Clinical Trials
PLL THERAPEUTICS
Best combination of compounds defined
PLL Therapeutics’ approach is based on the following principle :
- Active molecules are linked to Poly-L-Lysine (PLL) which increase their bioavailability and thereby their systemic availability to exert their activity and/or cellular uptake
- Poly-L-Lysine was selected among other bioavailability enhancers as it may, by itself, have beneficial properties
Based on the carrier properties of Poly-L-Lysine, we have developed PLL-001, a multifunctional therapy that has demonstrated a breakthrough potential to treat ALS in preclinical studies. PLL-001 is composed of APIs known to be effective against ALS’ neuro-inflammatory and neurodegenerative pathological pathways and to restore the intestinal epithelium barrier.
More on PLL-001 therapy targets
A multi-targeted approach is needed for this multifactorial disease
PLL-001 aims to counterbalance the multiple cellular metabolic defects of ALS and their consequences on motor-neurons, including:
- ROS (Reactive oxygen species)
- Glutamate
- Inflammatory mediators
- Amino acids
- Gut mucosal permeability
PLL-001: mechanism of action
ALS is a multifactorial disease and below we present the origins and the path that can lead to contracting it.
This pathway is valid also for other neurodegenerative diseases such as Parkinson’s, Alzheimer’s or autoimmune diseases such as multiple sclerosis, etc.
Factors that can TRIGGER the disease:
- Food
- Medication
- Infection (Fungi, bacteria or virus)
- Stress
- Auto-Immune disease
- Environmental toxins (Pesticides, chemicals…..)
- Low level in Vit D
- Genetic SOD1….
- The first 1000 days after birth (antibiotics,) with a microbiome impact
Factors that can create CHRONICITY
The chronicity factors are multiple but are present, non-random factors that will be at the origin of the deleterious processes maintained.
external environments —-> Mucosal interface —–> Internal environment The factors are multiple, some are occasional others are already present. For example, the microorganisms that live on our mucosal membranes.
API (Active Pharmaceutical Ingredient)
The types of API (Active Pharmaceutical Ingredient) – PLys products – being referred to in the different sections
The Intestine is clearly at the origin of such disease, even if 5 to 10% of the ALS population has a genetic root-cause, such as the well-known gene SOD1. During our preclinical studies, we did show that SOD-1 G93A mice had a disturbed intestinal microbiome.
In terms of drug effect, the target is clearly to restore the intestinal epithelium barrier and avoid large leakage.
Small Chain Fatty Acids (SCFAs) promote the maintenance of the tight junction between the enterocytes. To maintain the homeostasis of the gut as well as the pH, SCFAs, such as acetate and lactate, are pivotal.
Unlike propionate and acetate which move more easily into the blood, butyrate is mainly metabolized in the colon. A small portion will pass into the blood and play an important role in the permeability of the BBB.
The 4 mains SCFAs are: Butyrate, Propionate, Acetate and Lactate
They are mainly produced by gut bacteria (weak bacteria that are more sensitive). So, in the case of breaking homeostasis by pesticides or SOD1 familial forms or food, bacteria stop producing these SCFAs and dysbiosis starts with all its detrimental effects.
Therefore, our technology links to a specific polymer, PLys (Poly L Lysine), as a carrier to transport these SCFAs in the body, focusing on the gut and the BBB to restore normal gut integrity.
We show that PLL-001 had a significant dose effect in our previous clinical trial in multiple sclerosis (MS), as well as in our preclinical study on our SOD-1 G93A mice.
Our target, in terms of dosage of PLL-001, is to restore the same quantity of SCFAs as in healthy people.
Our PLL-001 5x will restore around 5 to 6 µmol/L of Butyrate in the blood which is very close to the requirements of around 3µmol/L for a heathy patient.
The role of our 4 SCFAs
Mechanism of Action: Overview of PLL 001
