Jeff, if you mean you won't change my mind that there is high level gamesmanship always happening in this community, you are right, you will not change my mind. If that ever involves any community input.. the answer is it doesn't.

I see things differently.

First, I don't see the relevance of the antioxidant review study to people in the HD community taking creatine or CoQ10 or eating antioxidant rich foods. The review looked at studies with healthy people and studies in which antioxidants were intended to help with disease. The antioxidants chosen in the review were Vitamin A and beta-carotene, Vitamin E, and selenium. Vitamin A and beta-cartene carried an increased risk of mortality, Vitamin E had no effect, and selenium resulted in reduced mortality. So obviously, all antioxidants don't have the same effect. And even with Vitamin A, some of the people in those studies were taking more than ten times the upper limit for tolerability which certainly seems unwise.

The review is also biased in that it included 68 studies but excluded over 400 which otherwise met the criteria because no one died. If one is going to look at the effect of taking antioxidants on mortality, I would think studies in which no one died would be of great interest!

Second, I am not at this time concerned about the effect of antioxidants on autophagy. There isn't any credible evidence in the HD mice that autophagy upregulation increases survival time. Rubinsztein and colleagues have evidence that two autophagy inducers, rapamycin and rilmenidine improve behavioral deficits in the R6/2 mice but there is no survival data (this may be due to different animal testing regulations in the UK, I believe that the researchers are required to euthanize them at a point in the disease process). It's possible that the behavior improvements are due to upregulated autophagy in muscles and not in the brain.

A number of authors have expressed concern that more needs to be learned about the role of autophagy in cell death and caution that upregulating autophagy could be a two edged sword. So I'd like to see this issue explored some more.
[www3.interscience.wiley.com]

And if the Albert Einstein College of Medicine researchers are correct the process of autophagy itself is impaired and the autophagosomes are not recognizing the HD protein as well as abnormal lipids and depolarized mitochondria as cellular garbage that needs to be cleared away and digested. It could be that what needs to be done is to stop the interaction of the HD protein with the autophagosomes; if autophagy isn't working, upregulating it won't help.
[www.hdsa.org]

I do think that we have solid evidence that oxidative stress as well as reduced cellular energy play major roles in HD pathology. I also think we have a lot of good data about creatine in mice and promising Phase I and Phase II trials. I am encouraged so far and look forward to the results of the Phase III trial.

There is uncertainty with whatever we chose to do. If we try something such as creatine or memantine or any other promising drug or compound which has not been studied in Phase III trials for HD patients, there is always the possibility that we could encounter unexpected side effects. If we participate in a promising clinical trial, it could still fail and again there could be unexpected side effects. If we take an approved drug we might experience a rare side effect or there may be side effects that only appear with long term use. All we can do is decide on the risk benefit ratio we are comfortable with, do our homework on what is currently known and talk over potential treatments with our doctors.

Thank you Marsha and Eric, for looking after our best interests, and not treating some of us like we're stupid. And at least i know, if i ever ask marsha or eric a question, they will answer it for me. Lavonne hasnt answered my questions yet, and on the other thread, hasnt even adknowledged the link that i posted to her about ethniticity and hd. Oh well.

Marsha, i really like your post, you put a lot of work into that.



Edited 1 time(s). Last edit at 07/06/2010 05:21PM by Barb.

Jeff, you should re-write that response and post it. Even if you think your position is so different from Erics that you can't "change" his mind - there are many people here reading this with much interest and want to hear what you have to say! Please post your response, I am sure I am not the only one who wants to hear what you have to say.

Jeff a lot of this stems from the hd ready campaign that chdi did last summer, that really tried to take us all for stupid...i don't think you were on the forum then Jeff, so i know you dont know that part of it. Chdi cared more about any way they could to get peoople to do trials, than they cared about the people themselves.



Edited 1 time(s). Last edit at 07/06/2010 08:33PM by Barb.

Bravo Eric. But Sarah said it best and I agree with her that I want and need to hear everyone's opinions. Everyone has their own viewpoint and perspective. There is room for all voices here.

There IS room for other voices here you're right.. beware of people who say one thing, then another later is all...people we rely on.

Barb-

For the record, "HD Ready" was not a CHDI initiative. I don't know what leads you to you think it was.

Notwithstanding that I don't think the intention of the program was to treat anyone as "stupid". I would be interested in hearing about why you, or anyone else on this board, thinks that was the case. Certainly not something we would ever want to do, even inadvertently.

Thanks,

Robi

Robi Blumenstein
CHDI Management/CHDI Foundation
robi.blumenstein@chdifoundation.org
www.chdifoundation.org

The bottom line is that everyone on this list wants to find treatments for HD. And we want all of these organizations -- whether it's big pharma, academic HSG (and EHDN) centers, CHDI: the more the better. Just like all the good people on this list, We can't expect that these organizations will agree on the best way to proceed. I think all of these organizations (though they may have other agendas too) want to help the HD community.

One thing we, and they can agree on is that clinical trials will be the only way to make progress toward treatments for people. While nobody knows which clinical trial will be successful, I think it important to have discussion about the pros and cons of each trial so each of us can make informed decisions.

My "short list" of points I think important:

(1) Scientific rationale (with both positive and negative studies described).
(2) For Phase 3 trials: Peer-reviewed and published phase 2 results
(3) Documentation that the drug gets into brain

And other general considerations:

(4) Feasibility of completion of a trial -- this is an important thing that should be factored into long trials.
(5) With limited number of participants, a long trial will limit and slow enrollment in other trials. This is one of the reasons that drug companies are going to Europe first.

(5) With limited number of participants, a long trial will limit and slow enrollment in other trials.

So there shouldnt be any long trials, just so you can get your short trials in??? Or people should be able to choose what trial suits them best?

Robi, you can do a search on that, by hitting the search button at the top of the forum, if your memory escapes you lol i really dont remember everything about it either, old story, old news, we can move on, maybe lol

Lavonne, Barb asked you a valid question, and I see you are back on this thread again.. could you please answer her question? I am also interested. Was all your research for naught? You now diregard you push on suppliments and why?



Edited 1 time(s). Last edit at 07/08/2010 06:18AM by mrspatwolf.