Enhancing Recovery of SCI-Induced Bladder Dysfunction Using Small Molecules
Abstract
The p75 neurotrophin receptor has been shown to be involved in various neurodegenerative conditions and our preliminary data indicate that it is also involved in bladder complications resulting from spinal cord injury (SCI). LM11A-31 prevents activation of degenerative signaling while promoting nerve regeneration pathways. Preliminary findings demonstrate that daily oral administration of LM11A-31 is the first agent that treats both neurogenic detrusor overactivity (NDO) and detrusor sphincter dyssynergia (DSD) in mouse models. These effects could be translated in SCI patients to decrease NDO, incontinence, catheterization, urinary tract infections, DSD and kidney damage to improve the health and quality of life of SCI patients. Accordingly, we propose to study the therapeutic benefit of LM11A-31 in male and female complete and partial SCI mice assessed using a range of physiological and molecular techniques. Both complete transection and contusion injuries will be evaluated as the pathological outcomes can vary significantly depending upon the extent of injury. Further, the neural regenerative properties of the tropomyosin related kinase receptor agonist, LM22B-10, will be evaluated in combination with the protective effect of LM11A-21. Our preliminary data demonstrate the efficacy of LM11A-31 treatment in complete SCI and we hypothesize that there will be even more beneficial effects in spinal contusion-induced bladder dysfunction.
Document Details
- Document Type
- Technical Report
- Publication Date
- Nov 01, 2021
- Accession Number
- AD1190691
Entities
People
- Anthony J Kanai
Organizations
- University of Pittsburgh