Abstract
Purpose :
Superactivated platelets (SAPs) are a procoagulant subtype of activated platelets that play a significant role in thrombotic processes. Previous studies have found that SAPs are increased in degenerative diseases including Alzheimer’s disease and primary-open angle glaucoma (POAG). In this study, SAPs were measured in participants with intermediate and advanced dry AMD. In addition, SAPs were evaluated longitudinally before and after at least 1 year of participation in a phase 1/2 clinical trial (NCT05062486) in which participants took either curcumin or a combination of resveratrol, quercetin, and curcumin (RQC).
Methods :
AMD participants (n=22) were enrolled in a 2-year phase 2 clinical trial at Zaparackas and Knepper, Ltd. in Chicago, IL. Baseline SAPs were compared between AMD and age-matched normal control participants previously evaluated. SAPs were also evaluated longitudinally at baseline, 6, 12, and 24 months in a subset of participants (RQC n=6, curcumin n=6). Flow cytometry was used to identify SAPs, which were defined as CD41-positive and PAC1-negative platelets that exhibit surface fibrinogen binding detected using biotinylated fibrinogen. A responder analysis was conducted with responders defined as participants with at least a 15% decrease in SAP % from baseline.
Results :
Baseline SAPs were significantly increased in AMD (44.6 ± 5.7%) compared with controls (34.3 ± 6.9%, p<0.0001). After 12 months of oral treatment, SAPs were significantly decreased from baseline in participants taking RQC (-12.4%, p=0.004) and curcumin (-10.1%, p=0.02). After 24 months, SAPs continued to decrease significantly in participants taking RQC (-18.7%, p=0.0005) and curcumin (-13.0%, p=0.03). Compared directly, RQC was significantly more effective than curcumin after 24 months (p=0.04). After 24 months, the proportion of responders was 83% in the RQC group and 50% in the curcumin group.
Conclusions :
SAPs are significantly elevated in dry AMD. A decrease in SAPs after oral treatment with RQC indicates that RQC is more protective than curcumin against microvascular disease in AMD. The longitudinal analysis suggests that oral RQC reduces SAPs in vivo and may therefore influence degeneration and progression to advanced disease.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.