D07 Pridopidine maintenance of total functional capacity (tfc) is associated with stabilization of plasma neurofilament light (NFL) levels. (12th September 2022)

• Record Type: Journal Article
• Authors: Geva, Michal; Abdulhayoglu, Deniz Akinc; Gershoni-Emek, Noga; Goldberg, Y Paul; Boulanger, Bruno; Hayden, Michael R
• Is Part Of: Journal of neurology, neurosurgery and psychiatry. Volume 93(2022)Supplement 1
• Page Start: A22
• Page End: A22
• Publication Date: 2022-09-12
• Subjects: pridopidine -- biomarker -- neurofilament light (NfL) -- clinical trial -- functional capacity; Neurology -- Periodicals; Nervous system -- Surgery -- Periodicals; Psychiatry -- Periodicals; 616.8
• DOI: 10.1136/jnnp-2022-ehdn.63
• Languages: English
• ISSNs: 0022-3050

Abstract

Abstract : Background: Pridopidine is a S1R agonist in clinical development for HD and ALS. S1R activation by pridopidine enhances neuroprotective pathways. Increased levels of neurofilament light (NfL) protein indicate neuronal injury, serving as a biomarker that correlates with longitudinal disease progression. In other neurodegenerative diseases (e.g. MS), NfL reduction is associated with clinical efficacy. To date, no treatment has shown stabilization of NfL levels in HD. PRIDE-HD (Ph2) assessed pridopidine for the treatment of HD for 1 year. Post-hoc analysis of early HD patients with available plasma samples (placebo, n=34; pridopidine 45 mg bid, n=31) at baseline and Wk52 examined the effect of pridopidine on NfL levels (Simoa). The association between NfL and TFC (placebo n=41, pridopidine n=37) was modelled by a linear mixed model. Results: There were similar demographics, CAG repeat length, baseline TFC and NfL levels in placebo and pridopidine groups. Pridopidine shows TFC maintenance at 52 weeks ΔTFC +0.09 vs -1.0 in placebo (p=0.0006). Placebo shows the expected annual increase in NfL (ΔNfL+0.05 log2 pg/ml, similar to TRACK-HD (ΔNfL+0.037 log2 pg/ml). However, pridopidine group shows no annual increase in plasma NfL (ΔNfL -0.06 log2 pg/ml).In placebo, increased NfL is associated with decreased TFC (p=0.008). In the pridopidine group, NfL stabilization is associated with TFC maintenance, significantly different from placebo (p=0.02). Significance is maintained after corrections for age (p=0.03), CAG length (p=0.02), BMI (p=0.03) and their combination (p=0.02). Conclusions: Pridopidine 45 mg bid stabilizes plasma NfL levels in association with TFC maintenance in early HD patients.