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New Frontiers: Mabs and mRNA. Could these work for GDD?

Monoclonal antibodies (Mabs) have come to public attention as biologic drugs taken to specifically

attack the COVID virus, and mRNA are the basis of the currently released vaccines for COVID in the USA: by Pfizer and Moderna. So these have come into the public dialogue as being important and life-saving against the COVID-19 virus SARS-cov-2. The obvious question, what about other diseases, can they work for them. Probably yes, for every type of disease that somehow is in the rubric of an invader: from the outside, like infections (and Gd), or the inside, like cancers. The way Mabs are developed for COVID virus, they directly attack and neutralize the virus, and mRNA vaccines to get the host cells themselves to attack and neutralize virus.

In general terms, Mabs act on the surface of things - so the surface of viruses and surface of host cell membranes, whereas mRNA works as messengers (hence the m in MRNA) to the inside of cells, to their DNA so that the cells themselves are programed on the inside, to create substances that will do important things: like kill invaders. So Mabs work on the surfaces, mRNA on the inside. One could also consider, although not specifically done yet for COVID-19, wouldn't this combined outside and inside attack be even more effective. That sounds like an effective strategy.

Antibodies are like little bullets that certain members of our immune system, elaborate, primarily B-cells. Monoclonal means just one type of antibody, since our cells release hundreds of different antibodies that have the full range of effects, from killing viruses (neutralizing) to killing ourselves (uncontrolled cytokine storm). So in general our immune system has most of the time an intrinsic pattern of regulating and balancing reactions to everything: from strawberries to COVID, and much worse villains. Mabs as currently employed are injection of mature antibodies that have limited activity duration, just like one time injection of any drug, likely up to 3 days are the maximum effect.

mRNA basically is a substance that can modulate and change the function of the thinking central processing unit of our cells, the DNA. So it is quite an elegant process. It is like a messenger soldier on the battlefront take a note from high command to the battlefield general: assemble tanks and planes in this location, soldiers in this, to defeat the enemy. Same concept, and as with this hand-carried note it is still in the development phase for everything we would want attacked. So many things it is a hand-carried note (hence may or may not work), but for some where the investment has been made, more like a computer based system with arial satellites, computer 3D modeling of your and enemy forces, with 100s of simulations worked out, which is about where COVID is at. GDD and mRNA is currently no where, as not work is done on it, so it is not even a carrier pigeon with a note tied to its ankle. This does not mean we should not be optimistic. It also means we should be paying attention to developments in related fields, as the solution for GDD may be only a half step away in using the same approach.

mRNA can really act like a key to turn cell functions on or off. So for example with cancer, to turn the key for host immune cells, like T-killer cells, macrophages, and natural killer cells, to recognize cancers and kill them (which they presently are not doing because of the various tactics that cancer cells use to avoid detection), and the turn key for GDD would be as simple as turning the system off for T-cell, and other cells ,to react violently (releasing cytokines and other products) when they see Gd, so they just ignore them; perhaps another key for osteoclasts in bone to kick Gd out of bone; and another key for renal glomerular and tubular cells to increase their removal of Gd when they see it. These two latter keys acting like bouncers in a bar dealing with trouble-making drunks: kicking them out the door and telling them to never come back. Ofcourse a future step is mRNA to generate Mabs, so only mRNA necessary, and the Mabs would then have durability, which they currently lack.

In actuality we are probably only 3 steps away from using exactly what is being done for SARS-

cov- 2, with Mabs and mRNA for GDD, so we should be paying close attention, because the solutions may be nearly exactly the same. There likely will be other diseases between this virus and GDD, that will bring us even closer to the exact same Mabs and mRNA (1 or 2 steps away). Maybe this strategy for lead or for rheumatoid arthritis or lupus, will bring us to being on the one yard line for scoring a touch down with GDD treatment.

Richard Semelka, MD

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