IGF-1 Does Look Promising

This last Saturday the KDA chat room's guest was Dr. Maria Pennuto from the Department of Neuroscience at the Italian Institute of Technology in Genova, Italy. Maria is also a 2009 recipient of a KDA research grant. Her current work with insulin-like growth factor 1 (IGF-1) looks very promising for a treatment of Kennedy's Disease.  This research is based upon results that Maria discovered when she worked at NIH.  She found that a specific modification of the mutant androgen receptors results in decreased toxicity.  This modification was due to the activation of an enzyme known as AKT. I felt her work is important enough to include a portion of Maria's chat in today and Thursday's articles. Please understand that since I am not a doctor or researcher, whenever I give an explanation it is only my interpretation of the information provided and I might not explain everything correctly.

"IGF-1 for muscles" shows a great deal of promise in mouse models. The original study was on mice that had the defective gene, but were not showing symptoms yet. In these mice, the IGF-1 reduced the amount of androgen receptor present in the cells and therefore delayed the onset of Kennedy's Disease and slowed the progression once symptoms began to show up. The current study at the National Institute of Health (NIH) is using mouse models that have shown symptoms. Researchers are trying to determine if IGF-1 still works, works to a lesser degree, or does not work at all once Kennedy's Disease symptoms are present. This current research will also help determine the viability of IGF-1 in humans.

A little background information might be useful here. Cells from a person with Kennedy's Disease have a problem cleaning the residual caused by testosterone within the androgen receptor (AR). The cell's nucleus actually rejects the AR when it tries to enter it for cleaning. Because of this, the AR cannot free itself from the residuals (garbage) that are clinging (binding) to it. Eventually, the AR becomes so clogged that it can no longer function and dies.

To give you a more common example to explain what is taking place, it is like having an engine with a clogged oil filter. The oil becomes so gummed up over time that it can no longer do its job and the engine eventually malfunctions and dies. IGF-1 appears to allow the androgen receptor to clean the garbage caused by testosterone buildup thereby keeping it healthy and able to do its job. Using the same oil filter example, if you keep the oil filter clean so it can do its job, the engine will run better and last a long time.

Something else came out in the chat that was interesting. Many of us with Kennedy's Disease have wondered which came first, the chicken or the egg (e.g., how did Kennedy's Disease actually start especially in a family lineage)? According to Maria, the CAG part of our DNA is somewhat fragile and almost any abnormality can change the number of repeats. In other words, a family with no history of Kennedy's Disease could all of a sudden have one or more children with the defective gene. I had always assumed that somewhere in a family's history was a carrier.

The KDA has a saying when it comes to supporting research.

"Working together to find a treatment or cure

… for our generation, and for our children and grandchildren."

Even though it looks like IGF-1 will not be viable for us "more elderly" gentlemen (aka old codgers), it does look promising for those not showing any symptoms and possibly those who are in the early stages of Kennedy's Disease. As a parent, I believe that would be a tremendous step in the right direction in minimizing the impact of Kennedy's Disease on future families.

Meanwhile, we patiently wait the results of future testing and hope for a clinical trial. For someone that is not known for having a lot of patience, these waiting periods seem like an eternity.