Table 4. Drug trials in patients with mainly dominant ataxias.

Study	Ataxia	Daily dose	Study design	Study period	No. of patients	Outcome
Ristori et al. [69]	Cerebellar ataxias of different etiologies	100 mg riluzole	Randomised, double-blind, placebo-controlled	8 weeks	40	Significant drop in ICARS score (at least 5 points) especially static function, kinetic functions, dysarthria
Zesiewicz et al. [70]	SCA3	1 mg varenicline twice daily	Randomized, double-blind, placebo-controlled, (crossover)	4 weeks titration, 4 weeks 1 mg twice daily	20	Significant improvement of SARA scores for gait, stance, rapid alternating movements, timed walking test, no crossover phase because of drop-outs
Strupp et al. [73]	Cerebellar ataxia of different etiology	5 g/day acetyl-dl-leucine	Open label	1 week	13 (5 SAO A, 1 SCA2, 1 SCA1,2ADCA, 4AOA)	SARA improvement (16.1 vs. 12.8); improvement in SCAFI and EuroQo1-5d-3l
Velazquez-Perez et al. [76]	SCA2	50 mg ZnSO(4) daily or placebo	Randomized, double-blind, placebo-controlled	6 months	36	Significant increase Zn levels in the CSF, non-significant decrease in SARA subscores for gait, posture, stance and rapid alternating movements, reduction of lipid's oxidative damage, reduction of saccadic latency in the zinc-treated group
Assadietal. [157]	FRDA, CA, OPCA	30 mg buspirone HC1 twice daily	Double-blind, placebo controlled, crossover	3 months	20 (10 SCA, 6 CA, 4 FA)	No evidence of an effect of buspirone HC1 on ICARS
Schulte et al. [158]	SCA3	Combination of trimethoprim 160 mg+sulfamethoxazole 800 mg, twice daily for 2 weeks, followed by a combination of trimethoprim 80 mg+sulfamethoxazole, 400 mg, twice daily for 5.5 months	Randomised, double-blind, placebo-controlled, crossove (2 weeks washout)	6 months r	22	No significant improvement in ataxia ranking scale, self-assessment score, static posturography, and results of motor performance testing after 2 weeks and 6 months. No significant effects on the visual system using the achromatic Vision Contrast Test System and the Farnsworth-Munsell 100-hue test for color discrimination
Yabe et al. [74]	SCA6	250 or 500 mg acetazolamide daily	Open-label pilot study	22 months	9	Significant improvement in the ataxia rating scale (ICARS) and body sway analysis by stabilometry until week 48, non-significant effect after 88 weeks
Botez et al. [75]	FRDA, OPCA	200 mg amantadine vs. placebo	Randomized, double-blind, placebo-controlled	3–4 months	30	Efficacy evaluation via visual and auditory reaction time and movement time with right and left hand according to Hamsher and Benton real method. Measurement of homovanillinic acid levels in the CSF

FRDA Friedreich's ataxia, CA cerebellar atrophy, OPCA olivopontocerebellar atrophy, SCA spinocerebellar ataxia (SCA1 spinocerebellar ataxia type 1, SCA2 spinocerebellar ataxia type 2 etc.), CSF cerebrospinal fluid, POLG mutation in the polymerase gamma gene, SAOA sporadic ataxia of unknown origin, ADCA autosomal dominant cerebellar ataxia, AOA ataxia with ocular apraxia, SCAFI SCA functional index (consisting of the PATA test, 8 m walking time, nine-hole PEG test), EQ-VAS visual analog scale of the EQ-5D