Spinocerebellar ataxia clinical trials: opportunities and challenges.
Journal
Annals of clinical and translational neurology
ISSN: 2328-9503
Titre abrégé: Ann Clin Transl Neurol
Pays: United States
ID NLM: 101623278
Informations de publication
Date de publication:
07 2021
07 2021
Historique:
revised:
02
04
2021
received:
19
01
2021
accepted:
05
04
2021
pubmed:
22
5
2021
medline:
19
1
2022
entrez:
21
5
2021
Statut:
ppublish
Résumé
The spinocerebellar ataxias (SCAs) are a group of dominantly inherited diseases that share the defining feature of progressive cerebellar ataxia. The disease process, however, is not confined to the cerebellum; other areas of the brain, in particular, the brainstem, are also affected, resulting in a high burden of morbidity and mortality. Currently, there are no disease-modifying treatments for the SCAs, but preclinical research has led to the development of therapeutic agents ripe for testing in patients. Unfortunately, due to the rarity of these diseases and their slow and variable progression, there are substantial hurdles to overcome in conducting clinical trials. While the epidemiological features of the SCAs are immutable, the feasibility of conducting clinical trials is being addressed through a combination of strategies. These include improvements in clinical outcome measures, the identification of imaging and fluid biomarkers, and innovations in clinical trial design. In this review, we highlight current challenges in initiating clinical trials for the SCAs and also discuss pathways for researchers and clinicians to mitigate these challenges and harness opportunities for clinical trial development.
Identifiants
pubmed: 34019331
doi: 10.1002/acn3.51370
pmc: PMC8283160
doi:
Substances chimiques
Biomarkers
0
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
1543-1556Subventions
Organisme : NINDS NIH HHS
ID : R03 NS114871
Pays : United States
Organisme : NIH HHS
ID : 1R01NS082351
Pays : United States
Organisme : NIH HHS
ID : 1R01NS104434
Pays : United States
Organisme : NIH HHS
ID : 1R01NS118179
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS082351
Pays : United States
Organisme : NCATS NIH HHS
ID : UL1 TR001422
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS062051
Pays : United States
Organisme : NINDS NIH HHS
ID : U01 NS104326
Pays : United States
Organisme : NIH HHS
ID : R56NS108639
Pays : United States
Organisme : Biohaven Pharmaceuticals
ID : U01NS104326
Organisme : NIH HHS
ID : 1R13NS117005
Pays : United States
Organisme : NIH HHS
ID : 1R03NS114871
Pays : United States
Organisme : NINDS NIH HHS
ID : R56 NS108639
Pays : United States
Organisme : NINDS NIH HHS
ID : R13 NS117005
Pays : United States
Organisme : NIH HHS
ID : 1R01NS062051
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS118179
Pays : United States
Informations de copyright
© 2021 The Authors. Annals of Clinical and Translational Neurology published by Wiley Periodicals LLC on behalf of American Neurological Association.
Références
Nature. 2017 Apr 20;544(7650):367-371
pubmed: 28405022
Nat Med. 2014 Apr;20(4):415-8
pubmed: 24608097
Mov Disord. 2011 Mar;26(4):731-5
pubmed: 21506152
Cerebellum. 2015 Apr;14(2):128-32
pubmed: 25370748
Sci Rep. 2019 Nov 14;9(1):16872
pubmed: 31728006
Arch Neurol. 2004 Jun;61(6):933-7
pubmed: 15210534
Annu Rev Pathol. 2019 Jan 24;14:1-27
pubmed: 30089230
Eye (Lond). 2018 Jan;32(1):120-127
pubmed: 28799562
Cell. 2015 Jul 30;162(3):516-26
pubmed: 26232222
Mol Neurobiol. 2019 Sep;56(9):6106-6120
pubmed: 30721448
Tremor Other Hyperkinet Mov (N Y). 2019 Sep 26;9:
pubmed: 31632837
Elife. 2018 Dec 03;7:
pubmed: 30507379
Ann Neurol. 2018 Apr;83(4):816-829
pubmed: 29575033
Nature. 2017 Apr 20;544(7650):362-366
pubmed: 28405024
EMBO J. 2020 Jan 2;39(1):e101112
pubmed: 31721251
Parkinsonism Relat Disord. 2011 Aug;17(7):521-7
pubmed: 21600833
Dis Markers. 2015;2015:413098
pubmed: 26265793
Ann Neurol. 1996 Feb;39(2):241-55
pubmed: 8967756
J Med Genet. 2014 Jul;51(7):479-86
pubmed: 24780882
Lancet Neurol. 2015 Nov;14(11):1101-8
pubmed: 26377379
J Neurol Neurosurg Psychiatry. 1998 Apr;64(4):499-504
pubmed: 9576542
J Neurol. 2018 Aug;265(8):1740-1752
pubmed: 29427026
Am J Hum Genet. 2019 Mar 7;104(3):542-552
pubmed: 30827498
Neurology. 2006 Jun 13;66(11):1717-20
pubmed: 16769946
Clin Pharmacol Ther. 2001 Mar;69(3):89-95
pubmed: 11240971
Eur J Neurol. 2020 Mar;27(3):498-505
pubmed: 31571321
JCI Insight. 2018 Nov 2;3(21):
pubmed: 30385727
Brain. 2020 Oct 1;143(10):3041-3051
pubmed: 33029617
Mov Disord Clin Pract. 2014 Jun 12;1(4):291-298
pubmed: 30363941
Neuroimage Clin. 2018 Jun 14;19:858-867
pubmed: 29922574
Tremor Other Hyperkinet Mov (N Y). 2018 Oct 1;8:577
pubmed: 30410817
Lancet Neurol. 2013 Jul;12(7):650-8
pubmed: 23707147
Front Neurol. 2020 Aug 26;11:902
pubmed: 32982927
Cerebellum. 2016 Aug;15(4):518-25
pubmed: 26395908
Ann Clin Transl Neurol. 2018 Jan 22;5(3):297-314
pubmed: 29560375
NPJ Digit Med. 2018 Nov 23;1:64
pubmed: 31304341
Nat Rev Neurol. 2018 Oct;14(10):590-605
pubmed: 30131520
Cerebellum Ataxias. 2016 Nov 22;3:20
pubmed: 27895927
Mov Disord. 2010 Jul 15;25(9):1253-61
pubmed: 20310029
Mov Disord. 2004 Nov;19(11):1320-5
pubmed: 15390003
Nat Commun. 2016 Jun 01;7:11647
pubmed: 27248057
Mov Disord. 2013 Jul;28(8):1125-32
pubmed: 23553599
Arch Neurol. 2008 Jun;65(6):716-23
pubmed: 18413464
Lancet Neurol. 2013 Jul;12(7):637-49
pubmed: 23664844
Nat Rev Dis Primers. 2019 Apr 11;5(1):24
pubmed: 30975995
Annu Rev Neurosci. 2019 Jul 8;42:227-247
pubmed: 30909783
J Neurol Sci. 2021 May 15;424:117417
pubmed: 33836316
Neurology. 2010 Mar 9;74(10):839-45
pubmed: 20211908
Neuroimage. 2010 Jan 1;49(1):158-68
pubmed: 19631275
Arch Neurol. 2005 Aug;62(8):1280-5
pubmed: 16087769
Am J Phys Med Rehabil. 2020 Sep;99(9):795-800
pubmed: 32167956
Orphanet J Rare Dis. 2018 Oct 25;13(1):186
pubmed: 30359266
Arch Neurol. 2001 Aug;58(8):1257-63
pubmed: 11493166
Lancet Neurol. 2020 Sep;19(9):738-747
pubmed: 32822634
Front Cell Neurosci. 2019 Jan 21;12:509
pubmed: 30718999
Neurology. 2018 Mar 6;90(10):464-471
pubmed: 29440566
JAMA Neurol. 2016 Dec 1;73(12):1485-1490
pubmed: 27749953
Parkinsonism Relat Disord. 2020 Sep;78:73-78
pubmed: 32745980
Continuum (Minneap Minn). 2016 Oct;22(5, Neuroimaging):1636-1654
pubmed: 27740992
Cerebellum. 2014 Apr;13(2):199-206
pubmed: 24085647
Front Neurol. 2017 Sep 20;8:485
pubmed: 28979235
J Nucl Med. 2012 Jul;53(7):1074-80
pubmed: 22653791
Sci Transl Med. 2018 Oct 3;10(461):
pubmed: 30282695
Orphanet J Rare Dis. 2019 Feb 8;14(1):36
pubmed: 30736861
Nat Med. 2020 Mar;26(3):387-397
pubmed: 32123386
Lancet Neurol. 2017 Aug;16(8):601-609
pubmed: 28601473
N Engl J Med. 2019 Jun 13;380(24):2307-2316
pubmed: 31059641
J Nucl Med. 1998 Sep;39(9):1518-20
pubmed: 9744334
AJNR Am J Neuroradiol. 2007 Nov-Dec;28(10):1996-2000
pubmed: 17998418
Int J Mol Sci. 2019 Jun 27;20(13):
pubmed: 31252669
J Neurol. 2021 Aug;268(8):2749-2756
pubmed: 32266540
Nat Clin Pract Neurol. 2007 Mar;3(3):136-7
pubmed: 17290240
Sci Transl Med. 2020 Oct 21;12(566):
pubmed: 33087504
Int J Mol Sci. 2020 Apr 26;21(9):
pubmed: 32357546
Nat Med. 2011 Oct 16;17(11):1445-7
pubmed: 22001907
J Clin Invest. 2015 May;125(5):1979-86
pubmed: 25844897
J Biopharm Stat. 2020 May 3;30(3):537-549
pubmed: 32065047
Brain Res. 2003 Oct 10;987(1):25-31
pubmed: 14499942
J Neurol. 2018 Jul;265(7):1618-1624
pubmed: 29737427
PLoS One. 2012;7(10):e47479
pubmed: 23094053
PLoS One. 2013 Sep 20;8(9):e75091
pubmed: 24073237
Front Neurol. 2019 Oct 15;10:1094
pubmed: 31749756
Mol Neurodegener. 2019 Nov 4;14(1):39
pubmed: 31684998
Cerebellum. 2016 Aug;15(4):483-90
pubmed: 26298474
J Huntingtons Dis. 2016;5(1):1-13
pubmed: 27031730
J Neuroimaging. 2012 Jul;22(3):285-91
pubmed: 21699609
Hum Mol Genet. 2020 Aug 29;29(15):2551-2567
pubmed: 32761094
Zhong Nan Da Xue Xue Bao Yi Xue Ban. 2011 Jun;36(6):504-10
pubmed: 21743141
F1000Res. 2018 Nov 12;7:
pubmed: 30473770
Biomolecules. 2020 Mar 03;10(3):
pubmed: 32138195
Nat Rev Neurol. 2018 Oct;14(10):577-589
pubmed: 30171200
Int J Neurosci. 2014 Feb;124(2):97-101
pubmed: 23879331
Parkinsonism Relat Disord. 2020 Mar;72:37-43
pubmed: 32105964
J Neurol. 2007 Jul;254(7):838-45
pubmed: 17468965
Mutat Res. 2013 Oct 9;757(2):99-103
pubmed: 23994570
PLoS One. 2012;7(10):e47925
pubmed: 23118909
Lancet Neurol. 2015 Oct;14(10):985-91
pubmed: 26321318
Genet Med. 2013 Sep;15(9):673-83
pubmed: 23538602
Prog Neurobiol. 2017 Aug;155:194-211
pubmed: 27887908
Front Mol Neurosci. 2020 Apr 15;13:53
pubmed: 32351363
Brain Res. 2005 Jul 12;1049(2):191-202
pubmed: 15963476
Mov Disord. 2021 Feb;36(2):283-297
pubmed: 33022077
RNA Biol. 2018;15(6):707-714
pubmed: 29560813
J Nucl Med. 2000 Jun;41(6):994-8
pubmed: 10855623
J Neurol. 2019 Feb;266(2):533-544
pubmed: 30284037
Nat Rev Drug Discov. 2020 Oct;19(10):673-694
pubmed: 32782413
Neurology. 2011 Sep 13;77(11):1035-41
pubmed: 21832228
Brain. 2014 Sep;137(Pt 9):2444-55
pubmed: 24972706
Mov Disord. 2015 Apr 15;30(5):662-70
pubmed: 25773989
Epigenomics. 2019 Jul;11(9):1037-1056
pubmed: 31144508
Ann Neurol. 2004 Mar;55(3):426-30
pubmed: 14991822
Cereb Cortex. 2016 Jul;26(7):3205-18
pubmed: 26209844
Clin Chim Acta. 2005 Jan;351(1-2):143-8
pubmed: 15563883
Brain. 2004 Aug;127(Pt 8):1785-95
pubmed: 15240431
Lancet Neurol. 2010 Sep;9(9):885-94
pubmed: 20723845
J Neurochem. 2013 Aug;126 Suppl 1:118-24
pubmed: 23859347
Cerebellum. 2004;3(2):107-11
pubmed: 15233578
Neuron. 2019 Mar 6;101(5):801-819
pubmed: 30844400
Parkinsonism Relat Disord. 2011 Jun;17(5):338-42
pubmed: 21334959
Brain. 2008 May;131(Pt 5):1352-61
pubmed: 18378516
Neuroepidemiology. 2014;42(3):174-83
pubmed: 24603320
J Neuroophthalmol. 2009 Sep;29(3):227-37
pubmed: 19726947
Lancet Neurol. 2018 Apr;17(4):327-334
pubmed: 29553382
Cerebellum. 2011 Jun;10(2):208-17
pubmed: 20838948
Brain. 2013 Mar;136(Pt 3):905-17
pubmed: 23423669
Brain. 2019 Feb 1;142(2):312-321
pubmed: 30649233
Ann Neurol. 1997 Apr;41(4):446-52
pubmed: 9124801
J Neurosci. 2010 Mar 10;30(10):3831-8
pubmed: 20220018
PLoS One. 2017 Mar 20;12(3):e0173275
pubmed: 28319124
EMBO Mol Med. 2020 Jul 7;12(7):e11803
pubmed: 32510847
J Huntingtons Dis. 2017;6(4):349-361
pubmed: 29125493
Nat Rev Neurosci. 2017 Oct;18(10):613-626
pubmed: 28855740
Cell. 2019 Aug 22;178(5):1159-1175.e17
pubmed: 31442405
Lab Invest. 2019 Jul;99(7):929-942
pubmed: 30918326
Brain. 2018 Jan 1;141(1):248-270
pubmed: 29206893
J Neurol. 2014 Feb;261(2):291-9
pubmed: 24272589