New directions in clinical trials for frontotemporal lobar degeneration: Methods and outcome measures

被引：46

作者：

Boxer, Adam L. ^{[1
]}

Gold, Michael ^{[2
]}

Feldman, Howard ^{[3
]}

Boeve, Bradley F. ^{[4
]}

Dickinson, Susan L. -J. ^{[5
]}

Fillit, Howard ^{[6
]}

Ho, Carole ^{[7
]}

Paul, Robert ^{[8
]}

Pearlman, Rodney ^{[9
]}

Sutherland, Margaret ^{[10
]}

Verma, Ajay ^{[11
]}

Arneric, Stephen P. ^{[12
]}

Alexander, Brian M. ^{[13
]}

Dickerson, Bradford C. ^{[14
]}

Dorsey, Earl Ray ^{[15
]}

Grossman, Murray ^{[16
]}

Huey, Edward D. ^{[17
,18
]}

Irizarry, Michael C. ^{[19
]}

Marks, William J. ^{[20
]}

Masellis, Mario ^{[21
,22
]}

McFarland, Frances ^{[23
]}

Niehoff, Debra ^{[5
]}

Onyike, Chiadi U. ^{[24
]}

Paganoni, Sabrina ^{[25
]}

Panzara, Michael A. ^{[26
]}

Rockwood, Kenneth ^{[27
]}

Rohrer, Jonathan D. ^{[28
]}

Rosen, Howard ^{[1
]}

Schuck, Robert N. ^{[29
]}

Soares, Holly D. ^{[30
]}

Tatton, Nadine ^{[5
]}

机构：

[1] Univ Calif San Francisco, Dept Neurol, Memory & Aging Ctr, San Francisco, CA 94143 USA

[2] AbbVie, Dept Neurosci, Chicago, IL USA

[3] Univ Calif San Diego, Dept Neurosci, San Diego, CA 92103 USA

[4] Mayo Clin, Dept Neurol, Rochester, MN USA

[5] Assoc Frontotemporal Degenerat, Radnor, PA USA

[6] Alzheimers Drug Discovery Fdn, New York, NY USA

[7] Denali Therapeut, San Francisco, CA USA

[8] Alector Inc, San Francisco, CA USA

[9] Bluefield Project, San Francisco, CA USA

[10] Chan Zuckerberg Initiat, Redwood City, CA USA

[11] United Neurosci, Dublin, Ireland

[12] Crit Path Inst, Tucson, AZ USA

[13] Harvard Univ, Dana Farber Canc Inst, Boston, MA 02115 USA

[14] Massachusetts Gen Hosp, Dept Neurol, Boston, MA 02114 USA

[15] Univ Rochester, Ctr Hlth & Technol, Rochester, NY USA

[16] Univ Penn, Dept Neurol, Philadelphia, PA 19104 USA

[17] Columbia Univ, Dept Psychiat, New York, NY 10027 USA

[18] Columbia Univ, Dept Neurol, New York, NY 10027 USA

[19] Eli Lilly, Early Phase Neurosci, Indianapolis, IN USA

[20] Verily Life Sci, Clin Neurol, San Francisco, CA USA

[21] Univ Toronto, Sunnybrook Res Inst, Hurvitz Brain Sci Res Program, Toronto, ON, Canada

[22] Univ Toronto, Sunnybrook Hlth Sci Ctr, Dept Med Neurol, Toronto, ON, Canada

[23] McFarland Writing, Annapolis, MD USA

[24] Johns Hopkins Univ, Dept Geriatr Psychiat & Neuropsychiat, Baltimore, MD USA

[25] Massachusetts Gen Hosp, Healey Ctr ALS, Boston, MA 02114 USA

[26] Wave Life Sci, Dev, Boston, MA USA

[27] Dalhousie Univ, Div Geriatr Med, Halifax, NS, Canada

[28] UCL Inst Neurol, Dementia Res Ctr, Queen Sq, London, England

[29] US FDA, Off Clin Pharmacol, Ctr Drug Evaluat & Res, Silver Spring, MD USA

[30] AbbVie, Dept Neurol, Chicago, IL USA

来源：

ALZHEIMERS & DEMENTIA | 2020年 / 16卷 / 01期

关键词：

ARTFL; Biomarker; C9orf72; Clinical trial; Frontotemporal dementia; Frontotemporal lobar degeneration; FTD; FTLD; GRN; LEFFTDS; MAPT; Primary progressive aphasia; Progressive supranuclear palsy; PROGRESSIVE SUPRANUCLEAR PALSY; NEUROFILAMENT LIGHT-CHAIN; CEREBROSPINAL-FLUID BIOMARKERS; AMYOTROPHIC-LATERAL-SCLEROSIS; ALZHEIMERS-DISEASE; BEHAVIORAL VARIANT; DOUBLE-BLIND; DIAGNOSTIC-CRITERIA; DEMENTIA RESEARCH; GOAL ATTAINMENT;

D O I：

10.1016/j.jalz.2019.06.4956

中图分类号：

R74 [神经病学与精神病学];

学科分类号：

摘要：

Introduction: Frontotemporal lobar degeneration (FTLD) is the most common form of dementia for those under 60 years of age. Increasing numbers of therapeutics targeting FTLD syndromes are being developed. Methods: In March 2018, the Association for Frontotemporal Degeneration convened the Frontotemporal Degeneration Study Group meeting in Washington, DC, to discuss advances in the clinical science of FTLD. Results: Challenges exist for conducting clinical trials in FTLD. Two of the greatest challenges are (1) the heterogeneity of FTLD syndromes leading to difficulties in efficiently measuring treatment effects and (2) the rarity of FTLD disorders leading to recruitment challenges. Discussion: New personalized endpoints that are clinically meaningful to individuals and their families should be developed. Personalized approaches to analyzing MRI data, development of new fluid biomarkers and wearable technologies will help to improve the power to detect treatment effects in FTLD clinical trials and enable new, clinical trial designs, possibly leveraged from the experience of oncology trials. A computational visualization and analysis platform that can support novel analyses of combined clinical, genetic, imaging, biomarker data with other novel modalities will be critical to the success of these endeavors.

引用

页码：131 / 143

页数：13

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