{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T22:22:13Z","timestamp":1788387733342,"version":"build-2803163510"},"reference-count":66,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T00:00:00Z","timestamp":1545350400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000065","name":"National Institute of Neurological Disorders and Stroke","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000065","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"DOI":"10.3389\/fneur.2018.01017","type":"journal-article","created":{"date-parts":[[2018,12,21]],"date-time":"2018-12-21T15:05:35Z","timestamp":1545404735000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":19,"title":["Clinical Trial Designs and Measures in Hereditary Spastic Paraplegias"],"prefix":"10.3389","volume":"9","author":[{"given":"Brian","family":"Trummer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dietrich","family":"Haubenberger","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Craig","family":"Blackstone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2018,12,21]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1159\/000358801","article-title":"The global epidemiology of hereditary ataxia and spastic paraplegia: a systematic review of prevalence studies","volume":"42","author":"Ruano","year":"2014","journal-title":"Neuroepidemiology"},{"key":"B2","doi-asserted-by":"publisher","first-page":"871","DOI":"10.1136\/jnnp.44.10.871","article-title":"Hereditary \u201cpure\u201d spastic paraplegia: a clinical and genetic study of 22 families","volume":"44","author":"Harding","year":"1981","journal-title":"J Neurol Neurosurg Psychiatry"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1088","DOI":"10.1093\/hmg\/ddv632","article-title":"Conserved pharmacological rescue of hereditary spastic paraplegia-related phenotypes across model organisms","volume":"25","author":"Julien","year":"2016","journal-title":"Hum Mol Genet"},{"key":"B4","doi-asserted-by":"publisher","first-page":"2517","DOI":"10.1093\/hmg\/ddy156","article-title":"Impaired mitochondrial dynamics underlie axonal defects in hereditary spastic paraplegias","volume":"27","author":"Denton","year":"2018","journal-title":"Hum Mol Genet"},{"key":"B5","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1186\/s13024-015-0064-1","article-title":"Tau missorting and spastin-induced microtubule disruption in neurodegeneration: Alzheimer disease and hereditary spastic paraplegia","volume":"10","author":"Zempel","year":"2015","journal-title":"Mol Neurodegener"},{"key":"B6","doi-asserted-by":"publisher","first-page":"494","DOI":"10.1242\/bio.20147641","article-title":"Low dose tubulin-binding drugs rescue peroxisome trafficking deficit in patient-derived stem cells in Hereditary Spastic Paraplegia","volume":"3","author":"Fan","year":"2014","journal-title":"Biol Open"},{"key":"B7","doi-asserted-by":"publisher","first-page":"435","DOI":"10.3389\/fncel.2015.00435","article-title":"Automated measurement of fast mitochondrial transport in neurons","volume":"9","author":"Miller","year":"2015","journal-title":"Front Cell Neurosci"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1005","DOI":"10.1242\/dmm.013987","article-title":"Cold temperature improves mobility and survival in Drosophila models of autosomal-dominant hereditary spastic paraplegia (AD-HSP)","volume":"7","author":"Baxter","year":"2014","journal-title":"Dis Models Mech"},{"key":"B9","doi-asserted-by":"publisher","first-page":"2527","DOI":"10.1093\/hmg\/ddt644","article-title":"Gene dosage-dependent rescue of HSP neurite defects in SPG4 patients' neurons","volume":"23","author":"Havlicek","year":"2014","journal-title":"Hum. Mol. Genet"},{"key":"B10","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1172\/JCI26210","article-title":"Intramuscular viral delivery of paraplegin rescues peripheral axonopathy in a model of hereditary spastic paraplegia","volume":"116","author":"Pirozzi","year":"2006","journal-title":"J Clin Invest"},{"key":"B11","doi-asserted-by":"publisher","first-page":"e36505","DOI":"10.1371\/journal.pone.0036505","article-title":"Transcriptional and post-transcriptional regulation of SPAST, the gene most frequently mutated in hereditary spastic paraplegia","volume":"7","author":"Henson","year":"2012","journal-title":"PLoS ONE"},{"key":"B12","doi-asserted-by":"publisher","first-page":"317","DOI":"10.1093\/brain\/awv371","article-title":"Congenital disorders of autophagy: an emerging novel class of inborn errors of neuro-metabolism","volume":"139","author":"Ebrahimi-Fakhari","year":"2016","journal-title":"Brain"},{"key":"B13","doi-asserted-by":"publisher","first-page":"3112","DOI":"10.1093\/brain\/awx273","article-title":"Hereditary spastic paraplegia type 5: natural history, biomarkers and a randomized controlled trial","volume":"140","author":"Sch\u00f6ls","year":"2017","journal-title":"Brain"},{"key":"B14","doi-asserted-by":"publisher","first-page":"72","DOI":"10.1093\/brain\/awx297","article-title":"Plasma oxysterols: biomarkers for diagnosis and treatment in spastic paraplegia type 5","volume":"141","author":"Marelli","year":"2018","journal-title":"Brain"},{"key":"B15","doi-asserted-by":"publisher","first-page":"2783","DOI":"10.1007\/s00415-015-7971-5","article-title":"Treatment of SPG5 with cholesterol-lowering drugs","volume":"262","author":"Mignarri","year":"2015","journal-title":"J Neurol"},{"key":"B16","doi-asserted-by":"publisher","first-page":"799","DOI":"10.1242\/dmm.015719","article-title":"Fishing for causes and cures of motor neuron disorders","volume":"7","author":"Patten","year":"2014","journal-title":"Dis Model Mech"},{"key":"B17","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1172\/JCI200420138","article-title":"Axonal degeneration in paraplegin-deficient mice is associated with abnormal mitochondria and impairment of axonal transport","volume":"113","author":"Ferreirinha","year":"2004","journal-title":"J Clin Invest"},{"key":"B18","doi-asserted-by":"publisher","first-page":"3604","DOI":"10.1093\/hmg\/dds191","article-title":"Spg20 \u2212\/\u2212 mice reveal multimodal functions for Troyer syndrome protein spartin in lipid droplet maintenance, cytokinesis and BMP signaling","volume":"21","author":"Renvois\u00e9","year":"2012","journal-title":"Hum Mol Genet"},{"key":"B19","doi-asserted-by":"publisher","first-page":"4273","DOI":"10.1172\/JCI65665","article-title":"A spastic paraplegia mouse model reveals REEP1-dependent ER shaping","volume":"123","author":"Beetz","year":"2013","journal-title":"J Clin Invest"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1003988","article-title":"A hereditary spastic paraplegia mouse model supports a role of ZFYVE26\/SPASTIZIN for the endolysosomal system","author":"Khundadze","year":"2013","journal-title":"PLoS Genet"},{"key":"B21","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1007\/s10048-010-0252-7","article-title":"Targeted disruption of the Mast syndrome gene SPG21 in mice impairs hind limb function and alters axon branching in cultured cortical neurons","volume":"11","author":"Soderblom","year":"2010","journal-title":"Neurogenetics"},{"key":"B22","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1152\/japplphysiol.00991.2004","article-title":"Inter- and intrastrain variation in mouse critical running speed","volume":"98","author":"Billat","year":"2005","journal-title":"J Appl Physiol"},{"key":"B23","doi-asserted-by":"publisher","first-page":"3544","DOI":"10.1093\/hmg\/ddl431","article-title":"A mutation of spastin is responsible for swellings and impairment of transport in a region of axon characterized by changes in microtubule composition","volume":"15","author":"Tarrade","year":"2006","journal-title":"Hum Mol Genet"},{"key":"B24","doi-asserted-by":"publisher","first-page":"430","DOI":"10.1212\/01.wnl.0000228242.53336.90","article-title":"The Spastic Paraplegia Rating Scale (SPRS): a reliable and valid measure of disease severity","volume":"67","author":"Sch\u00fcle","year":"2006","journal-title":"Neurology"},{"key":"B25","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1590\/S0037-86822012000300006","article-title":"Comparison between the spastic paraplegia rating scale, Kurtzke scale, and Osame scale in the tropical spastic paraparesis\/myelopathy associated with HTLV","volume":"45","author":"Adry","year":"2012","journal-title":"Rev Soc Bras Med Trop"},{"key":"B26","doi-asserted-by":"publisher","first-page":"147","DOI":"10.2340\/16501977-1909","article-title":"Functional effects of botulinum toxin type-A treatment and subsequent stretching of spastic calf muscles: a study in patients with hereditary spastic paraplegia","volume":"47","author":"de","year":"2015","journal-title":"J Rehabil Med"},{"key":"B27","doi-asserted-by":"publisher","first-page":"158","DOI":"10.1186\/1750-1172-8-158","article-title":"Electrophysiological characterisation of motor and sensory tracts in patients with hereditary spastic paraplegia (HSP)","volume":"8","author":"Karle","year":"2013","journal-title":"Orphanet J Rare Dis"},{"key":"B28","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1053\/apmr.2001.9396","article-title":"Validity and reliability comparison of 4 mobility measures in patients presenting with neurologic impairment","volume":"82","author":"Rossier","year":"2001","journal-title":"Arch Phys Med Rahabil"},{"key":"B29","doi-asserted-by":"publisher","first-page":"6","DOI":"10.3109\/03790799009166594","article-title":"Mobility after stroke: reliability of measures of impairment and disability","volume":"12","author":"Collen","year":"1990","journal-title":"Int Disabil Stud"},{"key":"B30","doi-asserted-by":"publisher","first-page":"206","DOI":"10.1093\/ptj\/67.2.206","article-title":"Interrater reliability of a modified Ashworth scale of muscle spasticity","volume":"67","author":"Bohannon","year":"1987","journal-title":"Phys Ther"},{"key":"B31","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1097\/01241398-200001000-00017","article-title":"Reliability and validity of the Gillette Functional Assessment Questionnaire as an outcome measure in children with walking disabilities","volume":"20","author":"Novacheck","year":"2000","journal-title":"J Pediatr Orthop"},{"key":"B32","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1016\/j.clineuro.2014.05.024","article-title":"Intrathecal baclofen therapy for the symptomatic treatment of hereditary spastic paraplegia","volume":"123","author":"Margetis","year":"2014","journal-title":"Clin Neurol Neurosurg"},{"key":"B33","doi-asserted-by":"crossref","first-page":"13","DOI":"10.2340\/1650197771331","article-title":"The post-stroke hemiplegic patient","volume":"7","author":"Fugl-Meyer","year":"1975","journal-title":"Scand J Rehabil Med"},{"key":"B34","doi-asserted-by":"publisher","first-page":"142","DOI":"10.1111\/j.1532-5415.1991.tb01616.x","article-title":"The timed \u201cUp & Go\u201d: a test of basic functional mobility for frail elderly persons","volume":"39","author":"Podsiadlo","year":"1991","journal-title":"J Am Geriatr Soc"},{"key":"B35","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1177\/135245859700300104","article-title":"The MS impairment scale: a pragmatic approach to the assessment of impairment in patients with multiple sclerosis","volume":"3","author":"Ravnborg","year":"1997","journal-title":"Mult Scler"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1577","DOI":"10.1093\/brain\/awp056","article-title":"Prevalence of hereditary ataxia and spastic paraplegia in southeast Norway: a population-based study","volume":"132","author":"Erichsen","year":"2009","journal-title":"Brain"},{"key":"B37","doi-asserted-by":"publisher","first-page":"14","DOI":"10.1016\/j.clineuro.2014.02.002","article-title":"Hereditary spastic paraparesis in adults: a clinical and genetic perspective from Tuscany","volume":"120","author":"Orsucci","year":"2014","journal-title":"Clin Neurol Neurosurg"},{"key":"B38","doi-asserted-by":"publisher","first-page":"1078","DOI":"10.1093\/brain\/awn026","article-title":"REEP1 mutation spectrum and genotype\/phenotype correlation in hereditary spastic paraplegia type 31","volume":"131","author":"Beetz","year":"2008","journal-title":"Brain"},{"key":"B39","doi-asserted-by":"publisher","first-page":"106","DOI":"10.3389\/fnmol.2018.00106","article-title":"Differential expression of several miRNAs and the host genes AATK and DNM2 in leukocytes of sporadic ALS patients","volume":"11","author":"Vrabec","year":"2018","journal-title":"Front Mol Neurosci"},{"key":"B40","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1089\/mab.2013.0015","article-title":"A monoclonal antibody against human MUDENG protein","volume":"32","author":"Wagley","year":"2013","journal-title":"Monoclon Antib Immunodiagn Immunother"},{"key":"B41","doi-asserted-by":"publisher","first-page":"398","DOI":"10.1111\/j.1468-1331.2012.03803.x","article-title":"Novel SPG10 mutation associated with dysautonomia, spinal cord atrophy, and skin biopsy abnormality","volume":"20","author":"Collongues","year":"2013","journal-title":"Eur J Neurol"},{"key":"B42","doi-asserted-by":"publisher","first-page":"1252","DOI":"10.1007\/s00415-009-5109-3","article-title":"Two novel CYP7B1 mutations in Italian families with SPG5: a clinical and genetic study","volume":"256","author":"Criscuolo","year":"2009","journal-title":"J Neurol"},{"key":"B43","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1212\/01.wnl.0000319646.23052.d1","article-title":"SPG11 compound mutations in spastic paraparesis with thin corpus callosum","volume":"71","author":"Samaranch","year":"2008","journal-title":"Neurology"},{"key":"B44","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.jns.2008.10.030","article-title":"Proton magnetic resonance spectroscopy and cognition in patients with spastin mutations","volume":"277","author":"Erichsen","year":"2009","journal-title":"J Neurol Sci"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1073","DOI":"10.1016\/j.ajhg.2012.10.017","article-title":"Mutations in DDHD2, encoding an intracellular phospholipase A1, cause a recessive form of complex hereditary spastic paraplegia","volume":"91","author":"Schuurs-Hoeijmakers","year":"2012","journal-title":"Am J Hum Genet"},{"key":"B46","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1038\/nrneurol.2014.79","article-title":"Ophthalmic manifestations of inherited neurodegenerative disorders","volume":"10","author":"Kersten","year":"2014","journal-title":"Nat Rev Neurol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"2980","DOI":"10.1093\/brain\/aws240","article-title":"Spastic paraplegia gene 7 in patients with spasticity and\/or optic neuropathy","volume":"135","author":"Klebe","year":"2012","journal-title":"Brain"},{"key":"B48","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1016\/j.brainresbull.2007.06.018","article-title":"Motor and somatosensory evoked potentials in Autosomal Dominant Hereditary Spastic Paraparesis (ADHSP) linked to chromosome 2p, SPG4","volume":"74","author":"Sartucci","year":"2007","journal-title":"Brain Res Bull"},{"key":"B49","first-page":"794","article-title":"Intrathecal baclofen in hereditary spastic paraparesis","volume":"73","author":"Meythaler","year":"1992","journal-title":"Arch Phys Med Rehabil"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1285","DOI":"10.1007\/s00415-015-7707-6","article-title":"Dalfampridine in hereditary spastic paraplegia: a prospective, open study","volume":"262","author":"Bereau","year":"2015","journal-title":"J Neurol."},{"key":"B51","doi-asserted-by":"publisher","first-page":"961","DOI":"10.1001\/archneur.58.6.961","article-title":"Use of the multiple sclerosis functional composite as an outcome measure in a phase 3 clinical trial","volume":"58","author":"Cohen","year":"2001","journal-title":"Arch Neurol"},{"key":"B52","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1212\/WNL.60.1.31","article-title":"Measuring the impact of MS on walking ability: the 12-Item MS Walking Scale (MSWS-12)","volume":"60","author":"Hobart","year":"2003","journal-title":"Neurology"},{"key":"B53","doi-asserted-by":"publisher","first-page":"663","DOI":"10.1111\/j.1468-1331.2007.01812.x","article-title":"Double-blind crossover trial of gabapentin in SPG4-linked hereditary spastic paraplegia","volume":"14","author":"Scheuer","year":"2007","journal-title":"Eur J Neurol"},{"key":"B54","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1097\/00002826-199110000-00003","article-title":"L-threonine in the treatment of spasticity","volume":"14","author":"Growdon","year":"1991","journal-title":"Clin Neuropharmacol"},{"key":"B55","doi-asserted-by":"publisher","first-page":"1468","DOI":"10.1002\/mds.20973","article-title":"Methylphenidate fails to improve gait and muscle tone in patients with sporadic and hereditary spastic paraplegia","volume":"21","author":"Klebe","year":"2006","journal-title":"Mov Disord"},{"key":"B56","doi-asserted-by":"publisher","first-page":"2414","DOI":"10.1007\/s00415-013-7044-6","article-title":"Exome sequencing expands the mutational spectrum of SPG8 in a family with spasticity responsive to L-DOPA treatment","volume":"260","author":"Bettencourt","year":"2013","journal-title":"J Neurol"},{"key":"B57","doi-asserted-by":"publisher","first-page":"553","DOI":"10.1002\/mds.23552","article-title":"Novel mutations in SPG11 cause hereditary spastic paraplegia associated with early-onset levodopa-responsive Parkinsonism","volume":"26","author":"Guidubaldi","year":"2011","journal-title":"Mov Disord"},{"key":"B58","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1523\/JNEUROSCI.2948-13.2014","article-title":"StartReact restores reaction time in HSP: evidence for subcortical release of a motor program","volume":"34","author":"Nonnekes","year":"2014","journal-title":"J Neurosci"},{"key":"B59","doi-asserted-by":"publisher","first-page":"1074","DOI":"10.1016\/j.gaitpost.2014.01.010","article-title":"The effect of hydrotherapy treatment on gait characteristics of hereditary spastic paraparesis patients","volume":"39","author":"Zhang","year":"2014","journal-title":"Gait Posture"},{"key":"B60","doi-asserted-by":"publisher","first-page":"93","DOI":"10.3233\/NRE-141196","article-title":"Robotic gait training improves motor skills and quality of life in hereditary spastic paraplegia","volume":"36","author":"Bertolucci","year":"2015","journal-title":"NeuroRehabilitation"},{"key":"B61","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1007\/s10545-014-9695-6","article-title":"Liver disease in infancy caused by oxysterol 7 \u03b1-hydroxylase deficiency: successful treatment with chenodeoxycholic acid","volume":"37","author":"Dai","year":"2014","journal-title":"J Inherit Metab Dis"},{"key":"B62","volume-title":"2049","year":"1983"},{"key":"B63","volume-title":"Rare Diseases: Common Issues in Drug Development Guidance for Industry Draft Guidance","year":"2015"},{"key":"B64","volume-title":"Guidance for Industry and FDA Staff Qualification Process for Drug Development Tools","year":"2014"},{"key":"B65","volume-title":"Guidance for Industry E16 Biomarkers Related to Drug or Biotechnology Product Development: Context, Structure, and Format of Qualification Submissions","year":"2011"},{"key":"B66","first-page":"157","article-title":"Recovery patterns of motor and somatosensory evoked potentials following treatment of vitamin B12 deficiency","volume":"95","author":"Wu","year":"1996","journal-title":"J Formos Med Assoc"}],"container-title":["Frontiers in Neurology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fneur.2018.01017\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T11:10:35Z","timestamp":1694517035000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/article\/10.3389\/fneur.2018.01017\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,12,21]]},"references-count":66,"alternative-id":["10.3389\/fneur.2018.01017"],"URL":"https:\/\/doi.org\/10.3389\/fneur.2018.01017","relation":{},"ISSN":["1664-2295"],"issn-type":[{"value":"1664-2295","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,12,21]]},"article-number":"1017"}}