A groundbreaking clinical trial evaluating a novel gene therapy approach for treating neurogenic bladder in people with spinal cord injury has begun enrolling patients across four centers in the United States. The therapy, developed by biotechnology company EG 427, uses a modified herpes virus to deliver targeted treatment to nerve cells controlling bladder function.
The first patient in the phase 1b/2a trial (NCT06596291) was dosed at Rancho Research Institute of Rancho Los Amigos National Rehabilitation Center in Los Angeles, with additional trial sites in Michigan, Pennsylvania, and Texas.
Novel Mechanism of Action
EG110A is a non-multiplying gene therapy vector derived from herpes simplex virus type 1 (HSV-1). The virus has been modified to eliminate its virulence while preserving its natural ability to travel along nerve pathways and reside in sensory cells near the spinal cord.
"They have modified the herpes virus, which affects nerves, so that it is not virulent and does not multiply, and are relying on its innate ability to travel along nerve cells and reside in the sensory cells by the spinal cord," explained Dr. Argyrios Stampas, lead investigator for the Houston site at UTHealth Houston and TIRR Memorial Hermann.
The vector carries genetic material encoding the active component of botulinum toxin. Once in place, it manufactures this therapeutic protein directly in the spinal cord, blocking the sensory nerve signals that cause involuntary bladder contractions.
"Once the vector is in place, it will manufacture its medication. It will block the sensory signals in the spinal cord that cause reflexive bladder contractions. This is the science fiction stuff that I dreamed about as an undergrad," Dr. Stampas added.
Addressing a Critical Unmet Need
Neurogenic bladder, also called neurogenic lower urinary tract dysfunction, frequently occurs following spinal cord injury. The condition develops because spinal cord damage disrupts normal coordination between the brain and bladder, resulting in involuntary bladder muscle contractions that cause symptoms like urinary frequency, urgency, and incontinence. If left untreated, it can lead to urinary tract infections and permanent kidney damage.
Current standard treatment involves injecting BOTOX® directly into the detrusor muscle of the bladder, requiring as many as 30 injections every six months. In contrast, preclinical studies suggest EG110A could provide relief lasting several years from a single treatment course.
"When people living with spinal cord injury are surveyed, bowel and bladder issues are their top priority," noted Dr. Stampas, who serves as director of Spinal Cord Injury Medicine Research at TIRR Memorial Hermann. "The opportunity to have one procedure that could relieve incontinence for years would be a huge improvement on their quality of life."
Trial Design and Patient Eligibility
The 52-week dose-escalation study aims to enroll 16 adult patients with neurogenic bladder due to spinal cord injury that occurred at least 12 months before screening. Eligible participants must be between 18 and 75 years old, have persistent urinary incontinence despite standard therapy, and regularly perform clean intermittent catheterization.
Participants will receive a single treatment course consisting of multiple intradetrusor injections of EG110A. The therapy will be administered across three dose levels (low, medium, and high) to determine the optimal dose for future studies.
The primary outcome measure is the incidence of treatment-emergent adverse events, while secondary measures include changes in urodynamic variables from baseline to weeks 12 and 52. Participants will also maintain a 7-day bladder diary recording incontinence episodes, daily catheterization rates, and volumes.
Because this is a first-in-human study, patients will require an overnight hospital stay after receiving the bladder injections. The trial includes a five-year safety follow-up period, and visit-related expenses are reimbursed. The investigational therapy has received clearance from the U.S. Food and Drug Administration.
Potential Impact
If successful, this gene therapy approach could represent a paradigm shift in treating neurogenic bladder, offering a long-lasting solution with a single procedure rather than repeated invasive treatments. The technology may also have implications for other neurological conditions affecting bladder function.
According to EG 427, "EG110A is a non-replicating HSV-1 vector that has been designed to selectively silence the signals of key bladder sensory neurons responsible for the bladder muscle overactivity, whilst preserving motor neuron and retaining normal bladder function."
This innovative approach highlights the growing potential of gene therapy to address complex neurological conditions by leveraging modified viral vectors to deliver targeted therapeutic effects.
