Michael B. Chancellor, MD
|
A: Botulinum toxin is fascinating because it is not only the world's most potent toxin but also the world's most potent medicine.
Over the past 200 years, people died from botulism as a result of bad canning. Over time, the bacterium that causes botulism
became isolated and purified. In the 1980s, an ophthalmologist, Dr. Alan Scott, decided to use this purified substance, botulinum
toxin, for the treatment of blepharospasm. It was approved by the FDA in 1989. So botulinum toxin, although still under investigation
for urologic indications, has been approved by the FDA for over 20 years now for other medical uses. It should be noted that
using botulinum toxin for urologic conditions is considered off-label use.
The process by which this biological neuromodulator works is incredibly elegant. It has one of the highest affinities of any
chemical or biologic ever discovered, meaning that even the smallest amount presented to a nerve terminal will irreversibly
bind to the presynaptic neuronal membrane, enter the cell, and block specific Soluble NSF Attachment Protein Receptor (SNARE)
proteins that would normally allow the release of the neurotransmitter that's essential for all muscle and sensory neuropeptide
release.
Q: Let's talk about the use of botulinum toxin in overactive bladder. Is it important to distinguish between neurogenic and
idiopathic overactivity for the purposes of this discussion?
Philip M. Hanno, MD, MPH
|
A: That's a good question and one that has been brought up before. I started using botulinum toxin for OAB over 10 years ago,
and there was no commercial interest at that point. We treated not only neurogenic overactive bladder but also the idiopathic
overactive bladder, and in my experience, botulinum toxin works equally well, regardless of the pathology of OAB.
Q: How does botulinum toxin work in OAB? Do we know whether nerve growth factor produced in the urothelium is actually excreted
in the urine?
Michael B. Chancellor, MD
|
A: Yes, it is. Nerve growth factor (NGF) is the prototypical neurotrophic factor. It's critically important in the maintenance,
function, and survival of nerves, especially the sensory nerves. It's made in the urothelium and the detrusor muscle to maintain
their normal innervation. It's helpful that the protein can be excreted in the urine and, via ELISA assays, we can quantitate
it. Dr. Hann-Chorng Kuo and associates in Taiwan have checked urine NGF levels in neurogenic and idiopathic OAB patients treated
with botulinum toxin, and they found a significant decrease in the urine NGF level 3 months after treatment, but only in responders.
Non-responders did not have a change in their urine level of NGF.
NGF implies neuroinflammation and abnormal nerve function. If the NGF level changes, you know the treatment is having a significant
effect. The correlation between responders and non-responders is very exciting.
Practice Tools
