A modified herpes virus that targets spinal cord nerve cells to treat neurogenic bladder in people with spinal cord injury is underway in a first-in-human clinical trial by UTHealth Houston at TIRR Memorial Hermann.
Neurogenic bladder, also called neurogenic lower urinary tract dysfunction, often occurs after a spinal cord injury. The spinal cord helps coordinate bladder storage and voiding. The neurogenic bladder that occurs after a spinal cord injury can lead to discoordination of normal bladder function, resulting in involuntary bladder muscle contractions which can cause overactive bladder symptoms like frequency, urgency, and incontinence, and can even lead to urinary tract infections and permanent kidney injury.
The therapy is a nonmultiplying gene therapy vector, or transporter, which is a modified form of the herpes virus. This vector carries the gene encoding the active part of botulinum toxin, which it will make in the spinal cord to block the sensory nerve signals that result in involuntary bladder contractions. The therapy is named EG110A by its developer EG 427, a biotechnology company.
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. 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."
Argyrios Stampas, MD, MS, lead investigator for the Houston site of the trial and associate professor, Department of Physical Medicine and Rehabilitation in McGovern Medical School, UTHealth Houston
Current treatment with BOTOX® for neurogenic bladder requires multiple injections, as many as 30, into the detrusor muscle of the bladder every six months. Preclinical study results showed that EG110A could last for several years.
"When people living with spinal cord injury are surveyed, bowel and bladder issues are their top priority," said Stampas, 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."
The 52-week, Phase Ib/IIa clinical trial will enroll people from 18 to 75 years of age who are at least 12 months post-spinal cord injury. The trial includes a five-year safety follow-up period. Because it is a first-in-human study, an overnight hospital stay is required after the bladder injections. Visit-related expenses are reimbursed. The drug has received investigational new drug clearance from the U.S. Food and Drug Administration.
Houston is one of four sites across the country for the study. The others are Rancho Los Amigos National Rehabilitation Center in Los Angeles; University of Michigan Rogel Cancer Center in Ann Arbor, Michigan; and Sidney Kimmel Medical College in Philadelphia.
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