Clinical Evidence & Case Studies
Explore real-world clinical validation of ER stress modulation.
Applications to Treat Degenerative Diseases -Type 2 Diabetes as an example
In Type 2 Diabetes, pancreatic β cells and medications work together to regulate blood sugar. As β cell function declines over time, stronger medications are needed to maintain control. Conversely, improved β cell function reduces the need for medication.
Our approach involves using ERAD Modulators to lower ER Stress in pancreatic β cells, promoting cell protection and regeneration (ref). This enhances β cell mass and function by preventing damage from nutrient overload.
With better β cell function, patients may require fewer or no Type 2 Diabetes medications, reducing drug dependence.
The Technology -RFEA (Rapid Fluorescent ERAD Assay)
At Servo BioLabs, we use RFEA technology to identify ERAD modulators by analyzing how test compounds affect ERAD rates. In our method, a fluorescent marker is attached to a misfolded protein in the ER lumen. Initially, the marker shows a high anisotropy value due to the protein's large molecular weight and its interaction with molecular chaperones. This anisotropy value decreases when the proteasome breaks down the misfolded protein into amino acids in the cytosol.
This measurement captures the rate of retrotranslocation (the slowest step in the process) and reflects the overall ERAD activity.
TX-107:
The First Identified ERAD Modulator
As illustrated in the figure, RFEA (Rapid Fluorescent ERAD Assay) can detect how TX-107 accelerates the ERAD process within just 10 minutes. It also provides insights into how varying concentrations of TX-107 influence ERAD rates, enabling the estimation of optimal dosage levels. RFEA’s speed is a major advantage, and its efficiency will further improve with automation. This accelerated assay method has the potential to streamline the identification of drug candidates for diseases such as diabetes, Alzheimer’s, and Parkinson’s.
Preclinical Trials
Studied in the lab. Clinically validated in humans.
TX-107 Accelerated the Degradation
of Misfolded Proinsulin
One of our key findings is the identification of TX-107, which has been shown to activate ER-associated degradation (ERAD) in β-cells. As illustrated in the figure, TX-107 significantly accelerated the degradation of misfolded proinsulin (lanes 4, 5, 6 vs. lanes 12, 13, 14) without affecting normal proinsulin stability (lanes 1, 2, 3 vs. lanes 9, 10, 11). These results demonstrate that TX-107 alleviates ER stress in β-cells, highlighting its potential as a promising drug candidate for the treatment of Type 2 diabetes.
TX-107 Accelerated the Degradation of Misfolded Proinsulin
One of our key findings is the identification of TX-107, which has been shown to activate ER-associated degradation (ERAD) in β-cells. As illustrated in the figure, TX-107 significantly accelerated the degradation of misfolded proinsulin (lanes 4, 5, 6 vs. lanes 12, 13, 14) without affecting normal proinsulin stability (lanes 1, 2, 3 vs. lanes 9, 10, 11). These results demonstrate that TX-107 alleviates ER stress in β-cells, highlighting its potential as a promising drug candidate for the treatment of Type 2 diabetes.
ERAD Modulators Help Delay or Reverse the Progression of Type 2 Diabetes
The pilot study highlights the effectiveness of ERAD modulators in improving diabetes management. In the control group, which continued standard prescriptions, only 9% of participants achieved improved blood sugar/A1c in Stage 1, 15% showed improved prescription durability in Stage 2, and just 2% reduced or ended their dependence on prescriptions in Stage 3. In contrast, the ERAD group, which received standard prescriptions supplemented with ERAD modulators, demonstrated significantly better outcomes: 79% improvement in Stage 1, 63% in Stage 2, and 25% achieving reduced or ended prescription dependence by Stage 3. These results emphasize the potential of ERAD modulators as an innovative treatment approach.
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