disease may be considered. Over the course of the last 10 years, we have developed and refined methods for screening and enrolling individuals who may be at risk for developing ALS; providing pre-symptomatic genetic counseling and testing; and maintaining longitudinal follow-up with minimal loss to follow-up. In so doing, we have gradually expanded the Pre-fALS cohort to include 113 gene-positive individuals and have accumulated a total of ~447 person- years follow-up; 14 of these individuals have progressed to clinically manifest disease, yielding an estimated average two-year phenoconversion rate of ~10%. With significant preliminary data in hand and the operational infrastructure now in place, we are poised to expand the Pre-fALS cohort, significantly extend cumulative follow-up time and can expect to observe a total of ~45 phenoconversion events by the end of the grant cycle. Employing a multi-modal array of evaluative procedures that includes both ‘wet’ and ‘dry’ biomarkers which permit quantification of subclinical signs of disease, we will address two very specific questions that are fundamental to the design of a future disease prevention trial. First, we will determine whether it is possible to identify a subset of people at genetic risk for ALS who are at a sufficiently high-short term risk of developing disease that a reduction in risk could be used to adequately power a disease prevention trial. Second, we will quantify longitudinal trajectories of pre-symptomatic biomarkers to determine whether changes in these biomarkers could be used to quantify the biological impact of an experimental therapeutic in a disease prevention trial. These data and the insights we glean into the pre-symptomatic stage of disease, will enable us to design and implement a disease prevention or early intervention trial in the near future that could utilize whatever therapeutic agent(s) hold the most promise at the time we are ready to initiate a groundbreaking trial of this sort. SOD1 and C9orf72 antisense oligonucleotides are likely early experimental therapeutic candidates.
项目总结

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

Michael Benatar其他文献

Michael Benatar的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('Michael Benatar', 18)}}的其他基金

Multi-Center ALS Biomarker Validation Study (CReATe Biomarkers)
多中心 ALS 生物标志物验证研究 (CReATe Biomarkers)
  • 批准号:
    10410344
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
University of Miami NeuroNEXT Trial Site
迈阿密大学 NeuroNEXT 试验网站
  • 批准号:
    10201771
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
Multi-Center ALS Biomarker Validation Study (CReATe Biomarkers)
多中心 ALS 生物标志物验证研究 (CReATe Biomarkers)
  • 批准号:
    10612967
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
University of Miami NeuroNEXT Trial Site
迈阿密大学 NeuroNEXT 试验网站
  • 批准号:
    10593638
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
University of Miami NeuroNEXT Trial Site
迈阿密大学 NeuroNEXT 试验网站
  • 批准号:
    9980517
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
Pre-Symptomatic Familial ALS (Pre-fALS) Study - Prelude to a Treatment Trial
症状前家族性 ALS (Pre-fALS) 研究 - 治疗试验的前奏
  • 批准号:
    10237152
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
Clinical Centers for the NINDS NeuroNEXT(Network of Excellence in Neuroscience Clinical Trials) Consortium
NINDS NeuroNEXT(神经科学临床试验卓越网络)联盟的临床中心
  • 批准号:
    10744345
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
Pre-Symptomatic Familial ALS (Pre-fALS) Study - Prelude to a Treatment Trial
症状前家族性 ALS (Pre-fALS) 研究 - 治疗试验的前奏
  • 批准号:
    10469619
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
Multi-Center ALS Biomarker Validation Study (CReATe Biomarkers)
多中心 ALS 生物标志物验证研究 (CReATe Biomarkers)
  • 批准号:
    9923007
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:
Pre-Symptomatic Familial ALS (Pre-fALS) Study - Prelude to a Treatment Trial; Administrative Supplement
症状前家族性 ALS (Pre-fALS) 研究 - 治疗试验的前奏;
  • 批准号:
    10363844
  • 财政年份:
    2018
  • 资助金额:
    $ 55.27万
  • 项目类别:

相似海外基金

Amyotrophic Lateral Sclerosis: treating the circuit behind the disease
肌萎缩侧索硬化症:治疗疾病背后的回路
  • 批准号:
    MR/Y014901/1
  • 财政年份:
    2024
  • 资助金额:
    $ 55.27万
  • 项目类别:
    Research Grant
Dysregulation of RNA processing as a driver of motor neuron dysfunction in Amyotrophic Lateral Sclerosis
RNA 加工失调是肌萎缩侧索硬化症运动神经元功能障碍的驱动因素
  • 批准号:
    MR/Y014286/1
  • 财政年份:
    2024
  • 资助金额:
    $ 55.27万
  • 项目类别:
    Research Grant
Fasciculation IN Amyotrophic Lateral Sclerosis Using MUMRI (FINALSUM)
使用 MUMRI 治疗肌萎缩侧索硬化症的肌束颤动 (FINALSUM)
  • 批准号:
    MR/Y503502/1
  • 财政年份:
    2024
  • 资助金额:
    $ 55.27万
  • 项目类别:
    Research Grant
I-Corps: Developing A Blood-Based Biomarker for the Detection and Monitoring of Amyotrophic Lateral Sclerosis
I-Corps:开发一种基于血液的生物标志物,用于检测和监测肌萎缩侧索硬化症
  • 批准号:
    2317745
  • 财政年份:
    2023
  • 资助金额:
    $ 55.27万
  • 项目类别:
    Standard Grant
Development of CM-CS1 CAR Treg to Treat Amyotrophic Lateral Sclerosis (ALS)
开发 CM-CS1 CAR Treg 治疗肌萎缩侧索硬化症 (ALS)
  • 批准号:
    10696512
  • 财政年份:
    2023
  • 资助金额:
    $ 55.27万
  • 项目类别:
Targeted immunotherapy for amyotrophic lateral sclerosis and frontotemporal dementia
肌萎缩侧索硬化症和额颞叶痴呆的靶向免疫治疗
  • 批准号:
    10759808
  • 财政年份:
    2023
  • 资助金额:
    $ 55.27万
  • 项目类别:
Metrics for Brain Controlled Communication: A comprehensive review of clinical outcome assessments for communication brain computer interfaces in amyotrophic lateral sclerosis
脑控制通信指标:肌萎缩侧索硬化症通信脑机接口临床结果评估的全面综述
  • 批准号:
    10848139
  • 财政年份:
    2023
  • 资助金额:
    $ 55.27万
  • 项目类别:
Resolving the Role of Neuronal STING in Amyotrophic Lateral Sclerosis and Frontotemporal Dementia
解决神经元 STING 在肌萎缩侧索硬化症和额颞叶痴呆中的作用
  • 批准号:
    10606865
  • 财政年份:
    2023
  • 资助金额:
    $ 55.27万
  • 项目类别:
The biochemical stratification of amyotrophic lateral sclerosis
肌萎缩侧索硬化症的生化分层
  • 批准号:
    MR/Y001095/1
  • 财政年份:
    2023
  • 资助金额:
    $ 55.27万
  • 项目类别:
    Fellowship
The Gut Microbiota as a Contributor to Sexual Dimorphism in Amyotrophic Lateral Sclerosis
肠道微生物群是肌萎缩侧索硬化症性别二态性的一个促成因素
  • 批准号:
    488892
  • 财政年份:
    2023
  • 资助金额:
    $ 55.27万
  • 项目类别:
    Operating Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了