muparfostat (PI-88)

Importantly, triple therapy with PI-88, gemcitabine, and Abraxane significantly suppressed tumor growth and prolonged survival relative to all mono- and doublet regimens. Immune profiling revealed that this combination reduced PSC activation, contracted M2 macrophage and regulatory T cell populations, and expanded M1 macrophages, CD8⁺ T cells, and NK cells. In conclusion, these data underscore HPSE as a key driver of fibrosis and chemoresistance in PDAC and support HPSE inhibition as a promising strategy to enhance therapeutic efficacy.

We found that PI-88, a heparan sulfate mimetic, directly antagonized IFN-γ to rescue human OPC proliferation and differentiation in vitro and blocked the IFN-γ mediated inhibitory effects on OPC recruitment in vivo Importantly, heparanase modulation by PI-88 or OGT2155 in demyelinated lesion rescued IFN-γ mediated axonal damage and demyelination...We find that pathological interferon-gamma can be blocked by modulation of the heparanome following demyelination using either a heparan mimetic or by treatment with heparanase inhibitor. These studies establish the potential for modulation of heparanome as a regenerative approach in demyelinating disease.