ICA @ AUA on Monday, May 16

How long has it been since you heard the word breakthrough? 

Today was a big day on interstitial cystitis (IC) at the American Urological Association (AUA) annual meeting, with ICA Medical Advisory Board member Rob Moldwin, MD’s popular course, two podium sessions devoted entirely to IC, and big news that didn’t even come from an IC session. There were studies about markers, IC physiology, phenotyping and etiology, genetics, and new treatments. On our website, you’ll soon be able to read a summary of every study related to IC. Here are some of the highlights of this exciting day in Washington, DC:

Yes, we heard the word “breakthrough” about a new IC treatment approach!

“If this really works it would be a breakthrough for the therapy of pelvic pain, especially in females,” said Prof. Wolfgang Weidner after he heard Aisha Taylor, MD’s presentation of Northwestern University research on a potential probiotic. Dr. Taylor works with Multidisciplinary Approach to Pelvic Pain (MAPP) researcher David Klumpp, PhD. This team, which is researching  the relationship between pelvic pain and urinary tract infection (UTI), found that if they treated a nasty UTI in mice with an antibiotic, the infection went away but the pain didn’t. Then, they instilled a harmless version of the same bacteria into the bladder or vagina, and not only did the infection stop, but also the mice didn’t show any signs of pain.

That means that we might see a probiotic in a vaginal suppository that could do the job that invasive procedures or strong painkillers do now. There’s a lot of testing to be done to see if this could be developed into a real treatment for patients, but Dr. Klumpp is very positive about the potential of this approach. Don’t miss our interview with him about it the Summer issue of the ICA Update.

Promising drug may stop IC pain without opioids

Italian researcher Prof. Massimo Lazzeri has been studying a new type of drug that acts like an opioid, but isn’t. Nociceptin/orphanin FQ (N/OFQ) is a naturally occurring peptide with a structure similar to opioids; however, it doesn’t bind to the opioid receptors. It has a lot of actions throughout the body, playing roles in everything from pain and anxiety to learning and feeding. Because it is known to inhibit the voiding reflex in rats, Prof. Lazzeri and his team tried it in a small number of patients for whom nothing else worked. (These patients didn’t have Hunner’s lesions, however.) They got bladder instillations of the drug twice a week for four weeks. Although their scores on the O’Leary-Sant Symptom Index didn’t go down significantly, their scores on the Problem Index did, but their pain scores made an impressive drop from about 7 on a 10-point scale to 4, and the scores were still significantly 12 weeks after treatment began. In the 15 patients they could still follow up a year later, 7 didn’t need anymore drugs. N/OFQ and drugs like it might provide an entirely new approach to treatment.

New cannabis-related drug on the horizon

A new cannabis-related compound called GP1 attaches only to one kind of cannabinoid receptor—apparently the critical one for making a difference in bladder pain. It reduced the severity of pain from bladder irritation in mice and also inhibited inflammation. We hope to be hearing more about this compound in the future.

Cyclosporine looks good for severe IC with surprisingly few side effects

The immunosuppressant cyclosporine is included in the new AUA clinical guidelines for IC as a fifth-line treatment. John Forrest, MD, in Oklahoma and Deborah Erickson, MD, in Kentucky used it as a treatment for 22 patients with very severe IC—most (60 percent) had Hunner’s lesions, 3 had bleeding bladders, all had small bladder capacities, and 6 also had autoimmune conditions. With a dose slightly lower than the first IC studies done with this drug, 15 of the patients had a 75% improvement in their symptoms in three and a half months. Only four patients stopped the drug because of side effects.

Gene therapy for bladder inflammation and pain could become a reality

Naoki Yoshimura, MD, PhD’s team at the University of Pittsburgh has been using viruses to carry genes into the bladder wall, first for enkephalin, the body’s own opioid, and now for a TNF alpha blocker, which inhibits inflammation. The team aims to use a combination of the two, to knock down both pain and inflammation, and hopes to conduct trials in IC patients down the road. If a gene therapy like this works out, IC patients could get relief of pain and other symptoms without the side effects of medications or any invasive treatments.

Genes influence IC, but individual environmental factors mean more

How much IC can be attributed to genetics and how much to the environment? It’s about 26 percent for genes and 74 percent for the environment—that is, a unique environment. John Kreiger, MD, and his team drew that conclusion from a study they did in a large database of twins in the state of Washington. The differences in the rate of IC in identical twins versus fraternal twins can give you an idea of how strong the genetic influence is in the population. Although there was clearly genetic influence, it wasn’t huge, and there also wasn’t a correlation between IC and living in the same environment, as twins growing up together do. That means the really strong influence on the risk of having IC is something unique to the individual. The results of this study are very similar to the recent Swedish twin study that we told you about in our articles on pregnancy and IC in the Winter 2011 issue of the ICA Update.

Clarity on IC and caffeine murky

ICA Medical Advisory Board members Dr. Moldwin and Barbara Shorter, RD, EdD and their team tried to get to the bottom of what causes coffee flares. They tried a randomized, placebo controlled study by having IC patients volunteer to take either real caffeine tablets or dummy tablets without anyone knowing which was which. There was no difference between symptoms between the patients who got the real caffeine and those who got the placebo, but the team didn’t show whether the patients who volunteered already thought they had a problem with caffeine or not. So, the definitive answer to the question of whether it’s caffeine or something else about coffee that sets off flares for many patients is still to be found.

Honey could hold something good for IC

Prof. Brian Birch at the University of Southampton in England looked at the effect of honey on bladder mast cells. His team measured histamine release from bladder mast cells that had been pretreated with various honeys and then exposed to a mast cell activator. The honey inhibited histamine release, some varieties performed better than others. Honey also seemed to protect the bladder from damage by a strong acid. Prof. Birch is not sure what it could be in honey that has these effects, but a collaborator will be working on separating out the honey components to find what works.

Pentosan polysulfate may not have pussycats purring

The effect of pentosan polysulfate (Elmiron) was questionable as a treatment of cats with IC. Researchers found that pentosan polysulfate didn’t work any better, and even a little worse, than a placebo for cats with a form of IC. It turned out that the environment the cats were housed in made a difference in their symptoms and made interpreting the results of the study very difficult.

Posted May 17, 2011