There are a couple things in phase 3 correct? So when do they determine if something works or not? After completion of phase 3? Is there any hope for the therapies in phase 3 now?

So many questions!

We have an update to the research pipeline coming so some of those things will change. We hope to expand on the pipeline and research section during the coming year which we hope you will find useful.

In a nutshell treatments are determined to be successful if results reach a certain level of statistical significance. Then it becomes available to us if the FDA approves it. There are a lot of challenging hurdles for our researchers to overcome in order to achieve FDA approval.

I think there always hope for research in phase 3, but I'm most excited by what Isis Pharmaceuticals is doing in the area of gene silencing. We feel it's our best bet for a significant treatment.

Which research are you most interested in?

Steve

I am interested in whatever will cure this disease! It is do scary living at risk.

I pray that they find something that will work.

Everyone is so hopeful for Gene Silencing. I really hope it works too. However, if it does not work is there still hope that something out there will help this disease? Also, if so many different things have helped HD mice in the past and been largely unsuccessful in humans, what makes scientists believe that gene silencing has such a large potential to help HD. I am not trying to be negative. In fact, I pray almost every second of the day that gene silencing will work for HD. My husband is at risk and I love him to the moon and back. I just want to know why gene silencing seems so much more promising to the community than other drugs or therapies that have been tried in the past. I just don't want to put all my hope in something and then get crushed if it does not work. I also hope scientists have a back up plan just in case this does not work.

Great question! I would like to know also! I don't think any of the other therapies were to turn off the gene so I think since gene silencing would turn off the gene that's why this could work. Just my thought though.

Gene silencing has worked in cell models and in mouse models. There is every hope that one of the different techniques will work in humans. I was in a Phase 1b safety trial for Selisistat, a SIRT1 Inhibitor. That drug is in a Phase 2 trial in Europe, to be followed with one in the US.

Another technique being pioneered by Isis uses something called ASO - antisense oligonucleotides. This also has worked in cell and animal models.

No one can tell you exactly when Phase 3 trials will be completed, but there is every hope that one or both of these gene silencing therapies will work. Be patient! We have a ways to go, but we've come a long, long way in the past couple of years.

Will

I can't think of a drug which has failed in Phase III trials that had actually worked in the mice. Thinking of failures.... Back in the 90s there as an antioxidant which failed in trials, but that was before we had mouse models. CoQ10 wasn't successful over a decade ago; the trial was planned before the mouse models. The results showed a modest slowing of progression which is why CoQ10 is being tried at a larger dosage. Since then, it has been tried in mice with some mixed success. In my opinion, I don't think the issue of bioavailability in the brain has been settled so I have no prediction about how the trial will go. Creatine has been tried in the mice with success and is now in Phase III trials. Based on how it reduces a biomarker for antioxidant damage in Phase II trials, I think there's a good chance it will work.

Dimebon was not tried in the mice. There was an AD trial here in the U.S. based on reportedly good results in Russia. An HD researcher asked the company to also try the drug for HD. I wrote about this here: [www.hdlf.org]

Gene silencing isn't the only promising treatment in the pipeline. GM1 or a derivative is very promising and researchers are planning clinical trials. Paul Muchowski's JM6, a KMO inhibitor is also very promising and he too is planning on clinical trials. I think those are the two most exciting possibilities other than gene silencing.

There are a couple of potential treatments being tried for other diseases which might also become HD treatments: methylene blue and phosphodiesterase inhibitors.