TY - JOUR
T1 - Safety and Feasibility of Research Lumbar Puncture in Huntington's Disease
T2 - The HDClarity Cohort and Bioresource
AU - Rodrigues, Filipe B.
AU - Owen, Gail
AU - Sathe, Swati
AU - Pak, Elena
AU - Kaur, Dipinder
AU - Ehrhardt, Anka G.
AU - Lifer, Sherry
AU - Townhill, Jenny
AU - Schubert, Katarzyna
AU - Leavitt, Blair R.
AU - Guttman, Mark
AU - Bang, Jee
AU - Lewerenz, Jan
AU - Levey, Jamie
AU - Sampaio, Cristina
AU - Wild, Edward J.
N1 - Funding Information:
Hoffman-La Roche Ltd. JLew is an employee of the Ulm University medical center. JLew received grants from the Bundesministerium for Bildung und Forschung (BMBF, German ministry for education and research) and the European Huntington’s disease network (EHDN) during the conduct of the study. JLew is member of the extended board of the Deutsche Gesellschaft für Liquordiagnostik und klinische Neurochemie (German society for cerebrospinal fluid diagnostics and clinical neurochemistry), has received funds as compensation for conducting clinical trials for UCB Biosciences, Mar-inus Pharmaceutical, and CHDI, received speaker’s honoraria by TEVA Pharmaceuticals, CHDI, and the Movement Disorders Society. CS has received consultancy honoraria from from vTv Therapeutics, Pinteon Therapeutics, Kyowa Kirin, Pfizer, The Green Valley Pharmaceuticals, and Neuraly.
Funding Information:
The HDClarity Investigators are Edward J Wild, Mark Guttman, Blair Roland Leavitt, Ralf Reilmann, FBR, GO, KS, and EJW are University College London employees. FBR has provided consultancy services to GLG and F. Hoffmann-La Roche Ltd. EJW reports grants from Medical Research Council, CHDI Foundation, and F. Hoffmann-La Roche Ltd during the conduct of the study; personal fees from Hoffman La Roche Ltd, Triplet Therapeutics, PTC Therapeutics, Shire Therapeutics, Wave Life Sciences, Mitoconix, Takeda, and Loqus23. All honoraria for these consultancies were paid through the offices of UCL Consultants Ltd., a wholly owned subsidiary of University College London. University College London Hospitals NHS Foundation Trust has received funds as compensation for conducting clinical trials for Ionis Pharmaceuticals, Pfizer, and Teva Pharmaceuticals. SS, EP, AGE, DK, SL, JLev, and CS derive their compensation from CHDI Management/CHDI Foundation. JT is employed by the Enroll-HD platform. BRL reports related research grant funding from Canadian Institutes of Health Research, CHDI Foundation, Weston Foundation, the Huntington Society of Canada, uniQure, Teva, and Roche during the conduct of the study; Paid scientific consultancies from Ionis Pharmaceuticals, Roche, Triplet Therapeutics, PTC Therapeutics, Novartis, Teva, Mitoconix, Takeda, and uniQure; and the Centre for HD at UBC Hospital has received funding to conduct clinical trials in HD from CHDI, Ionis Pharmaceuticals, Roche, Vaccinex, and Teva Pharmaceuticals via the HSG. MG has provided consultancy services to F. Hoffmann-La Roche Ltd, Novartis, PTC Therapeutics, and CHDI Foundation. Research support from Hoffmann-La Roche, Ltd, Wave Life Sciences, Triplet Therapeutics, Neurocrine Biosciences, and CHDI Foundation Inc. JB has served on the Scientific Advisory Board for WAVE and has provided consultancy services to F.
Publisher Copyright:
© 2022-IOS Press. All rights reserved.
PY - 2022
Y1 - 2022
N2 - Background: Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington's disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain. Objective: To investigate the safety and feasibility of research lumbar punctures (LP) in HD. Methods: HDClarity is an ongoing international biofluid collection initiative built on the Enroll-HD platform, where clinical assessments are recorded. It aims to recruit 1,200 participants. Biosamples are collected following an overnight fast: Blood via venipuncture and CSF via LP. Participants are healthy controls and HD gene expansion carriers across the disease spectrum. We report on monitored data from February 2016 to September 2019. Results: Of 448 participants screened, 398 underwent at least 1 sampling visit, of which 98.24% were successful (i.e., CSF was collected), amounting to 10,610 mL of CSF and 8,200 mL of plasma. In the total 572 sampling visits, adverse events were reported in 24.13%, and headaches of any kind and post-LP headaches in 14.86% and 12.24%, respectively. Frequencies were less in manifest HD; gender, age, body mass index and disease burden score were not associated with the occurrence of the events in gene expansion carriers. Headaches and back pain were the most frequent adverse events. Conclusion: HDClarity is the largest CSF collection initiative to support scientific research into HD and is now stablished as a leading resource for HD research. Our data confirm that research LP in HD are feasible and acceptable to the community, and have a manageable safety profile.
AB - Background: Biomarkers are needed to monitor disease progression, target engagement and efficacy in Huntington's disease (HD). Cerebrospinal fluid (CSF) is an ideal medium to research such biomarkers due to its proximity to the brain. Objective: To investigate the safety and feasibility of research lumbar punctures (LP) in HD. Methods: HDClarity is an ongoing international biofluid collection initiative built on the Enroll-HD platform, where clinical assessments are recorded. It aims to recruit 1,200 participants. Biosamples are collected following an overnight fast: Blood via venipuncture and CSF via LP. Participants are healthy controls and HD gene expansion carriers across the disease spectrum. We report on monitored data from February 2016 to September 2019. Results: Of 448 participants screened, 398 underwent at least 1 sampling visit, of which 98.24% were successful (i.e., CSF was collected), amounting to 10,610 mL of CSF and 8,200 mL of plasma. In the total 572 sampling visits, adverse events were reported in 24.13%, and headaches of any kind and post-LP headaches in 14.86% and 12.24%, respectively. Frequencies were less in manifest HD; gender, age, body mass index and disease burden score were not associated with the occurrence of the events in gene expansion carriers. Headaches and back pain were the most frequent adverse events. Conclusion: HDClarity is the largest CSF collection initiative to support scientific research into HD and is now stablished as a leading resource for HD research. Our data confirm that research LP in HD are feasible and acceptable to the community, and have a manageable safety profile.
KW - biomarkers
KW - blood
KW - cerebrospinal fluid
KW - cohort studies
KW - Huntington's disease
KW - spinal puncture
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UR - http://www.scopus.com/inward/citedby.url?scp=85125851649&partnerID=8YFLogxK
U2 - 10.3233/JHD-210508
DO - 10.3233/JHD-210508
M3 - Article
C2 - 35253773
AN - SCOPUS:85125851649
SN - 1879-6397
VL - 11
SP - 59
EP - 69
JO - Journal of Huntington's Disease
JF - Journal of Huntington's Disease
IS - 1
ER -