Is an Effective Bipolar Treatment Just Around the Corner? Depends How You Look At It ...
The purpose of this piece is to give you a sample of cutting-edge research into bipolar. My intention is to be impressionistic, rather than explicit. In other words, don’t feel you need to comprehend the technical fine points.
Last week, in San Diego, I attended the Exponential Medicine Conference, organized by Singularity University. One of the speakers was Evan Snyder, Program Director of Stem Cells and Regenerative Medicine at the Burnham Institute for Medical Research. One area of his research involves how neural stem cells self-renew and differentiate into neurons, astrocytes, and oligodendrocytes.
Astrocytes and oligodendrocytes are types of glia, cells that support neuron function. You can’t just grow stem cells to replace neurons. You also have to engineer for all that glia, as well.
Stem cells are a hot area of research in medicine. Already, replacement trachea, fashioned from 3D printers using a biological ink of stem cells, have been implanted into humans on an experimental basis.
The human brain, of course, is infinitely more complex than a windpipe, as are the many things that can go wrong. Mental illness, for instance, is “polygenic,” meaning its symptoms are influenced by more than one gene.
Perhaps you can see the problem: The best stem cell technology is of no use to anyone if we cannot find an appropriate target.
With regard to bipolar, the best strategy appears to be a “molecular can-opener.” I first came across this approach some 13 or 14 years ago with regard the research of Husseini Manji, then at the NIMH. We know, for instance, that lithium works on bipolar. Can we, in effect, pry into the can to reveal what is going on?
One of the targets of lithium appears to be CRMP2, a molecule inside the neuron, that, among other things, is important to dendrite development. Dendrites are the spiny projections from neurons that receive neurotransmitters from nearby axons branching out from other neurons.
Just to make this totally confusing, CRMP2 also supports axonal growth.
“Excitotoxicity” can interfere with the normal chemical processes of CRMP2. CRMP2 is getting phosphorylated too much. This means the biochemical “on-off” switch goes haywire, with disastrous downstream effects.
According to Dr Snyder, lithium appears to lower the level of phosphorylation. Animals high in CRMP2 gravitate to the center of the field, the area where you are most likely to be eaten (not a good thing).
“Now,” according to Dr Snyder, “we have a target. We think we know the pathway.”
Dr Snyder talked about finding the right drug to target CRMP2. This is a far cry from a stem cell fix, but the same organizing principle underlies every search for a treatment or cure or prevention, namely: “What needs fixing?”
I have been reporting on bipolar for 15 years, and I am far too cynical and jaded to even suggest that CRMP2 is the future. Basically, despite all the spectacular advances in brain science and molecular biology and genetics this millennium, we are still being treated with meds based on old technologies from a previous era, with no new-generation meds in sight.
As for stem cells to treat illnesses of the brain, we are decades away, if ever.
On the other hand ...
Another one of the speakers at the Exponential Medicine conference was Ray Kurzweil, Director of Engineering at Google and best-selling author of The Singularity is Near.
A few days ago, I began reading his book. Exponential growth, he says - what amounts to a nonlinear explosion - always starts off looking slow and linear. This happened with computer processing prior to Moore’s Law becoming obvious to everyone.
Not only that, exponential growth generates its own exponential growth, so when the big bang happens it comes at you a lot faster and harder than the best linear projections ever could have anticipated.
The first years of sequencing the human genome, for instance, proceeded at a pace that indicated the job would take thousands of years to finish. Indeed, the naysayers took great delight in pointing this out.
So - here is the question: Have my last 15 years reporting on the search for more effective bipolar treatments been depressingly linear, with no end in sight?
Or have I been observing the long flat beginning of an exponential growth curve that is about to be unleashed on us with spectacular unflatness?
Can’t wait to find out ...