TargEDys founders, Professors Déchelotte and Fetissov studied and described different metabolic pathways involved in appetite regulation through the microbiome-gut-brain axis. They focused especially on the satiety hormone alpha-MSH and its antigens.
As part of their research, they identified a microbiota-produced metabolite involved in the regulation of appetite: Caseinolytic peptidase B (ClpB).
This bacterial protein presents a similarity of sequence and structure to the satiety hormone alpha-MSH.
ClpB is able to connect to alpha-MSH receptors, activating the a-MSH pathways of satiety: this is molecular mimicry.
Hafnia alvei HA4597 increases fecal and plasmatic ClpB levels compared to placebo in Ob/Ob hyperphagic and high-fat diet mice – two models of obesity.
Hafnia alvei HA4597 significantly reduces overall weight gain in hyperphagic mice on a high-fat diet, and improves glycemia levels compared to the high-fat diet and to the Orlistat group.
Supported by pre-clinical results confirming the mechanism of action and showing positive results on weight management, TargEDys performed a 3-months clinical study at pharmaceutical standards on 230 overweight people.
Significantly more subjects lost at least 3% of baseline body weight at 12 weeks in the treated group compared to the placebo group (HA4597: 57.7% vs. Placebo: 41.7%; p=0.028).
The treated group felt a significant increase in fullness at 8 weeks (p=0.009) and 12 weeks (p=0.006) versus baseline and compared to the placebo group at 12 weeks (p=0.009). The treated group shifted from feeling hungry (<50% fullness) to feeling full during the study despite the hypocaloric diet.
The benefit was rated as “very good” or “good” by 68% of subjects in the treated group compared to 53% of subjects in the placebo group (p=0.019).