Importantly, HS replacers such as heparin, PI-88 and BT548 profoundly inhibit the catalytic activity of recombinant human heparanase (S4 Fig), suggesting that as dual activity drugs, they could represent a new class of therapeutic for restoring beta cell HS and blunting or preventing the progression of T1D. The gene discussed is HPSE; the disease is type 1 diabetes mellitus.