Grant Duration
11/19 – 12/25
In 2025, We combined omics-based profiling (proteomics/lipidomics) with practical serum biomarkers (IL-6, IL-10) to guide dosing using LPS-free rHsGal-1, while improving immune phenotyping to clarify how age, muscle, sex, and treatment influence inflammatory cell states
Our lipidomics analyses indicate that Bla/J psoas displays clear lipid dysregulation relative to WT, including reductions in several sphingolipid and membrane phospholipid classes. Importantly, rHsGal-1 treatment produces a distinct lipidomic state consistent with lipidome reprogramming, Together, the proteomic and lipidomic signals provide converging evidence that rHsGal-1 may modulate pathways linked to membrane composition, oxidative stress, and metabolic adaptation in diseased muscle.
We refined a simple blood-based approach to help choose the best rHsGal-1 dosing schedule. After dosing, IL-6 changed quickly (~2 hours) and IL-10 changed later (~day 4), creating a practical two-time-point readout. Next, we will use this framework to compare dosing schedules side-by-side and relate these biomarker patterns to immune and tissue outcomes.
In our immune phenotyping work, we found early signs that rHsGal-1 may help “rebalance” immune activity toward a less inflammatory state, in both male and female mice, supporting our broader goal of reducing the chronic inflammation linked to disease.
Baseline disease profiling also showed that immune infiltration in muscle is elevated in Bla/J compared to WT in psoas earlier than expected, and that the magnitude and composition of macrophage subtypes vary by muscle, highlighting the importance of considering muscle type and age when interpreting treatment effects.
Together, these advances position us to more reliably quantify immune cell state changes across age, sex, muscle, and regimen conditions in upcoming studies, and to connect immune shifts with proteomic, lipidomic, and serum biomarker signatures.
Given the dynamic nature of inflammation throughout the disease stages, we aim to characterize macrophage and neutrophil populations, alongside IL-6 and IL-10 levels, in untreated and treated Bla/J and WT mice between the ages of 3-12 months of age. This will help us evaluate how rHsGal-1 affects inflammation and systemic cytokine modulation across different disease stages. Building on these promising findings, we aim to optimize the dosing regimen of rHsGal-1 by monitoring changes in serum cytokine levels. These studies will enhance our understanding of rHsGal-1’s effects, including its influence on inflammation, membrane repair, and ambulation, positioning it as a promising therapy for LGMD2B.
