Early Detrusor Chemodenervation to Preserve Bladder Compliance and Longevity After Spinal Cord Injury
Abstract
Rationale: Spinal cord injury (SCI) is among the most devastating traumatic injuries, and there are approximately 300,000 Americans living with SCI. In addition to the loss of upper and lower extremity function, more than 80% of all patients with SCI suffer from neurogenic bladder, a condition caused by nerve impairment to the bladder and its control muscles (sphincters). Neurogenic bladder leads to increased lifetime health risks for persons with SCI, including urinary tract infection and loss of kidney function, and these complications negatively impact quality of life (QoL). Therefore, new and innovative ways to manage neurogenic bladder and promote bladder health are crucial to the long-term well-being of persons with SCI. Injecting the bladder muscle with botulinum toxin A (BoNT-A) is an approved treatment for urinary urgency, frequency, and incontinence due to neurogenic bladder. This treatment prevents the overactivity and increases bladder compliance (the ability of the bladder to store urine). However, bladder BoNT-A injections, also called chemodenervation, are currently only offered to patients after other treatment options have failed. By that time, often years after the initial injury, permanent bladder muscle changes, such as thickening and scarring, have already occurred. Here, we propose an innovative use of an already approved treatment to examine whether chemodenervation performed early in the recovery process can increase bladder compliance and longevity of bladder health, and reduce muscle thickening, scar formation after SCI. Objectives: In this proposal, we will investigate whether early chemodenervation mitigates deleterious bladder wall changes and preserves bladder storage function following SCI. A rat model of acute SCI will be used to test our hypothesis, as well as answer fundamental questions regarding (1) the optimal therapeutic window for early treatment, (2) how to preserve bladder function over time, and (3) the mechanism of nerve changes that underlie neurogenic bladder development. We hypothesize that chemodenervation will prevent or delay the progressive loss of bladder compliance, thereby preserving bladder health in the chronic stage of SCI. We will also perform a pilot clinical trial and examine the feasibility of treating patients early (<6 weeks) after SCI, and the effects of early BoNT-A treatment on human bladder compliance and tissue changes. Research Impact, Benefits, and Risks: This proposal directly addresses the needs of and treatments for persons with SCI and neurogenic bladder. Bladder function is one of the top health priorities of persons with SCI. Given that almost of all SCI patients suffer from bladder dysfunction (>80%), limiting or stopping the development of changes in bladder tissue will likely have a huge impact on the treatment and care of neurogenic bladder-related complications. By helping to preserve bladder compliance, this intervention will decrease incontinence (leaky bladder), the risk of urinary tract infections, and help to preserve kidney function over the lifetime of a patient with SCI. Moreover, early treatment will likely also increase the longevity of bladder health. These outcomes will go a long way to improving the well-being and QoL for large numbers of persons with SCI. The pilot clinical trial in this proposal will be a feasibility study, to confirm that the effects seen in the rat model will be identifiable in human tissue and in human bladder function. If the results from the pilot clinical trial are positive, we will move to a larger scale multisite randomized clinical trial. We anticipate that the results from such a trial would be available in 5-6 years, indicating whether prevention of neurogenic bladder changes is possible.
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Jan 04, 2024
- Source ID
- HT94252310522
Entities
People
- Zin Khaing
Organizations
- United States Army
- University of Washington