The therapeutic potential of laquinimod for Huntington’s disease: A systematic review of preclinical and clinical studies

Neuroinflammation is a central contributor to Huntington’s disease (HD) pathogenesis and represents a promising therapeutic target. Laquinimod, an oral immunomodulator with demonstrated neuroprotective effects in preclinical models, has been investigated as a potential treatment for HD. This review critically appraises its preclinical and clinical evidence.
A systematic search (January 2025) was conducted in PubMed, Scopus, Embase, Cochrane Library, and Web of Science using terms including “Huntington’s disease,” “laquinimod,” and “quinoline-3-carboxylic acid.” Preclinical and clinical studies evaluating laquinimod in HD were included. Due to heterogeneity, findings were synthesized qualitatively.
Of 2638 records identified, 10 studies met the inclusion criteria. Preclinical data showed laquinimod improved motor function, reduced neuroinflammation, and promoted myelination, likely via microglial modulation, NF-κB suppression, and increased BDNF expression. Effects on myelin integrity and inflammatory markers were inconsistent. In vitro studies showed limited, variable cytokine modulation in HD patient-derived cells. Clinical trials did not demonstrate significant improvements in motor or functional outcomes, though one study reported minor cognitive and behavioral benefits.
Preclinical evidence suggests laquinimod may modulate motor, inflammatory, and myelination pathways in HD; however, clinical evidence shows no meaningful benefit. Data on long-term safety remain limited. Larger, well-designed trials using standardized biomarkers are needed to clarify its therapeutic potential.
Huntington’s disease (HD) is an inherited brain condition that affects movement, thinking, and mood. Current treatments help with symptoms but cannot stop the disease from getting worse. Laquinimod is a pill that changes how the immune system works and may protect brain cells. Studies in mice with HD showed that laquinimod could improve movement, reduce brain inflammation, and protect nerve cells. Laboratory studies using human cells found that laquinimod could reduce some inflammatory signals, but the effects were weaker and varied. In people with HD, laquinimod was generally safe but did not clearly improve movement, thinking, or daily activities. Some small benefits were seen in a few tests, but they were inconsistent. Overall, laquinimod shows promise in lab and animal studies, but current evidence in humans does not show clear benefits. More research is needed to see if it could help when given at the right dose or early in the disease.