Oral Administration of the p75 Neurotrophin Receptor Modulator, LM11A-31, Improves Erectile Function in a Mouse Model of Cavernous Nerve Injury

BackgroundRadical prostatectomy for prostate cancer can not only induce cavernous nerve injury (CNI), but also causes hypoxia and structural changes, which lead to a poor response phosphodiesterase 5 inhibitors.AimTo investigate the therapeutic effect of oral administration LM11A-31, small molecule p75 neurotrophin receptor (p75NTR) ligand proNGF antagonist, in mouse model bilateral CNI, mimics injury–induced erectile dysfunction after radical prostatectomy.Methods8-week-old male C57BL/6 mice were divided into sham operation CNI groups. Each group was 2 subgroups: phosphate-buffered saline LM11A-31 (50 mg/kg/day) being administered once daily starting 3 days before via gavage. weeks we measured function by electrical stimulation nerve. The penis harvested histologic examination Western blot analysis. major pelvic ganglia cultured assays ex vivo neurite outgrowth.OutcomesIntracavernous pressure, neurovascular regeneration penis, or functional evaluation, cell survival signaling measured.ResultsErectile decreased (44% group), while led significant improvement (70% group) association with increased content, including endothelial cells, pericytes, neuronal processes. Immunohistochemical analyses showed significantly p75NTR expression dorsal mice, attenuated treatment. Protein active PI3K, AKT, nitric oxide synthase increased, death c-Jun N-terminal kinase Furthermore, promoted sprouting lipopolysaccharide exposure.Clinical ImplicationsLM11A-31 may be used as strategy treat men diseases.Strengths & LimitationsUnlike biological therapeutics, such proteins, gene therapies, stem clinical application would likely relatively less complex low cost. Our study has some limitations. Future studies will assess optimal dosing duration compound. Given its plasma half-life approximately 1 hour, it is possible that more than per day provide added efficacy.ConclusionSpecific inhibition proNGF-p75NTR degenerative represents novel induced injury.Yin GN, Ock J, Limanjaya A, et al. Oral Administration Neurotrophin Receptor Modulator, Improves Erectile Function Mouse Model Cavernous Nerve Injury. J Sex Med 2021;18:17–28.