Protecting Memory After TBI and in Alzheimer’s – New Hope from 15-PGDH

So, you know, Andrew, for a lot of our listeners, we know that amyloid and tau is really important.

but there's so much more to the brain.

There are 100 billion neurons, but there are 100 billion astrocytes, oligodendrocytes, and microglia, and there's this thing called the blood-brain barrier.

So tell us from a brain science standpoint, is Alzheimer's an inflammatory disease? Are there common mechanisms where you would think something that worked in colitis? could work in Alzheimer's.

Tell us about new ideas of the pathogenesis of Alzheimer's that this thing could actually work.

Well, in terms of new ideas about the pathogenesis of Alzheimer's, it's becoming pretty well recognized that there are a number of different secondary processes that really drive the disease forward, particularly at the stages where people start to have symptoms.

And some of those processes are things like narrow inflammation.

Another one is decreased neurogenesis in a region of the brain called the hippocampus.

Hippocampus is really important for learning and memory and emotional, assigning an emotional value to the things that we learn and for navigating our day-to-day experiences over the course of our lifetime.

And Sandy's work had shown that inhibiting this enzyme helped support the health of stem cells in the colon.

And that was what made us wonder, well, what if this could also help support stem cells in the brain? And the hippocampus is one of the few regions of the brain that makes new cells from stem cells that reside.

And so that was really the flyer, if you will, that we took was we wondered, well, if it's helping in this other part of the body with this type of cell, might it also be helpful in the brain? And so that was a pretty straightforward thing to test.

We administered Sandy's compound to mice and showed that it got into the brain.

And then we saw that it was increasing not the proliferation of those stem cells, but it was actually increasing their survival.

So normally they're made and they die at a certain rate.

And when we gave the mice Sandy's compound, they were surviving at a much higher rate.

And so that was one of the most exciting things that we found early on that gave us a clue that this could have an important role in the brain.