Plus Chumplybum , great question.
I have simplified my thoughts on how NUZ-001 or Monepantel (S) ( both the same) is transformed in the body system. So lay people can understand, thus it's not truly academic , but I have tried to encompass most. I am isolating the disease ALS MND only for simplification.
NUZ-001 an oral small molecule drug is possibly metabolised by gut microbial or hormone regulation. No studies to confirm either way.
After metabolism in the gut, Monepantel turns into Monepantel Sulphone after 4 hours in the bloodstream.
When monepantel enters the body, enzymes in the liver add oxygen to the sulfur atom in its structure.
Once in the bloodstream the body adds an extra layer of oxygen to the partially oxygen enriched monepantel and it turns into Monepantel Sulphone.
This obviously takes time about 24 hours to hit a peak concentration.
The drug that then goes to work in the system, distributed mainly to tissues such as the liver, fat, and other tissues like muscle and the kidney.
Monepantel (S) then finds it was to the mitochondrial cells think of them as a nuclear power plant.
Remember Monepantel is a mTOR inhibitors ( chat later about that) so it slows certain pathways down.
The issue with ALS MND is an over reactive power plant that allows an increase of TDP43 to stick to the brains neurones causing a plaque issue ( think teeth ) . The neurones don't work as well due to the plaque. We then have motor dysfunction and subsequent brain interference.
Ok, the Monepantel Sulphone has joined with the mitochondrial cells. This is where it gets tricky. How so ? I have to go outside my scientific lense here to speculate as no studies show exactly how .
Inside the mitochondrial cells there is a delicate balance of voltage and chemical balances. Think a big dam feeding the power plant. All must be correct .
Mitochondria convert ADP (a low-energy molecule) into ATP (a high-energy molecule) using oxygen and nutrients. This is like turning raw fuel into usable electricity.
ADP is Adenosine diphosphate
ATP is Adenosine triphosphate .
So think of a diesel engine no spark plug. It relies on compression and fuel. So compression is blood pressure and fuel is a mix of ADP and ATP. We then have power to facilitate the mitochondria cell.
Ok , how does Monepantel (S) change things. We all know it's a inhibitor. So it slows down the overreactive nuclear power house.
Again it's gets back to how the mitochondrial cell interacts with Monepantel Sulphone.
We know in physics that a negative charge will repel a positive charge and likewise a negative charge will alike to a negative charge and vice versa.
Monepantel Sulphone to my thoughts is a neutrality charged particle that can slip either way.
Monepantel doesn’t directly "break" mitochondria but creates a chain reaction where stress and blocked pathways make it harder for the nuclear power plant to slow production and the related TDP43 plaque .
Ok to the crux. How does it do it ? This is where it gets scientifically tricky, my thoughts as no one has gone down this track yet.
Monepantel Sulphone alters the permeability of the mitochondrial membrane by affecting channels like ANT or VDAC.
VDAC (Voltage-Dependent Anion Channel) these are on the outer of the Mitochondrial cell. Monepantel Sulphone may influence VDAC's gating mechanism, altering its ability to stay open or closed. This can disrupt metabolite exchange, affecting energy production and cellular metabolism.
ANT (Adenine Nucleotide Translocator) is located in inner of the mitochondrial cell and facilitates ATP/ADP exchange during cellular respiration. Monepantel sulfone might interfere with ANT's function, potentially leading to reduced ATP synthesis or altered energy balance within cells.
This increased permeability might cause a "leak" in the membrane potential, reducing the driving force for ATP synthesis and lowering the ATP/ADP ratio. Thus reducing power to the nuclear plant.
Monepantel Sulphone could interfere with proton pumping or gradient maintenance, reducing the efficiency of ATP synthesis and altering the ADP/ATP ratio. Think pH ratio.
One may ask how does Monepantel Sulphone actually link up with the mitochondrial cell?
Maybe, it doesn't link as in join but it's molecular structure allows it to integrate more than link. Imagine loosely having oil on your fingers . Yes it doesn't cross the skin barrier but it affects your ability to complete the tasks. In this situation we are wishing for a slow down of a runaway body pathway.
How does Monepantel Sulphone affect the clean up of the plaque on the brain neurones?
Our cells have a natural cleanup system called autophagy, which works like a recycling program. It helps get rid of damaged parts, waste, or unneeded materials in the cell.
Now, there's a protein called mTOR (short for "mechanistic target of rapamycin") that acts like a "growth manager." When mTOR is active, it tells the cell to focus on growing and building new materials. However, when mTOR is active, it also blocks autophagy—essentially saying, "Don't clean up right now; focus on growth."
What Monepantel Sulphone does is turn off mTOR's activity. By doing this, it removes the block on autophagy, allowing the cleanup process to start. This is like flipping a switch that tells the cell, "Stop growing for now and focus on cleaning up the mess." This cleanup process can help remove damaged parts of the cell and recycle them into useful building blocks.
Finally after it's done it's wonder it's excreted by the faeces 70% and urine 30%.
My novel idea of the method of action of Monepantel.
Kpax
(20min delay)