Targeting neurotrophin and nitric oxide signaling to promote recovery and ameliorate neurogenic bladder dysfunction following spinal cord injury -Mechanistic concepts and clinical implications

This review summarizes the presentations made to a workshop entitled "Targeting Neurotrophin and Nitric Oxide Signaling to Promote Recovery and Ameliorate Neurogenic Bladder Dysfunction following Spinal Cord Injury - Mechanistic Concepts and Clinical Implications" at the International Continence Society 2022 Vienna Meeting. Spinal cord injury (SCI; T8–T9 contusion/transection) causes impaired mobility, neurogenic detrusor overactivity (NDO), detrusor sphincter dyssynergia (DSD) and decreased quality of life. The workshop discussed potential therapeutic agents to mitigate the lesion and its consequences, including strategies to reduce lesion severity and manage lower urinary tract (LUT) pathophysiology. A trio of agents was considered for lesion attenuation: LM11A-31, a p75 neurotrophin receptor modulator to counter apoptosis; LM22B-10, a TrkB/C activator to promote neuronal growth; and cinaciguat, a soluble guanylate cyclase activator to enhance angiogenesis at the injury site. Targets within the bladder to reduce detrusor overactivity and fibrosis, including purinergic pathways and afferent signaling, were reviewed. Increased mechanosensitive signaling as a contributor to DSD and related drug targets were also considered. Emphasis was placed on targets that help restore function and reduce pathological LUT consequences, rather than downregulate normal function.