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046 A critical review of biomarkers for hereditary spastic paraplegia
  1. Sue-Faye Siow1,2,3,
  2. Gautam Wali1,2,
  3. Carolyn Sue4,1,2,
  4. Kishore R Kumar4,1,2,5
  1. 1Northern Clinical School, University of Sydney, Sydney, NSW, Australia
  2. 2Neurogenetics, Kolling Institute, Sydney, NSW, Australia
  3. 3Clinical Genetics, Royal North Shore Hospital, Sydney, NSW, Australia
  4. 4Neurology, Royal North Shore Hospital, Artarmon, NSW, Australia
  5. 5Garvan Institute of Medical Research, Sydney, NSW, Australia


Introduction Hereditary spastic paraplegia (HSP) is a rare neurodegenerative condition characterised by lower limb weakness and spasticity. Currently, treatment is symptomatic and there is no disease modifying therapy. Though candidate therapeutic agents have been identified, sensitive biomarkers to measure treatment efficacy in clinical drug trials are lacking. There are many challenges in the search for appropriate biomarkers including the rarity of HSP, clinical and genetic heterogeneity of HSP and slow disease progression.

Methods We performed a search on PubMed and Medline using the search terms (‘hereditary spastic paraplegia’ OR ‘spastic paraparesis’) AND ‘biomarker*’. We searched the reference lists of relevant articles to identify further studies. We collected data on number of participants, HSP genotype, methodology, and outcomes.

Results 72 papers were identified: 2 on Rating scales, 9 on gait analysis, 33 on neurophysiological measures, 23 on neuroimaging markers and 5 on biochemical markers. The studies reviewed demonstrated variation in methodologies and outcomes, including mixed genotype (41/72 papers) and genotype-specific (31/72 papers) patient cohorts, varied neurophysiological techniques and different outcome measures. 68/72 studies reviewed had small patient numbers (<50 patients). All potential biomarkers reviewed were able to differentiate HSP patients from controls. Only diffusion tensor imaging (DTI) parameters showed significant correlation with disease severity.

Conclusion Although useful as diagnostic biomarkers, further studies are required to evaluate these potential biomarkers longitudinally and to assess their reliability as surrogates for underlying neurodegenerative changes and clinical disease severity. DTI showed the most promise as a biomarker for disease severity in HSP.

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