Randomized Crossover Trial to Evaluate Chinese Medicine WT for Spinocerebellar Ataxia Type 3 Neuroprotection

Spinocerebellar Ataxia Type 3 (SCA3) is a debilitating autosomal dominant hereditary ataxia, progressively leading to standing imbalance, unsteady gait, dysmetria, fatigue, and depression. Currently, there are no effective treatments or palliative methods available for patients, representing a significant unmet medical need. Previous preclinical research suggests that low-dose growth hormone or its downstream product, insulin-like growth factor I (IGF-1), may slow SCA3 progression in transgenic mice. The main bioactive component of Chinese medicine WT has demonstrated neuroprotective effects against glutamate-induced toxicity, a key pathological mechanism in SCA3, and is known to promote neurogenesis and increase IGF-1 protein expression in ischemic rat brains, providing a rationale for its investigation in SCA3.

This study is designed as a randomized, double-blind, crossover trial to assess the potential neuroprotective effects of Chinese medicine WT in SCA3 patients. Subjects will be recruited from Changhua Christian Hospital, with diagnosis confirmed by gene testing and MRI. Participants will be randomly assigned to receive 3 grams concentrated powder of WT or placebo, twice daily, for 12 weeks. Following a 4-week washout period, participants will crossover to the alternate treatment arm (placebo or WT) for another 12 weeks, concluding with a final 4-week rest period. Five key endpoints will be assessed at multiple checkpoints to evaluate treatment efficacy.

This abstract describes the protocol for a clinical trial, and thus, no results or specific numerical findings are available at this stage. The study aims to evaluate the neuroprotective potential of Chinese medicine WT by measuring a comprehensive set of biomarkers and clinical outcomes. Planned assessments include blood examinations for serum IGF-1, Neurofilament light chain, mitochondria copy number, 8_OHdG, and delta-Ct to gauge disease progression and cellular health. Neurological function will be quantified using the Scale for the Assessment and Rating of Ataxia. Patient-reported outcomes will be captured via the Modified Fatigue Impact Scale and Epworth Sleepiness Scale. Additionally, Handgrip strength test, known to correlate with IGF-1 levels, and serum metabolites will be analyzed. All collected data will be analyzed using Paired-T test or Wilcoxon Ranked Sign Test in SPSS after the trial's completion, with results to be disclosed subsequently. The primary goal is to determine if WT can significantly impact these markers of SCA3 pathology and symptom burden.