Riluzole in Huntington's disease: a 3‐year, randomized controlled study

Abstract

No neuroprotective or beneficial symptomatic effects of riluzole in Huntington's disease were demonstrated.

Genesis of ER stress in Huntington’s Disease

“…This is consistent with increasing evidence that Htt oligomers and not aggregates are the cytotoxic species in HD [5][6][7] and the reports of UPS inhibition before Htt inclusion into large aggregates [168][169][170]. This might explain why clinical trials of anti-aggregating molecules in HD have been so far unsuccessful [171]. The presence of toxic oligomeric forms (detected with specific antibodies), was found to predict neurodegeneration [172].…”

Treatment of Huntington's Disease

“…Because riluzole retards striatal glutamate release and the pathological consequences in neurotoxic animal models of HD, multiple large trials have been conducted to determine if there is a possible neuroprotective effect. Although there was no clear neuroprotective effect found, riluzole significantly reduced chorea at a dose of 200 mg/day, but not 100 mg/day [97,98]. Benzodiazepines are also frequently used clinically in patients with HD to treat anxiety and chorea, but there is limited evidence to suggest that higher doses of clonazepam (up to 5.5 mg/day) may be needed to suppress chorea [99].…”

Evidence-based guideline: Pharmacologic treatment of chorea in Huntington disease [RETIRED]

“…18 The second RCT (n ϭ 537) found no significant difference in UHDRS chorea scores at 3 years in subjects treated with riluzole 50 mg twice daily (ϩ3.7) or placebo (ϩ3.2) (effect difference 0.5, 95% CI Ϫ0.33 to 1.33). 19 However, 14.4% (26/180) of placebo-treated subjects withdrew to start antichoreic medication vs 9.0% (32/357) of riluzole-treated subjects ( p Ͻ 0.0001). 19 Adverse events.…”