Antagonism of proNGF or its receptor p75NTR reverses remodelling and improves bladder function in a mouse model of diabetic voiding dysfunction

ABUBAKR H. MOSSA; ALBA GALAN; PHILIPPE G. CAMMISOTTO; MONICA VELASQUEZ FLORES; SAMER SHAMOUT; PABLO F BARCELONA; H. URI SARAGOVI; LYSANNE CAMPEAU

DIABETOLOGIA

SPRINGER

Lugar: Berlin; Año: 2020

0012-186X

bstractAims/hypothesis Although 80% of diabetic patients will suffer from voiding difficulties and urinary symptoms, defined asdiabetic voiding dysfunction (DVD), therapeutic targets and treatment options are limited. We hypothesise that the blockadeof the pro-nerve growth factor (NGF)/p75 neurotrophin receptor (p75NTR) axis by an anti-proNGF monoclonal antibody or by asmall molecule p75NTR antagonist (THX-B) can restore bladder remodelling (represented by bladder weight) in an animal modelofDVD. Secondary outcomes of the study include improvements in bladder compliance, contractility and morphology, as well asin voiding behaviour, proNGF/NGF balance and TNF-α expression.Methods In a streptozotocin-induced mouse model of diabetes, diabetic mice received either a blocking anti-proNGFmonoclonal antibody or a p75NTR antagonist small molecule as weekly systemic injections for 4 weeks. Animals weretested at baseline (at 2 weeks of diabetes induction), and after 2 and 4 weeks of treatm