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Mov Disord. 2014 Apr;29(4):568-73. doi: 10.1002/mds.25803. Epub 2014 Jan 7.

A randomized, phase 2 clinical trial of lithium carbonate in Machado-Joseph disease.

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Postgraduate Program in Medical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil; Medical Genetics, Hospital de Clínicas de Porto Alegre (HCPA), Porto Alegre, Rio Grande do Sul, Brazil.



Because lithium exerts neuroprotective effects in preclinical models of polyglutamine disorders, our objective was to assess the safety and efficacy of lithium carbonate (0.5-0.8 milliequivalents per liter) in patients with Machado-Joseph disease (spinocerebellar ataxia type 3 [MJD/SCA3]).


For this phase 2, single-center, double-blind, parallel, placebo-controlled trial ( identifier NCT01096082), 62 patients who had MJD/SCA3 with a disease duration ≤10 years and an independent gait were randomly assigned (1:1) to receive either lithium or placebo.


After 24 weeks, 169 adverse events were reported, including 50.3% in the lithium group (P = 1.00; primary safety outcome). Sixty patients (31 in the placebo group and 29 in the lithium group) were analyzed for efficacy (intention-to-treat analysis). Mean progression between groups did not differ according to scores on the Neurological Examination Score for the Assessment of Spinocerebellar Ataxia (NESSCA) after 48 weeks (-0.35; 95% confidence interval, -1.7 to 1.0; primary efficacy outcome). The lithium group exhibited minor progression on the PATA speech-rate (P = 0.002), the nondominant Click Test (P = 0.023), the Spinocerebellar Ataxia Functional Index (P = 0.003), and the Composite Cerebellar Functional Score (P = 0.029).


Lithium was safe and well tolerated, but it had no effect on progression when measured using the NESSCA in patients with MJD/SCA3. This slowdown in secondary outcomes deserves further clarification.


Machado-Joseph disease; clinical trial; lithium; polyglutamine disorders; spinocerebellar ataxias

[Indexed for MEDLINE]

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