Table 2.

Therapeutic interventions for treatment of spinocerebellar ataxias and notable clinical trials.

Name	Notable Clinical Trials	SCA Types	Intervention	Outcome
SYMPTOMATIC INTERVENTION
Pharmacologics
Riluzole	Ristori et al [15]	1, 2, 28	100 mg daily	The proportion of patients who experienced a 5-point decrease in ICARS score was significantly higher in patients taking riluzole compared to the placebo group after four weeks (9/19 vs. 1/19; odds ratio [OR] 16.2; 95% confidence interval [CI] 1.8–147.1) and eight weeks (13/19 vs. 1/19; OR 39.0; 95% CI 4.2–364.2)[16]. There was also a significant mean change in the total ICARS in the riluzole group compared to placebo (7.05 [4.96] vs. 0.16 [2.65] (p < 0.001))
	Romani et al [16]	NR(38 subjects with SCA)	50 mg twice daily	The study found that 50% (14/28) of patients in the riluzole group had a one point decrease in SARA score compared to 11% (3/27) of patients in the placebo group (OR 8.00, 95% CI 1.95–32.83; p = 0.002)
Thyrotropin Releasing Hormone	Sobue et al [35]	NR(254 patients with SCD)	2 mg or .5 mg daily	Overall, patients randomized to receive TRH 2 mg had better standing, gait, speech, and writing when compared to the placebo group. However, about 50% of patients taking 2 mg TRH had adverse effects, including headache and nausea
Rotaviterelin	Nishizawa et al (2 trials) [36]	6, 31	1.6 mg or 2.4 mg daily	in the pooled analysis of data from the two studies, patients presented a more significant reduction in SARA total score when taking rovatirelin compared with placebo (1.64 vs. 1.03; 95% CI- 1.16 to 0.06; p = 0.029)
Varenicline	Zesiewicz et al [41]	3	1 mg twice daily	Patients taking varenicline experienced improvements in the SARA subsections for gait (p = 0.04), stance (p = 0.03), rapid alternating movements (p = 0.003), timed 25-foot walk (p = 0.05) and Beck Depression Inventory scores (p = 0.03) compared to patients taking placebo
Buspirone	Assadi et al [47]	1,2,3,6,17	30 mg twice daily	Buspirone was not found to be superior to placebo: ICARS scores (baseline = 42.63 ± 18.89; placebo = 46 ± 18.98 buspirone = 44.26 ± 19.64, p =0.24)
Valproic Acid	Lei et al [48]	3	800 mg or 1200 mg daily	The mean change in the total SARA total score was significantly greater in the 1200-mg/d group(−2.05) versus the 800-mg/d (−1.58) and the placebo (−0.75) groups (analysis of variance p = 0.021)
Lithium	Saute et al [52]	3	300 mg daily	While lithium was determined to be safe and tolerable, it had no statistically significant effect on overall NESSCA scores (p =0.222). The lithium treatment group presented statistically significant progression in secondary outcome assessments, including the nondominant Click Test (p =0.023), the PATA rate test (p =0.002), the SCAFI (p=0.003), and the CCFS (p =0.029)
	Sacca et al [53]	2	150 mg twice daily(up to 1500 mg)	Lithium was found to be safe but did not demonstrate significant differences in SARA scores. BDI-II score significantly decreased in lithium group (p < 0.05).
Amantadine	Botez et al [55]	None (FRDA and MSA-C	200 mg daily	Significant improvement was noted in MSA-C but not in FRDA
Acetazolamide	Yabe et al [62]	6	500 mg daily	Cerebral ataxia was shown to be reduced with acetazolamide treatment, as evidenced by a statistically significant decrease in total ataxia rating scores, and posture and kinetics subscores (p < 0.05)
Trehalose	Noorsaykin et al [66]	3	100 mg daily	Results demonstrated statistically significant improvements in SARA scores (p = 0.05) and 8-minute walking test scores(p = 0.007)
Non-Pharmacologic Rehabilitative Therapy	Miyai et al [67]	6,31	PT and OT, 2 hours on weekdays and 1 hour on weekends	The immediate treatment group demonstrated significantly greater improvements in SARA score in the short-term, especially in truncal ataxia, compared with the delayed-entry treatment group over the 4 weeks (p < 0.001). In addition, at the 24-week follow-up, more than 50% of all individuals maintained these improvements.
	Bastian et al [68]	3,5,6,8,17	Home balance exercises	Neurological and functional assessments done 5 times over the course of the exercise program revealed significant improvements in walking speed, dynamic gait index, stride length, and percent double limb support time (p < 0.05). However, no change was seen in ICARS scores or ABC scores
Non-Invasive Neurostimulation	Shiga et al [73]	1,3,6	rTMS	In comparing the active TMS and sham groups, improvement of the TMS group was found to be statistically significant for the timed 10-meter walk, 10-meter step assessment, and standing capacity (p < 0.05). Among the active-TMS group, blood flow to the pons and cerebellum was significantly increased (p < 0.005) but no significant increase was noted in the cerebral cortices.
	Manor et al [74]	1,2,3,6,8,13	rTMS	Subjects receiving rTMS demonstrated a significant improvement in the SARA sub-score for “stance” (p = 0.002) from baseline to 1-month follow-up when compared to the sham group. No significant changes were observed in the 9-hole peg test or TUG assessment
	Franca et al [75]	3	rTMS	The rTMS group was shown to have statistically significant improvement in SARA scores (median 10.2 for rTMS vs. median 12.8 for sham (p = 0.002)). Improvements in ICARS scores were also noted to be significant between rTMS and sham groups (median 29.0 for rTMS and 32.8 for sham (p = 0.005)
	Benussi et al 2015 [78]	1,2,38	tDCS	In comparing the sham and tDCS group, tDCS subjects demonstrated a statistically significant improvement in scores measured pre and post stimulation for all assessments (p < 0.001 for SARA, ICARS, and 8-meter walk; p = 0.012 for 9-hole-peg test)
	Benussi et al 2018 [79]	6,14,38	tDCS	Statistically significant improvements in functional performance assessments of SARA and ICARS(p < 0.001)
BCAAs	Mori et al [85]	6,7	1.5,3.0, or 6.0 mg	When comparing placebo and treatment groups, the ICARS scores significantly improved (p < 0.01) from pre- to post-treatment