Maze Therapeutics recently announced it is starting a phase 1 clinical trial testing MZE001, a substrate reduction therapy in development to potentially treat late-onset Pompe disease.

MZE001 is an oral glycogen synthase (GYS1) inhibitor designed to reduce the accumulation of glycogen in Pompe disease.

The phase 1 study is a double-blind, placebo-controlled study testing the safety, tolerability, pharmacokinetics and pharmacodynamics, and food effect of MZE001 in healthy volunteers.

Recently, preclinical data were presented at the 18th Annual WORLDSymposium in San Diego, CA, supporting MZE001 as a treatment for Pompe disease. Some of the key takeaway data points from the preclinical data include:

  • MZE001 is a potent and specific inhibition of GYS1.
  • Displays dose dependent inhibition of glycogen synthesis with no effect on glycogen synthesis in the liver
  • Reduces the accumulation of glycogen in various tissues, including skeletal muscle
  • Shows good tolerability
  • When combined with enzyme replacement therapy there is a normalization of tissue glycogen and restored cellular homeostasis

In a news release, Sarah Noonberg, MD, PhD, chief medical officer of Maze Therapeutics stated, “This work demonstrates the potential value of our substrate reduction approach across the Pompe disease spectrum both as combination therapy and as monotherapy. We are excited to continue our efforts with this program as we advance MZE001 toward the clinic.”

Priya Kishnani, MD, of Duke University Medical School added, “I am encouraged by the preclinical data from Maze’s program targeting glycogen synthesis, which could potentially offer a new and complementary treatment option for these patients.”

To learn more about the clinical trial go to

Tagged: clinical trials, research, substrate reduction therapy