A unique, preclinical research collaboration at The Ohio State University Wexner Medical Center may shed light on the reasons why people with spinal cord injuries (SCIs) are prone to frequent urinary tract infections (UTIs) – and therefore at risk for potentially serious health complications.
Thanks to a two-year, $400,000 grant provided by the Craig H. Neilsen Foundation, the researchers are working to identify whether SCIs cause a degree of immunosuppression, making it harder for the body to fight UTIs. They’re also studying whether intravesical therapies can help prevent or treat UTIs with fewer risks than standard treatments.
Ultimately, the team’s goal is to improve the quality of life among patients with SCIs while simultaneously reducing UTI-related hospitalizations.
Addressing a significant but understudied comorbidity
For the 80-90% of people with SCIs who develop neurogenic bladder, recurrent UTIs are a major burden. Not only are they the most common reason for emergency room visits and hospital admissions among this patient population, but they can lead to life-threatening conditions such as sepsis and kidney failure. Recurrent UTIs also require long-term or frequent antibiotic treatment, increasing the risk of antibiotic resistance and problems within the gut microbiome.
Ohio State urologist Iryna Crescenze, MD, one of the study’s co-investigators, says that while mechanical factors increase susceptibility to bladder infections, that’s probably not the whole story.
“We think the higher rate of UTIs among people with SCIs is multifactorial,” she says. “There is certainly a higher risk of UTIs among any patient with bladder dysfunction, such as trouble emptying the bladder. But some data suggests that molecular and cellular changes occur in the bladder following an SCI. Although these changes are thought to increase the bladder’s vulnerability to infections, they’re poorly understood.”
To that end, Dr. Crescenze and her colleagues – including principal investigator Dana McTigue, PhD, director of Research at Ohio State’s Belford Center for Spinal Cord Injury, and co-investigator Phillip Popovich, PhD, director of Ohio State’s Center for Brain and Spinal Cord Repair – are exploring this theory using novel, clinically relevant mouse models.
Finding new molecular targets for therapeutic intervention
To better understand the landscape in which UTIs occur – and whether there’s an impaired immune response following SCI – the team will induce UTIs in SCI mice and normal mice. Then, they’ll measure the immediate and delayed immunological and histological changes that occur within each.
“These efforts will help us compare the inflammatory response in infected mice with and without SCI, while conversely studying bladder pathophysiology after SCI in both infected mice and noninfected mice,” Dr. Crescenze says. “We’ll also look for markers of inflammation that could be targeted with preventive or treatment strategies.”
The investigators will also use SCI mice to test whether therapeutic agents applied directly into the bladder are a safe, effective alternative to options like systemic antibiotics for UTI treatment in SCI.
“Oral antibiotics are the standard of care for recurrent UTIs, but they’re associated with several adverse side effects, and rates of UTI-related hospitalizations among patients with SCIs have not budged since the 1990s,” Dr. Crescenze says. “However, intravesical delivery maximizes drug concentrations at the site of infection and would be an appealing option for patients who already self-catheterize. So, we’re examining whether intravesical therapy works at least as well as, if not better than, current treatments.”
Building on data showing that intravesical gentamicin reduced the burden of antibiotic-resistant bacteria and the rate of symptomatic UTIs in clinical settings, the research team will add a placebo control and test the effects of intravesical gentamicin versus intravesical saline. And because a recent pilot study showed a significant increase in iron – which aids bacterial invasion and expansion – in people with SCI, the team will also test whether intravesical treatment with lactoferrin reduces UTIs in SCI mice.
“This study should provide the data we need to qualify for federal grants and take our work even further,” Dr. Crescenze says. “This is important because people with SCIs usually rank bladder and bowel dysfunction as one of the biggest challenges they face. By finding better ways to prevent recurrent UTIs, we can greatly improve their overall health and quality of life.”