But this group suggested in November 2009 that they were "12 months" from human phase I trials, which have yet to begin. Given that they haven't published efficacy in even a mouse, it's probably safe to assume that their goal of "treating patients in 4 years" will be as successful.by jcarroll42 - Huntington's Disease Support Center
I'm going to stop reading this site - I'm not finding the attitude useful. I'm sorry for the difficulties you all are having, and wish you the best. If anyone needs any thing from me, I can be reached at: jcarroll@cmmt.ubc.ca. I'll be starting my new position in Boston eventually, but shouldn't be tby jcarroll42 - Huntington's Disease Support Center
Eric - Why do you think this is a "long way away"? What information do you have that lets you comfortably suggest this? It's fine for you to be negative for yourself, but people are reading your posts here, so you might as well back up what you say with some data. Here are some facts. Alnylam and Isis both have multi-million dollar projects, supported in part by CHDI, to siby jcarroll42 - Huntington's Disease Support Center
Marsha - I agree with you about antisense. I'd rather use a drug we can stop using if there are safety concerns along the way. Oh wait, I'm biased again. Something we should all be watching closely is the antisense study being done in familial ALS (Lou Gehrig's disease). Isis Pharmaceuticals is running a trial in the US in patients with this genetic form of the disease. More than one patby jcarroll42 - Huntington's Disease Support Center
Hi All, I'm biased - I'm working on allele-specific silencing. But I just wanted to address something Eric said. He compared concerns about memantine and creatine to safety concerns with huntingtin silencing. I don't think they're the same at all. Silencing mutant huntingtin is in a class by itself in terms of potential therapies. No one disagrees with the idea that mutant huntingtiby jcarroll42 - Huntington's Disease Support Center
I'm totally biased, because I'm about to go work on a very similar project in Marcy's lab as a post-doc. But, I think this is exciting stuff. Meclizine is AKA Dramamine, for the curious. But we're a long way from anyone suggesting it'd be helpful in people. Also, the authors note that the effect they are interested in isn't what the drug is "supposed" to do. So if you took enoughby jcarroll42 - Huntington's Disease Support Center
Hi Barb - This is a really good question. Memantine works by blocking glutamate receptors (as you know). How excitable these receptors are changes over the course of the disease in mice. Rona Graham, in Michael's lab with me, has shown that the sensitivity to excess glutamate isn't constant in HD mice but changes over time. So your idea about giving different doses at different times isby jcarroll42 - Huntington's Disease Support Center
Dear Barb - I'm so sorry to hear about your loss.by jcarroll42 - Huntington's Disease Support Center
Dear Barb - I'm so sorry to hear about your loss.by jcarroll42 - Huntington's Disease Support Center
Hi Julie - I think we need to be very careful with memantine before symptom onset. Recent work from a couple different labs suggest that while low doses might be helpful for HD, higher doses might be harmful. "Low" and "high" are kind of fuzzy terms, because these studies were done in mice and we just don't have enough data from human studies to be sure what's right, orby jcarroll42 - Huntington's Disease Support Center
Hi - There was a recently completed analysis of coenzyme-Q10 in a HD mouse model. This study was done by Psychogenics (a mouse testing company), in conjunction with CHDI. CoenzymeQ10 did nothing for the mice in this study. A few other studies, going back as far as 2002, using the same mouse model have showed beneficial effects of coenzyme-Q10. So there is contradictory data at the mousby jcarroll42 - Huntington's Disease Support Center
Sorry Barb, I'm not going to make the meeting, so no suitcase ride this time.by jcarroll42 - Huntington's Disease Support Center
Wow, if it was this easy, you'd think we'd have solved this thing by now. - jeffby jcarroll42 - Huntington's Disease Support Center
But then I left my iPhone in the cab on the way to the airport, demonstrating that I'm really not all that smart.by jcarroll42 - Huntington's Disease Support Center
Will - Close - they're in the second row, both writing intently. Steve has the camera out. jeffby jcarroll42 - Huntington's Disease Support Center
I'm really, truly, baffled by Eric's posts.by jcarroll42 - Huntington's Disease Support Center
Hi Eric, Thanks for your reply. I wrote a long response and deleted it, because our opinions are so different there's not much room for discussion. Ultimately, it seems like you believe that CHDI cares more about running "their" trials than they do about HD patients. I have no idea what would have given you this idea, but I doubt I'm going to talk you out of it. jeffby jcarroll42 - Huntington's Disease Support Center
Hi Eric, I'm curious about this discussion. I don't understand your point - you said: "This new proclamation stabs at the very heart of helping to have a positive attitude when the worst news happens" Which proclamation are you referring to? Thanks, jeffby jcarroll42 - Huntington's Disease Support Center
Hi All, I should have mentioned before that the speaker who sparked this discussion is Jang Ho Cha. Jang Ho is an MD/PhD who has been working almost exclusively on HD for the last 15 years. He was in Venezuela at Lake Maracaibo as a neurologist helping the villagers there, and helping all of us by describing one of the families that contributed to cloning the gene in 1993. Based onby jcarroll42 - Huntington's Disease Support Center
Will - I understand what you're saying about self-directed supplements providing a feeling of engagement. I guess I derive this mostly from my day to day work, so supplements end up being one more thing to worry about, rather than a help. Also, I think you're correct that only you can judge your anecdotal experience with supplements. I find that, as North Americans, we have this tendency toby jcarroll42 - Huntington's Disease Support Center
Hi Will, I don't disagree with you, but have been thinking more about the "can't hurt" idea. The divide between "supplement" and "drug" is basically a legal distinction, not a chemical/biological one. For a long time, people have been taking vitamins (including A&E) and other supplements because they were antioxidants and therefore "couldn't hurt&quby jcarroll42 - Huntington's Disease Support Center
Hi Guys - The bottom line with this is that there hasn't been a human study done on the 'correct' dose of memantine. For that matter, there hasn't been a double-blind study on Mematine efficacy in HD at all. So there's two kinds of information out there: 1. Anecdotal clinical experience, just doctors who have some experience with certain doses 2. Mouse data from trials with diffeby jcarroll42 - Huntington's Disease Support Center
Hi Melissa, I'm not sure how technical you're interested in, but there's a very nice (free) review from Asa Peterson and Maria Bjorkvist at: Some of this might be overkill, but the facts are there. jeffby jcarroll42 - Huntington's Disease Support Center
Hi Krista, I work in a lab that has many thousands of DNA samples from HD patients. When we've looked for "stable" CAG sizes in families, we can't really find them. CAG changes on the order of 2-3 are very common, and changes as much as 6 (as you report) are not at all abnormal. There is research, which I'd be happy to send you if you like, that quantifies all this. But I donby jcarroll42 - Huntington's Disease Support Center
Hi Eve - First, with a CAG as low as 40, I think there is a lot of variability in the age of onset. The relationship between CAG size and age on onset gets stronger for bigger CAG's, but isn't as predictive for lower numbers (like 40). As for the other copy, 20 CAG's would be considered relatively low in the terminology of the studies I mentioned to you. The average CAG in normal copiesby jcarroll42 - Huntington's Disease Support Center
Hi Eve, There is an effect of the CAG size in the "normal" copy of huntingtin. The effect is somewhat complicated. For people with high mutant CAG's (>48 or so): a high CAG in the "normal" gene (20-30 CAG's) is associated with a later age of onset. This means that a higher "normal" CAG is actually a good thing. For people with low mutant CAG's (36-4by jcarroll42 - Huntington's Disease Support Center
Hi Judy - I'm not an MD. But, my understanding from the scientific literature is that the actual metabolic rate of HD patients is increased, on top of the effects of chorea. The PHAROS study has found, for example, that even "pre-symptomatic" mutation carriers eat more food, despite having a lower body mass index. So there may not be a 100% clear answer - but I think the evideby jcarroll42 - Huntington's Disease Support Center
Hi Diana - The weight loss is not just from lack of calories consumed. HD patients have higher metabolic rate - so they're burning more energy even if they're not doing anything. This is part of the reason it's so hard to keep weight on patients (in addition to the feeding difficulties). jeff Jeff Carroll Centre for Molecular Medicine & Therapeutics University of Briby jcarroll42 - Huntington's Disease Support Center
Hi Barb - I think in HD we are luckier than any most any other disease with such a small patient population. There is a trend towards drug company interest in "solvable" problems. HD is a good candidate for pharmaceutical/biotech interest because we can very easily identify patient populations, with 100% certainty. Compare this to Alzheimer's or Parkinson's disease, where the grby jcarroll42 - Huntington's Disease Support Center
Eric - Good point - clearly this work couldn't be used to, say, diagnose HD earlier. These are subtle effects. But I think its still important - it helps us see a suite of "symptoms" that occur before chorea. I think this reorganization of the way we think about HD is really important. jeffby jcarroll42 - Huntington's Disease Support Center