studio sperimentale lirh malattia di huntington


what is legato-Hd

Legato-HD is a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial to evaluate the efficacy and safety of treatment with laquinimod in patients with Huntington's disease.

how the experimental molecule works (laquinimod)

Laquinimod is a small molecule that passively crosses the blood-brain barrier and is detectable in the tissues of the central nervous system (CNS). It has also been tested for the treatment of Multiple Sclerosis (MS). Several studies have shown that laquinimod exhibits both anti-inflammatory and neuroprotective effects by modulating important central and peripheral pathogenic pathways implicated in various neurodegenerative diseases, including Huntington's disease. The exact mechanism by which laquinimod exerts its neuroprotective effects is not fully understood, but laquinimod has been proposed to reduce leukocyte migration into the central nervous system.

Where did the study take place

The study involved 48 sites in 10 countries (United States, Canada, Czech Republic, Germany, Italy, the Netherlands, Portugal, Russia, Spain and the United Kingdom).
Number of participants: 352

Method of Administration

Method of administration: oral.
3 different dosages: 0.5 mg - 1 mg - 1.5 mg.
Since 10 January 2016, following the recommendation of the Data Safety Monitoring Board, treatment with a dose of 1.5 mg of laquinimod has been suspended as a safety measure.

Inclusion criteria

Symptomatic patients with early disease participated in the study.
The specific criteria were:
- aged between 21 and 55;
- Number of CAG triplets between 36 and 49;
- Total Motor Score (TMS) score> 5;
- Total Functional Capacity (TFC) score ≥ 8;

Duration (year start-year end)

Started in October 2014, ended in June 2018.

Why did not we go to phase 3

The main objective of the trial was to evaluate the efficacy of laquinimod after 52 weeks of therapy, intended as a reduction in motor symptoms presented by patients with Huntington. Unfortunately, this goal was not achieved because the group of patients taking the drug showed no significant differences compared to that taking the placebo. For this reason, the trail did not go through phase 3 of testing.
The secondary objective was, however, to evaluate the reduction of brain atrophy after 52 weeks of treatment. Patients taking the drug showed a reduction in atrophy in some brain regions (caudate, white matter and overall brain atrophy) compared to the group of patients taking the placebo. This result, however, was unfortunately not considered sufficient to allow moving on to a subsequent experimentation phase.

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