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

Abstract

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.

MR Imaging in Spinocerebellar Ataxias: A Systematic Review

“…Five studies evaluated MR spectroscopy of infratentorial regions in SCA3/MJD [10][11][12][13][14][15][16][17][18][19][20][21][22] ; all of them evaluated cerebellar structures, and only 1 evaluated the brain stem (see On-line Table 1 for the main findings). 19 The N-acetylaspartate/creatine ratio was evaluated in 4 studies with ROIs in the cerebellar hemispheres/cortex, [20][21][22] all with reduced NAA/Cr ratios; 2 of them had inverse correlations with SARA scores.…”

“…4,5 Natural history studies with well-validated SCA scales, such as the Scale for the Assessment and Rating of Ataxia (SARA) 6 and the Neurologic Examination Score for Spinocerebellar Ataxia 7 were concordant with both the very slow disease progression [8][9][10] and the necessity for large sample sizes to test disease-modifying therapies in future randomized clinical trials. [8][9][10][11][12][13] Surrogate biomarkers could hasten randomized clinical trials and drug discoveries for SCA. The number of biomarkers evaluated so far is small, and neuroimaging, particularly MR imaging, is the best-evaluated candidate.…”

Planning future clinical trials in Machado Joseph disease: Lessons from a phase 2 trial

“…Lithium had changed the progression of SCAFI and CCFS after 48 weeks of treatment, with no significant differences on NESSCA and SARA progressions [12]. The relative change to placebo progression [(mean placebo progression − mean lithium progression / mean placebo progression) * 100] with lithium therapy at the study end was 24% for NESSCA and 71% for SARA (indicating less worsening), and 110% for SCAFI and 300% for CCFS (indicating stabilization or improvement).…”

“…A randomized, double-blind, parallel, placebo controlled, single center trial was done in SCA3/MJD patients (disease duration ≤10 years): methods and results were previously reported [12] and are also available in the full protocol link: http://www.hcpa.ufrgs.br/downloads/ Genetica/protocol_lithium_mjd.pdf.…”

“…In a recent randomized, parallel, placebo-controlled 48 week trial we evaluated lithium carbonate safety and efficacy in 62 SCA3/MJD patients [12]. Lithium was considered safe.…”