We appreciate the letter by Sakai and Miyoshi concerning our ARCHIVES article. They mention substantial deficits in previous studies of T-S in spinocerebellar ataxia (SCA)3/MJD, and they agree that a small number of patients (maximum, 8) and a treatment duration of 4 weeks or less is insufficient to prove therapeutic effects. They underscore the value of quantitative measures in the evaluation of therapeutic effects in ataxia studies.
Presently, a major problem with ataxia trials is the lack of substantial natural history data in almost all subtypes of ataxia. Such data are essential for the statistical calculation of the duration of a trial and the number of patients required to prove or disprove the effectiveness of a drug. A recent study in cooperation with our group1 demonstrated that the assessment of progression in easily determinable and relevant steps, such as (1) onset of gait difficulties, (2) requirement of a walking aid, (3) use of a wheelchair, and (4) death, would take 10 years or more in SCA3/MJD to observe or prevent the progression from one category to the other. More sensitive measures of progression and surrogate markers must be developed, a major challenge for clinical research in the near future. These markers must be evaluated for sensitivity and stability concerning patients' day-to-day fluctuations and interrater variability.
Schulte T, Schöls L. In reply. Arch Neurol. 2002;59(6):1044-1045. doi: