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Published on: March 11, 2020
A PET-CT study on neuroinflammation in Huntington's disease patients participating in a randomized trial with
Andreas-Antonios Roussakis1, Marta Gennaro1, Mark Forrest Gordon2
1Brain Sciences, Imperial College London, Hammersmith Hospital, London W12 0NN, UK.
Abstract:
Microglia activation, an indicator of central nervous system inflammation, is believed to contribute to the pathology of Huntington's disease. Laquinimod is capable of regulating microglia. By targeting the translocator protein, 11C-PBR28 PET-CT imaging can be used to assess the state of regional gliosis in vivo and explore the effects of laquinimod treatment. This study relates to the LEGATO-HD, multi-centre, double-blinded, Phase 2 clinical trial with laquinimod (US National Registration: NCT02215616). Fifteen patients of the UK LEGATO-HD cohort (mean age: 45.2 ± 7.4 years; disease duration: 5.6 ± 3.0 years) were treated with laquinimod (0.5 mg, N = 4; 1.0 mg, N = 6) or placebo (N = 5) daily. All participants had one 11C-PBR28 PET-CT and one brain MRI scan before laquinimod (or placebo) and at the end of treatment (12 months apart). PET imaging data were quantified to produce 11C-PBR28 distribution volume ratios. These ratios were calculated for the caudate and putamen using the reference Logan plot with the corpus callosum as the reference region. Partial volume effect corrections (Müller-Gartner algorithm) were applied. Differences were sought in Unified Huntington's Disease Rating Scale scores and regional distribution volume ratios between baseline and follow-up and between the two treatment groups (laquinimod versus placebo). No significant change in 11C-PBR28 distribution volume ratios was found post treatment in the caudate and putamen for both those treated with laquinimod (N = 10) and those treated with placebo (N = 5). Over time, the patients treated with laquinimod did not show a significant clinical improvement. Data from the 11C-PBR28 PET-CT study indicate that laquinimod may not have affected regional translocator protein expression and clinical performance over the studied period.
Insights
Laquinimod did not significantly alter translocator protein expression or clinical outcomes in Huntington
Area of Science:
- Neuroscience
- Neuroinflammation
- Neurodegenerative Diseases
Background:
- Microglia activation, a marker of central nervous system inflammation, is implicated in Huntington's disease pathology.
- Laquinimod is a potential modulator of microglia activity.
- Translocator protein (TSPO) expression, assessed via 11C-PBR28 PET-CT imaging, can indicate regional gliosis in vivo.
Purpose of the Study:
- To evaluate the effect of laquinimod on TSPO expression in patients with Huntington's disease using 11C-PBR28 PET-CT imaging.
- To assess the impact of laquinimod on clinical outcomes in Huntington's disease patients.
- To explore the relationship between neuroinflammation markers and clinical status during laquinimod treatment.
Main Methods:
- A multi-center, double-blinded, Phase 2 clinical trial (LEGATO-HD) involving 15 Huntington's disease patients.
- Patients received daily laquinimod (0.5mg or 1.0mg) or placebo for 12 months.
- 11C-PBR28 PET-CT and MRI scans were performed at baseline and follow-up; PET data were quantified for distribution volume ratios in the caudate and putamen, with partial volume correction.
Main Results:
- No significant changes in 11C-PBR28 distribution volume ratios were observed in the caudate or putamen after laquinimod or placebo treatment.
- Patients treated with laquinimod did not demonstrate significant clinical improvement on Unified Huntington's Disease Rating Scale scores over the study period.
- Laquinimod treatment did not appear to affect regional TSPO expression or clinical performance in this cohort.
Conclusions:
- Laquinimod treatment did not modulate in vivo TSPO expression in the brains of Huntington's disease patients over 12 months.
- The study suggests laquinimod may not be effective in altering neuroinflammation or improving clinical symptoms in Huntington's disease.
- Further research is needed to explore potential therapeutic strategies targeting neuroinflammation in Huntington's disease.
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