Sunday, December 6, 2009

Going mano a mano with vaccines against non-infectious disease

Many chronic conditions now thought to be due to passive (genetic) rather than active environmental exposures may turn out to be due to infection, or to somatic changes of various kinds that build up with age.  Many of the chronic disease candidate genes identified by genomewide association studies (GWAS) and other approaches seem to relate to immune function or 'inflammation', whatever that may include (e.g., recent schizophrenia results)  Autoimmune diseases also may involve exogenous pathogens. 

Progress in vaccine production research may bring a host of infectious diseases under preventive control (see our "getting the bugs out" post)--and this would be preventive with respect to infection-related chronic diseases, as well. Here it's molecule against molecule--antigen against antibody in a molecular mano a mano combat.

But the same ideas may actually apply even more broadly. As we discuss at length in our book, life is about molecular recognition. In the case of infectious disease, it's molecules on bacteria and viruses that the immune system recognizes. But even most non-infectious diseases involve undesirable molecular recognition problems (too much or too little signal molecule or response to it, for example). Networks of interacting gene products (protein and RNA-based) are being identified.

Malfunctioning networks become dangerous if they affect too many cells, such as cells early in development that are the ancestors of major segments of the celllular/embryological descent tree that makes major organs. Thus, one mutant liver-precursor cell could have devastating effects, while the same mutation occurring in a cell in a mature liver will have no discernible effect (because the rest of the liver cells will be normal).

In complex non-infectious diseases, signaling malfunctions can amplify if a cell or set of cells produces too much or too little signal, it can induce other nearby cells to start doing the same or at least start hyper- or hypo-responding. Some traits, like epilepsies, may amplify from a single or small number of cells in this way. Many other diseases may be similar in this regard, such as diabetes or hormone-dependent diseases in which signal or receptor concentrations may be off-level.

To date, we're much better at treating infection than we are genetic diseases, but targeting a genetic network in some molecular-recognition way may be an eventual treatment approach to such complex diseases. If, as must usually be the case, the disease involves some sort of molecular misbehavior, some kind of nanochip, say, to test relative levels of various molecular components may be able to detect something going wrong. If the effect circulates so that the nano-detector 'sees' it, then perhaps some antibody-like 'vaccine' can target the protein that is produced in excess, bringing its level back to within safe limits.

So here could, at least in principle, be a way in which we can meld infectious disease strategies and network or systems biology concepts, to provide detection and treatment of complex diseases. To do that, individual genotyping would not be needed; all we would need would be a micro-implant that could detect component (or even sets of components) levels that were out of health range.

This may be dreamworld thinking at present, but it is not a stretch to think that infectious disease approaches rather than 'genetic' approaches (in the sense of inherited variation) will lead the way to major health advances (assuming we can afford them!).


Arjun said...

In taking an infectious disease approach rather than a genetic approach do you mean so as to sidestep 'gene for' tactics and thinking, or is that implicit in your recommendation to target genetic networks?

Ken Weiss said...

It's neither, I'd say. It means one does not need to focus on 'gene for' in the sense of identifying specific genetic variants in each person that are causal. But it is genetic in the sense that biological function works by interaction among gene products. Many of those move and have their action between cells; this largely includes signal molecules that serve as ligands for receptors (i.e., what a receptor receives by binding to it).

So the thought is that, like the immune system that patrols the intercellular spaces (like the blood stream) for foreign objects, one might monitor the relative levels of signals and other similar kinds of molecules, and use exogenous (introduced) immune-like molecules to adjust the levels of these things--for example by binding signals that are in excess so they can't reach their receptors.

As to networks, networks are essentially patterns of such interactions. Many occur within cells, and these could be harder to target (though there are immune-related ways to do that, too). But some aspects of most if not all networks work between cells.

It's just a thought.