• The current clinical trial ... results should be published in the next few weeks.
  
• Three potential clinical trials
  
• Reviewed some other clinical trials that have taken place
  
• And, provided a little 'doctorly' advice on questions asked and commented on certain types of research.

• A few years ago we mailed out educational flyers to over 10,000 neurologists
• The tissue donation program
• Medical Information Form
• Smart Exercise Guide
• Society Security - Disability Application Guide

quote:

At that meeting, I described the direction of our research and how we are focusing on a particular aspect of androgen receptor (AR) function. Two papers were recently published indicating that other scientists are finding the same thing. Specifically, that the mutant form of AR is altering the ways genes are turned on.

… there are different approaches to therapy and let me address them one at a time. First, autophagy. Yes, I think this is a promising avenue for KD, but not in the immediate future. Several different autophagy inducers are in development but there are no clinical trials underway yet. Autophagy is a cell process for degrading things inside the cell that are unwanted. Like clumps of toxic AR for example. It is a natural process, but the idea is to boost it with an autophagy inducer. This has been shown to work for a number of diseases using animal models (including KD).

The second approach mentioned is stem cells. There will be a big boost in stem cell research now that the ban on federal funding has been lifted. And I anticipate that we will begin seeing application of stem cell therapy for some diseases (like diabetes and hemophelia) in the near future. We dream of treating neurological diseases with stem cells, and some investigators have successfully turned stem cells into neurons, even motor neurons, but delivering them to the right location is the difficult part. There is active work on this, but I see that as a tough obstacle.

The first generation of autophagy inducers were all based on a single target (called TOR, by the way) and in animals autophagy can be successfully induced without adverse effects that we are aware of. But there are theoretical concerns specifically, that these drugs also produce immune suppression. This is not a problem in animal trials in the short term because they are on the drug for about 6 months. The concern is that humans with KD or similar disease would need long term therapy so a second generation of drugs has been developed that work differently use of the second generation drugs in animals is limited so far my colleagues at Penn applied to perform a clinical trial of an autophagy inducer (first gen) in humans with Parkinson disease, but were turned down because it was felt that there was not enough animal data yet.

The third approach is targeting AR directly and specifically. This would only apply to KD. That is the idea behind the dutasteride and lupron trials. I will say that I believe that the most promising approach will be targeting AR directly. And this is supported by the two papers just published - one by Dr. Kato in Japan and another by Diane Merry at Jefferson. We will have a paper on this soon too.

Many of you know that we use a fruit fly model of KD. We have used this model to examine over a dozen different parts of the AR protein to find out which ones are responsible for driving neurodegeneration. We have taken over a dozen different forms of AR (each with a targeted mutation that we introduced) and made transgenic flies
Hard physical exertions can be counterproductive in KD. We have identified three targets in the AR protein that are involved in causing the toxicity.

In all of these diseases, the final common pathway appears to be the way the disease protein influences the process by which genes are turned on and off - called transcription. So...we believe that we have found a critical target and to prove it we are now testing this in a mouse model.

A human trial is a very big deal. Let me tell you why we approach this with caution... First, you need to have a promising therapy, meaning preclinical evidence that it will probably work and also evidence that it will probably not be toxic to the subjects. There are risks involved. Beyond the obvious concern about risk to the subjects (e.g. dangerous side effects), there are risks that a poorly run trial can kill a promising therapy. There are also opportunity risks to a clinical trial since it is only practical to run so many and we must make the most of these limited chances.

quote:

Originally posted by Bruce:
The Slide