TY - JOUR
T1 - A natural history study to track brain and spinal cord changes in individuals with Friedreich's ataxia
T2 - TRACK-FA study protocol
AU - Georgiou-Karistianis, Nellie
AU - Corben, Louise A.
AU - Reetz, Kathrin
AU - Adanyeguh, Isaac M.
AU - Corti, Manuela
AU - Deelchand, Dinesh K.
AU - Delatycki, Martin B.
AU - Dogan, Imis
AU - Evans, Rebecca
AU - Farmer, Jennifer
AU - França, Marcondes C.
AU - Gaetz, William
AU - Harding, Ian H.
AU - Harris, Karen S.
AU - Hersch, Steven
AU - Joules, Richard
AU - Joers, James J.
AU - Krishnan, Michelle L.
AU - Lax, Michelle
AU - Lock, Eric F.
AU - Lynch, David
AU - Mareci, Thomas
AU - Muthuhetti Gamage, Sahan
AU - Pandolfo, Massimo
AU - Papoutsi, Marina
AU - Rezende, Thiago J.R.
AU - Roberts, Timothy P.L.
AU - Rosenberg, Jens T.
AU - Romanzetti, Sandro
AU - Schulz, Jörg B.
AU - Schilling, Traci
AU - Schwarz, Adam J.
AU - Subramony, Sub
AU - Yao, Bert
AU - Zicha, Stephen
AU - Lenglet, Christophe
AU - Henry, Pierre Gilles
N1 - Publisher Copyright:
Copyright: © 2022 Georgiou-Karistianis et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
PY - 2022
Y1 - 2022
N2 - INTRODUCTION: Drug development for neurodegenerative diseases such as Friedreich's ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA. METHODS: 200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich's Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers. DISCUSSION: Prioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression. CLINICAL TRIAL REGISTRATION: ClinicalTrails.gov Identifier: NCT04349514.
AB - INTRODUCTION: Drug development for neurodegenerative diseases such as Friedreich's ataxia (FRDA) is limited by a lack of validated, sensitive biomarkers of pharmacodynamic response in affected tissue and disease progression. Studies employing neuroimaging measures to track FRDA have thus far been limited by their small sample sizes and limited follow up. TRACK-FA, a longitudinal, multi-site, and multi-modal neuroimaging natural history study, aims to address these shortcomings by enabling better understanding of underlying pathology and identifying sensitive, clinical trial ready, neuroimaging biomarkers for FRDA. METHODS: 200 individuals with FRDA and 104 control participants will be recruited across seven international study sites. Inclusion criteria for participants with genetically confirmed FRDA involves, age of disease onset ≤ 25 years, Friedreich's Ataxia Rating Scale (FARS) functional staging score of ≤ 5, and a total modified FARS (mFARS) score of ≤ 65 upon enrolment. The control cohort is matched to the FRDA cohort for age, sex, handedness, and years of education. Participants will be evaluated at three study visits over two years. Each visit comprises of a harmonized multimodal Magnetic Resonance Imaging (MRI) and Spectroscopy (MRS) scan of the brain and spinal cord; clinical, cognitive, mood and speech assessments and collection of a blood sample. Primary outcome measures, informed by previous neuroimaging studies, include measures of: spinal cord and brain morphometry, spinal cord and brain microstructure (measured using diffusion MRI), brain iron accumulation (using Quantitative Susceptibility Mapping) and spinal cord biochemistry (using MRS). Secondary and exploratory outcome measures include clinical, cognitive assessments and blood biomarkers. DISCUSSION: Prioritising immediate areas of need, TRACK-FA aims to deliver a set of sensitive, clinical trial-ready neuroimaging biomarkers to accelerate drug discovery efforts and better understand disease trajectory. Once validated, these potential pharmacodynamic biomarkers can be used to measure the efficacy of new therapeutics in forestalling disease progression. CLINICAL TRIAL REGISTRATION: ClinicalTrails.gov Identifier: NCT04349514.
UR - http://www.scopus.com/inward/record.url?scp=85142388068&partnerID=8YFLogxK
U2 - 10.1371/journal.pone.0269649
DO - 10.1371/journal.pone.0269649
M3 - Article
C2 - 36410013
AN - SCOPUS:85142388068
VL - 17
JO - PLoS ONE
JF - PLoS ONE
SN - 1932-6203
IS - 11
M1 - e0269649
ER -