Potential markers for sample size estimations in hereditary spastic paraplegia type 5

Area of Science:

• Neurology
• Medical Imaging
• Biomarker Discovery

Background:

• Hereditary spastic paraplegias type 5 (SPG5) is a rare neurological disorder.
• Identifying reliable biomarkers is crucial for assessing treatment efficacy in SPG5.

Purpose of the Study:

• To identify potential biomarkers for assessing therapeutic efficacy in SPG5.
• To investigate clinical, cerebrospinal fluid (CSF), and magnetic resonance imaging (MRI) features in SPG5 patients.

Main Methods:

• A cross-sectional study compared 17 SPG5 patients with age- and sex-matched healthy controls.
• Conventional and quantitative MRI of the spinal cord (C1-T9) and brain were performed.
• Clinical status and CSF biomarkers (27-hydroxycholesterol, neurofilament light) were assessed.

Main Results:

• SPG5 patients showed significant spinal cord area reduction, particularly in thoracic levels (41-60%), compared to controls.
• No significant brain signal abnormalities or atrophy were observed in SPG5 patients.
• Spinal cord area measurement at T9 required a smaller sample size (n=22) for clinical trials compared to clinical disability assessment (n=124).

Conclusions:

• SPG5 is characterized by distinct spinal cord atrophy on MRI without significant brain alterations.
• Spinal cord measurements at the T9 level are proposed as a potential endpoint for SPG5 clinical trials.
• This finding can optimize the design and efficiency of future SPG5 therapeutic trials.