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March 14, 2008
What’s the deal with MYODUR
What’s the deal with MYODUR?
It is more than frustrating to hear about something, something that may help and then nothing. You wait and wait, each day looking at your son, wondering if there is something, anything out there, that may be useful.
For several years, there was talk about a compound referred to as Myodur and then all discussion stopped and Myodur dropped off the face of the earth.
Here’s how all this started and how it has evolved over time.
PPMD is dedicated to finding orally available compounds that would slow or halt muscle degeneration. We have been interested in and supporting the investigation of protease inhibitors since 1999.
In 1999, PPMD met with Alfred Stracher, MD. Dr. Stracher had been investigating a protease inhibitor called Leupeptin. In order to improve the effect of Leupeptin, he combined Leupeptin with L-Carnitine, which was eventually referred to as Myodur.
As we began to think about this project, we discussed the need to expand the investigation and compare a number of protease inhibitors to include Stracher’s leupeptin/L-carnitine, as well as, a compound called the Bowman Birk Inhibitor Compound (BBI -C).
With the goal of clinical trial – should we find a significant effect from the investigation – Dr. Stracher partnered with Ceptor. Ceptor began the process of moving Myodur into clinical studies. Unfortunately, animal data suggested Myodur was not effective and the company was unable to get sufficient funding to continue.
That is the bad news. But the good news is that the BBI Compound data was impressive. Data suggested benefit in the mdx mouse. PPMD continued support for the investigation of protease inhibitors, concentrating our efforts on BBI. BBI has been in clinical studies (NIH) in oral cancers. There were no adverse effects. The National Cancer Institute provided the compound for the study and agreed to provide it for a clinical study, but their supply was limited and we needed to establish a supplier, should the clinical study be successful.
BBI is a soy based compound. A company called Solae produced the BBI in collaboration with another company, DuPont. It was at first considered a nutritional supplement, but the FDA ruled that it would need to be considered a ‘drug’. The companies made the decision not to go forward because of the expense involved because of the reclassification of the compound.
That did not stop us. We partnered with PTC to investigate the patent issues and search for a supplier. To make a very long story short, in collaboration with Charley’s Fund, Nash Avery Foundation and the Jett Foundation, another supplement has been identified and tested for BBI activity. HAELAN951 has significant BBI activity, but without a clinical study, we will not know the best way to dose it. It is also very expensive and it will be difficult to get insurance coverage to offset its high cost. PPMD’s and the other foundations’ support for testing and moving forward continues, and our next step will be a clinical study.
FYI – in case you have forgotten those very complicated slides from conferences, here is how protease inhibitors work: Calpain is a primary protease that degrades skeletal muscle. The x-linked gene defect in muscular dystrophy causes an insufficiency of dystrophin leading to poor muscle cell membrane integrity, which allows for abnormal calpain up regulation due to extracellular calcium ion activation.
Calpain exists in every cell of the body and is a protease that degrades cells naturally in a normal metabolic process. When calpain is abnormally up regulated, the cellular degradation process breaks down cells and tissues faster than they can be restored, which is what happens in Duchenne.
The goal is to identify orally available compounds that slow or halt muscle degeneration. The overall goal is to identify compound(s) that have the same (or greater) benefit of steroids, but with lesser side effects. We think a BBI compound may be one piece of the puzzle.
We are working with a number of others to bring this forward.
Please stay tuned.
Posted by ppmd at March 14, 2008 11:45 AM