Outcome Measures and Biomarkers for Clinical Trials in Hereditary Spastic Paraplegia: A Scoping Review

Sue-Faye Siow; Dennis Yeow; Laura I Rudaks; Fangzhi Jia; Gautam Wali; Carolyn M Sue; Kishore R Kumar

doi:10.3390/genes14091756

Outcome Measures and Biomarkers for Clinical Trials in Hereditary Spastic Paraplegia: A Scoping Review

Genes (Basel). 2023 Sep 3;14(9):1756. doi: 10.3390/genes14091756.

Authors

Sue-Faye Siow^{1

2}, Dennis Yeow^{1

3

4

5

6}, Laura I Rudaks^{1

2

4

5}, Fangzhi Jia¹, Gautam Wali^{1

3}, Carolyn M Sue^{1

3

6

7}, Kishore R Kumar^{1

4

5

7}

Affiliations

¹ Sydney Medical School, University of Sydney, Camperdown 2050, Australia.
² Department of Clinical Genetics, Royal North Shore Hospital, St Leonards 2065, Australia.
³ Neuroscience Research Australia, University of New South Wales, Randwick 2031, Australia.
⁴ Rare Disease Program, Garvan Institute of Medical Research, Darlinghurst 2010, Australia.
⁵ Translational Neurogenomics Group, Molecular Medicine Laboratory and Department of Neurology, Concord Hospital, Concord 2139, Australia.
⁶ Neurodegenerative Service, Prince of Wales Hospital, Randwick 2031, Australia.
⁷ School of Clinical Medicine, UNSW Medicine & Health, University of New South Wales, Kensington 2052, Australia.

Abstract

Hereditary spastic paraplegia (HSP) is characterized by progressive lower limb spasticity. There is no disease-modifying treatment currently available. Therefore, standardized, validated outcome measures to facilitate clinical trials are urgently needed. We performed a scoping review of outcome measures and biomarkers for HSP to provide recommendations for future studies and identify areas for further research. We searched Embase, Medline, Scopus, Web of Science, and the Central Cochrane database. Seventy studies met the inclusion criteria, and eighty-three outcome measures were identified. The Spastic Paraplegia Rating Scale (SPRS) was the most widely used (27 studies), followed by the modified Ashworth Scale (18 studies) and magnetic resonance imaging (17 studies). Patient-reported outcome measures (PROMs) were infrequently used to assess treatment outcomes (28% of interventional studies). Diffusion tensor imaging, gait analysis and neurofilament light chain levels were the most promising biomarkers in terms of being able to differentiate patients from controls and correlate with clinical disease severity. Overall, we found variability and inconsistencies in use of outcome measures with a paucity of longitudinal data. We highlight the need for (1) a standardized set of core outcome measures, (2) validation of existing biomarkers, and (3) inclusion of PROMs in HSP clinical trials.

Keywords: biomarkers; clinical trials; hereditary spastic paraplegia; outcome measures; scoping review.

Publication types

Review
Research Support, Non-U.S. Gov't

MeSH terms

Biomarkers
Diffusion Tensor Imaging
Humans
Outcome Assessment, Health Care
Paraplegia
Spastic Paraplegia, Hereditary* / diagnosis
Spastic Paraplegia, Hereditary* / genetics
Spastic Paraplegia, Hereditary* / therapy

Substances

Biomarkers

Grants and funding

S.-F.S. is the recipient of the National Health and Medical Research Council and Australian and New Zealand Association of Neurologists Postgraduate Scholarships APP113610.