Hey Jeff, i have an idea, and just wonder what your thoughts might be on this. I wonder if this was to be tried on mice, what would happen. What if they took mice at dif stages of the disease, and try and find out, if the earlier the disease, or maybe the lower the cag count, that a lower dose of memantine might be needed, and the worse the disease, like later in the disease process, or, maybe the higher the cag count, that maybe more memantine could be needed. I guess what im wondering is, i wonder if, at dif stages of the disease, could earlier disease have less excess glutamate, and does the amount of excess glutamate increase as the disease goes on?

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 is a very good one.

The hard thing about this kind of experiment is that it's extremely time consuming and hard to run. If you can estimate that each group of mice needs to be about 20, you can do the math. There's always HD and control mice, so that's 40 mice per group. You always have to have treated mice and untreated mice, so now we're up to 80 mice for a single dose. If you want to do multiple doses, you need to add 40 mice per dose. Same logic for additional time points - 40 more mice for each additional time point.

Even with just one dose, a trial like this ends up costing about $100,000, by the time we analyze their behavior and brains. So it's not trivial to get enough money to address these kinds of questions.

At some point, we have to just say we've done all we can in the mice and do some experiments in humans. I'm not sure if we're there yet with Memantine, but Mahmoud and Michael (and others) are still working hard on it.



jeff

Thanks for explaining all that Jeff. It makes sense, but too bad it wasn't easier!